Human Physiology: An Integrated Approach with Interactive Physiology [3 ed.] 0131020153, 9780131020153

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THIRD EDITION

AN INTEGRATED APPROACH

Dee Unglaub Silverthorn

Word

Top Ten Ways to Succeed in Classes that Use Active Learning

Roots for Physiology

a- or an- without; absence

hypo- beneath or deficient

anti- against

inter-

ase signifies an

auto

By Marilla

Svinicki, Ph.D., Director

bi

University of Texas Center for Teaching Effectiveness

Make

the switch from an authority-based concep-

tion of learning to a self-regulated conception of learning. Recognize

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and go beyond what

cardio- heart

lipo- fat

cephalo- head

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cerebro- brain

contra- against

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sented in class or the text.

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inside of a hollow tube split apart

macro-

or rupture

large

micro- small

mono- one multi- many myo- muscle

de- without, lacking oligo-

^\

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See errors as opportunities to learn rather than ures.

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o o fl

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a guess.

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in the spirit of learning rather

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Human ^

Physiology AN INTEGRATED APPROACH THIRD EDITION

Dee Unglaub Silverihorn, Ph.D. University of Texas - Austin

WITH

William C. Ober, M.D. Illustration Coordinator

Claire

W. Garrison, R.N. Illustrator

Andrew C.

Silverthorn, M.D.

Clinical Consultant

WITH CONTRIBUTIONS BY

Bruce

R.

Johnson, Ph.D.

Cornell University

e PEARSON Ber\jamin

Cummings San Francisco Boston

New York

CapeTbwn HongKong London Madrid MexicoQty Montreal Munich

Paris

Singapore Sydney Tokyo Toronto

Publisher: Daryl

Fox

Executive Editor: Leslie Berriman

Development Manager: Claire Brassert

Development

Anne

Editor:

A. Reid

Associate Project Editor: Ziki Dekel Editorial Assistant:

Michael Roney

Executive Producer: Lauren Fogel

Media

Project Editor:

Kim Neumann

Art and Design Coordinator: Melissa

Photo Researcher: Travis Text

Morgan

Amos

and Cover Design: Jim Gibson

Production Coordination:

Elm

Street Publishing Services, Inc.

Compositor: Prepare/Emilcomp

Manufacturing Buyer: Stacey Weinberger Executive Marketing Manager: Lauren

Cover Photo: Henry

S.

Harp

M.D.

Lucid,

Credits can be found on page 878.

ISBN 0-8053-5957-5 Copyright

© 2004

Pearson Education,

San Francisco,

CA

Manufactured

in the

94111.

Inc.,

publishing as Benjamin

Cummings, 1301 Sansome

St.,

All rights reserved.

United States of America. This publication

is

protected by Copyright and

permission should be obtained from the publisher prior to any prohibited reproduction, storage in a retrieval system, or transmission in

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Library of Congress Cataloging-in-Publication Data

Silverthorn,

Human

Dee Unglaub, 1948-

Physiology: an integrated approach

/

Dee Unglaub Silverthorn; with William C.

Ober, illustration coordinator, Claire W. Garrison, illustrator, clinical consultant; p.

with contributions by Bruce

R.

Andrew

C. Silverthorn,

Johnson,

cm

Includes index

ISBN 0-8053-5957-5 1.

Human

(alk.

physiology.

paper)

1.

Title

QP34.5.S55 2004

612—dc21 2 3 4 5 6

7—VHC—07

e PEARSON Bor\jamin

Cummings

www. aw -Ik

.umii

2003052278

06 05 04

E.

Lake

Contents

in Brief

PREFACE

IX

mnammmm

i

Atoms,

w-

Cells

k-

Cellular Metabolism

Ions,

and

and Molecules

Tissues

*• Membrane Dynamn

^ ^T

Cardiovascular Physiology

J^

fi/oocf

Introduction to Physiology

^

Communication,

s

20

Blood

523

50

Mechanics of Breathing

546

84

Gas Exchange and Transport

574

124

The Kidneys

598

171

Flunl

Integrative Physiology II: and Electrolyte Balance

625

Introduction to the Endocrine System

^ ^y

4

2

Metabolism, Growth, and Aging

Homeostasis and Control

>

F/ow And the Control

490

UNIT UNIT

448

of Blooa Pressure

Integration,

and Homeostasis

3

Integration of Function

Basic Cell Processes: Integration and Coordination

»

UNIT

and Network

Properties

Digestion

659

^

Metabolism iind Energy Balance

695

208

Neurons: Cellular

T^

239 Endocrine Control of Growth

The Central Nervous System Sensory Physiology

284

and Metabolism

726

The Immune System

751

321 Integrative Physiology

Efferent Division: Autonomic anil Somatic Motor C ontrol

Muscles

^

Exercise

Reproduction and Development

782

796

389

Integrative Physiology

Control of Body

369

III:

I:

Movement

428

APPENDIX

A: Physics

APPENDIX

B:

APPENDIX

C: Anatomical Positions of the

and Math

835

Genetics

GLOSSARY [ND]

\

838

Body

842 843

CREDITS ill

About the

and

Art Coordinator as

Illustrators

an undergraduate

Illustrator at

DR. WILLIAM C.

OBER

studied

Washington and Lee University and ob-

tained an M.D. from the University of Virginia in Charlottesville. In addition to his medical school education, he studied in the

Department of Art

as Applied to

is

at

Johns Hopkins Uni-

Ober completed training

versity. After graduation, Dr.

dent in family practice. He

Medicine

now an

as a resi-

instructor in the Division of

Sports Medicine at the University of Virginia. During the sum-

About the Author

mer, he teaches biological illustration at Shoals Marine Laborato-

DEE UNGLAUB SILVERTHORN dergraduate in

at

Tulane University and went on to earn

marine science

search interest

is

at

a

Ph.D.

the University of South Carolina. Her

in her labora-

on transport properties

of the chick

membrane. She began her teaching

ry,

where he

career in the

is

part of the core faculty. Dr. Ober's professional

now focuses on

re-

and work

epithelial transport,

tory currently focuses allantoic

studied biology as an un-

medical and scientific

and

Mary Baldwin

College, she

1986. Ms. Garrison

Carolina but over the years has taught a wide range of stu-

The

from medical and college students to those

prepar-

still

ing for higher education. At the University of Texas she lectures

in

physiology, coordinates student laboratories in

physiology, and instructs graduate students in a course

veloping teaching

skills in

the

life

sciences.

on

de-

She has substantial

experience with active learning in the classroom and has given

workshops on

this subject at regional, national,

tional conferences. in

Dee

Physiology Education

of the

is

currently editor-in-chief of Advances

American Physiological

Union

improve physiology education ,i

member

of the

Society.

in

She works with

mem-

College Sc ience Teaching.

media

fiber art

Her

tree

is

Physiology Society,

time

and enjoying the Texas

is

and the

Societx fol

spent creating multi-

hill

by

Dr.

member

at Shoals.

Ober and Ms. Garrison have won following: Asso-

for Art

and Design); Printing Industries

of America (Award of Excellence); the Society of

Authors (Talbot

Prize)

Academic

and Bookbinders West. They have also

received the Art Director's Award.

About the ANDREW

C.

country with her

Clinical

Consultant

SILVERTHORN, M.D.

practice in Austin, Texas.

Academy (West

nam, and upon

husband, Andy, and their three dogs.

iv

Book Clinic (Award

developing countries. She

ciation for Biology laboratory Education,

also a core faculty

ciation of Medical Illustrators (Award of Excellence); Chicago

Military

Human Anatomy and

Dr. Ober's associate in

numerous awards from groups including the

of Physiological Sciences to

the Society for Comparative and Integrative Biology, the Asso-

(

texts illustrated

is

became

from

interna-

and past-chair of the Teaching Section

bers of the International

also

and

make med-

obstetric nurse. After receiving a degree in art

Physiology Department at the Medical University of South

dents,

to

her career after almost two decades as a pedi-

ical illustration

atric

illustration.

CLAIRE W. GARRISON chose

Illustrator

life

He

is

a

is

a physician in private

graduate of the United States

Point), served in the Infantry in Viet-

his return entered medical school at the

Medical

University Of South Carolina in Charleston, lie completed his

family practice residency

Branch, certified is

(

lalveston,

at

the University

where he was duet

by the American Board

ol

ol

Texas Medical

and he

resident,

Family Practice.

is

board-

When

\nd\

not busy sccmg patients he maj he found on the golt course,

playing golf or running witi his chocolate

lab.

l

>n\\

Godiva.

Owner's Manual: How to Use This Book Welcome

Human

to

Physiology!

As you begin your study of the pared to make

maximum

human body, you

should be pre-

use of the resources available to you,

including your instructor, the textbook.

library,

One

of

my

the Internet, and your goals in this

book

to

is

provide you not only with information about

how the human body functions but also with tips for studying and problem solving. Many of these study aids have been developed with

the input of find

them

On

my students,

so

I

think you

may

particularly helpful.

the following pages,

I

have put

to-

gether a brief tour of the special features of

the book, especially those that you

have encountered previously

may

not

in textbooks.

Please take a few minutes to read this sec-

you can make optimum use of the text as you study. If you take advantage of features such as the Concept Checks, the Figure and Graph Questions, and Running Problems, you will find that you begin to think about phystion so that

iology in a different way.

One

of your tasks as

you study

yourself a global view of the body,

will

its

be to construct for

systems,

and the many

processes that keep the systems working. This "big picture"

is

what physiologists call the integration of systems, and it is a key theme in the book. In order to integrate information, however, you must do more than simply memorize it. You need to truly understand it and be able to use it to solve problems that you have never encountered before. If you are headed for a career in the health professions, you will do this in the clinics. If you are headed for a career in biology, you will solve problems

in the laboratory,

field,

or classroom. Analyzing,

and evaluating information die skills that you develop while you are in school, and hope that the of this book will help you with this goal.

synthesizing,

need to features

Good

I

luck with your studies!

Warmest

regards,

Dr.

[email protected]

Dee

(as

my

students

call

me)

ANATOMY SUMMARIES

CHAPTER OUTLINE Each chapter begins with an outline for that chapter.

You

major headings

listing the

page reference next to each

will find a

heading. Use this outline to preview the chapter before you

Do you

start reading.

see

any connections between these topics

and concepts you have learned

in previous chapters or other

courses?

To understand physiology, you must also have

a

good under-

standing of basic anatomy. This book includes several

Anatomy

Summary

of a phys-

figures that help

from

iological system,

move all

a

way down

to see

all

visualize the

anatomy

to micro perspective. As

components

across the figure,

the

you

macro

you

of a structure are enlarged,

to the tissue level. These

summaries allow you

of the essential features of each system in a single

fig-

ure, either as a review or for the first time.

BACKGROUND This handy

list

BASICS

at

the beginning of each chapter shows you

FOCUS ON ORGAN FIGURES

which important concepts you should have mastered prior to beginning the chapter. If any of these topics seem unfamiliar, use the page references to revisit the subjects you need to review.

anatomy and physiology looked in physiology

of organs that are often over-

including skin, the

texts,

liver,

and the pineal gland.

FIGURE

CONCEPT LINKS

®

There are several large focus features highlighting the

AND GRAPH QUESTIONS In

These encircled "chain-links" with page references are an extension of the Background

Basics, linking

concepts discussed earlier in the find material that

you

new

help you inter-

and apply concepts,

FIGURE QUESTIONS

ber

you might have forgotten or that might be

helpful for understanding

effort to

pret quantitative information

to

They help you

text.

an

of

figures

a

num-

and graphs

throughout the book include

concepts.

questions that ask you to consider what you really

know about

the information you have just encountered. Answers to Figure

FIGURE REFERENCE LOCATORS The colored each figure ing

it

circles

in the text

easier for

and Graph Questions appear

found next to the

first

function as place markers, mak-

you to toggle between an

and the running narrative associated with that

at

the end of every chapter.

reference to

illustration

illustration.

FOCUS BOXES You

will find three

kinds of small boxes in this book. All of

these boxes were developed with the goal of helping you un-

derstand the role of physiology in science and medicine today:

CONCEPT CHECKS These breaks

in the text,

placed at intervals throughout each

chapter, act as stopping points

where you can check your un-

derstanding of what you have

just read.

Some

you to think about or apply

what you have learned. Answers

to the

REFLEX I

Concept Check ques-

end of each chapter.

he reflex pathways and concept maps organize material into a

their

format that links both physiological themes and

supporting

schematic or

accounts

oi

derstanding

details

a blueprint,

into

a

unified

reference.

I

ike

a

concept maps pto\ ide detailed visual

systems and processes and guide you to ot

moving world

coordinated physiological function.

r F

of biotechnology.

CLINICAL boxes

on

focus

clinical

and

applications

pathologies. In addition to being interesting, these

boxes

help you understand homeostasis and nor-

will

mal function.

PATHWAY AND CONCEPT MAPS

logical, visual

boxes discuss physiology-related

applications and laboratory techniques from the fast-

of these ques-

tions are factual, while others ask

tions appear at the

NKW- BIOTECHNOLOGY

a better (

olors

un-

and

EMERGING CONC1

IMS boxes give you

a

glimpse into

new and exciting developments In physiological research. Some topics, such as stem cells, that were high-

lighted in

Emerging Concepts boxes

become fundamental concepts of the main text.

In

in earlier editions

physiolog) and are

have

now

part

shapes are used to key different processes and properties inside the maps. Foi example, the stimulus 01 starting point a

yellow oval, while the Integrating center

is

always

Is

An additional

always

a red dia-

mond. Ybu will learn to create youi own maps by completing the mapping questions found in the end-of-chaptei exercises.

DIABE ol

MS

human

I

111 \ll

feature to .

Which

physiology.

Biotechnology box,

a

\ c

is

all

three ot these locus boxes

is

a

used to illustrate the comple\it\

diahetes linical

theme box

bears the icon ot a

box, or an Emerging Concepts

on the information presented. Because it makes a

box, depending

widespread effect on the body,

betes has such a

dia-

END OF CHAPTER QUESTIONS

per-

The end-of-chapter questions have been organized into four learning levels to allow you to develop your problem-solving

example of integrated physiology. Some boxes explain the effects of diabetes and then show how the body must compenfect

sate to cal

maintain homeostasis. Others describe biotechnologi-

advances or breakthroughs in the treatment of diabetes.

skills

through

a logical progression of exercises

to conceptual to real-world to quantitative.

—from factual

Answers to Level

One, Two, and Three questions can be found on the companion website. Answers to Level Four questions appear at the

end of the chapter. Level One questions review

RUNNING PROBLEMS

OEach

chapter includes a relevant,

real-life

problem that

appears in segments throughout the chapter. After the

opening scenario

established, segments

on

ly

Level

concepts.

prompt you

to utilize information

you have learned. Use

Two questions

test

your

Level Three exercises are real-world scenarios designed to de-

velop your problem-solving

segment of the problem.

dealing with Level Three questions

check your problem-solving strategy against the Problem Conclusion,

which

lists

the questions from each segment, the

steps that were required to successfully analyze

and analysis"

the running problem.

(or to

Facts:

this

a question

check your solution), examine the Facts and Integration

and Analysis columns

first

skills.

two

You

levels.

you can go

be more successful you have successfully

will

if

To check your answers or

to the book's website.

Level Four questions are quantitative

ing or

some mathematical manipulation. To

swer Level Four questions, you must

first

and the concepts and then be able

vant data to develop at

and require graph-

to

successfully an-

understand the

manipulate

a quantitative picture of

rele-

the physiology

hand.

to the right of each question.

As you study the chapter, identify relevant facts from

and from

earlier chapters.

Use the

check

facts listed here to

Integration

and

Analysis: As

you work through the chapter,

try to analyze the information you've learned to arrive

at

an an-

Using the explanation under Integration and Analysis,

check to see

if

your reasoning

is

sound.

that highlights the physiological

in the chapter.

a narrative

paragraph

themes encountered

in the

followed by enumerated points and page

ences, providing

you with

the end of each chapter following the chapter exercises,

ranging from print and sites.

media

sources,

online journals to magazines to Internet

Each Exploration examines topics relevant to the chapter ma/

s

Myelinated Vxons

260

.

Contents

^ •

Biotechnology:

Electrical Activity

Mutant Mouse Models

Can Be

jj^ Biotechnology:

Of Snakes,

Cell-to-Cell

•

Is

and Run

264

of Neurotransmitters

265

^

266

Clinical Focus: Myasthenia (iravis

267 268

Neurotransmitter Activity Is Rapidly Terminated

Long-Term Potentiation

•

•

The Cerebrum

268 271

Development of the Nervous System Depends on Chemical Signals

297 297

298

the Site of Higher

299

The Cerebrum Has Distinct Regions of Gray and White Matter Chemical Communication Influences

299

Neural Pathways

300

he

(

erebral Cortex

301

Organized

Is

into Functional Areas

302

274

Sensory Information Is Integrated in the Spinal Cord and Brain

302

Sensory Information

Is

Processed

304

into Perception

When

Chapter

296

273

274

Neurons Are Injured, Segments Separated from the Cell Body Die

295

Brain Functions

I

Diseases

Is

Brain Function

Alters Synaptic

Many

295

The Diencephalon Contains

Disorders of Synaptic Transmission

Are Responsible for

294

The Brain Has Six Major Divisions The Brain Stem Is the Transition Between Spinal Cord and Midbrain Anatomy Summary: The Brain The Brain Stem Consists of Medulla, Pons, and Midbrain The Cerebellum Coordinates Movement

Many

Communication •

293

268

Synaptic Activity Can Be Modulated at the Axon Terminal

292 293

268

Neural Pathways May Involve Neurons Simultaneously

292

the Brain

the Centers for Homeostasis

Integration of Neural Information Transfer

291

Barrier Protects the Brain

The Spinal Cord The Brain

264

Not All Postsynaptic Responses Are Rapid and of Short Duration

•

JT

Secretes a Variety

•

•

Fluid

290

Clinical Focus: Diabetes —Hypoglycemia

and

Neurocrines Convey Information

The Nervous System

Fluid

in the Blood Nervous Tissue Has Special Metabolic Requirements

Emerging Concepts:

Multiple Receptor Types Amplify the Effects of Neurotransmitters

•

•

263

•

•

•

The Blood-Brain

263

from Neurons to Other Cells •

•

the Signal for Neurotransmitter

Synaptic Vesicles Kiss •

Anatomy Summary: Cerebrospinal

288 289

from Harmful Substances

Release at the Synapse

^

•

263

Information Passes from Cell to Cell at the Synapse

Calcium

262

•

Anatomy Summary: The Central Nervous System The Brain Floats in Cerebrospinal

Communication

in the Nervous System •

261

•

Snails, Spiders,

and Sushi •

•

Altered by

Chemical Factors

a Variety of

Bone and Connective Tissue Support the Central Nervous System

261

The Motor System Governs Output

Summary

275

from the Central Nervous System

277

304 305

Questions Explorations

279 281

The Behavioral State System Modulates Motor Output The Reticular Activating System Influences

Answers

282

States of Arousal

-504

Physiological Functions Exhibit

The Central Nervous System £$ Running • •

Problem: Infantile Spasms

Emergent Properties of Neural Networks Evolution of Nervous Systems

^ •

284

•

The Central Nervous System Develops from a Hollow Tube The Central Nervous System Is Divided into Gray and White Matter

.

.

.

.

Why Do We Sleep?

307

f?

285

^ and That

286

.

306

284

Clinical Focus: Sleepwalking

Emerging

285

Biotechnology: Tracing Neurons in a Network

Anatomy of the Central Nervous System •

.

Orcadian Rhythms

•

287 •

(

'oncepts:

308

Adenosine

"Java jolt"

$08

Emotion and Motivation Are Complex Neural Pathways

$08

Moods

$09

Are Long-Lasting Emotional States

287

•

Learning and Memory Change Synaptic Connections in the Brain

287

•

Learning

Is

the Acquisition of Knowledge

309

Uo J47

• •

1

Efferent

Sympathetic and Parasympathetic Branches Exit the Spinal Cord in Different Regions

342

343

—A Powerful

•

Auditory Pathways Project to the Auditory

Running Problem: Nicotine

369

The Autonomic Division

343 first in

362

366

as Integrating

of

Inner Far

Sounds Are Processed

Summary

Addiction •

340

Ear

360

Autonomic and Somatic Motor Control

340

Ear:

357

Efferent Division:

Five

Basic Sensations

—A New Photosensitive Pigment ...

Signal Processing Begins in the Retina

335

337

a

•

333

Anatomy Summary: Is

Concepts:

367

336

Taste

357

Answers

Olfactory Cells Are Neurons Olfaction

Photoreceptors Transduce Light

364

333

One

356

Retina

Questions Explorations

Nociceptors Initiate Protective Responses

Is

353

the Retina

330

332

Olfaction

at

Chapter

Temperature Receptors Are Free Nerve Endings

^T" Clinical Focus: Pain Control

351

330

332

Chemoreception: Smell and Taste

350

Light Enters the Eye

JF Emerging

326

Different Stimuli

.

Protected by the Skull

Melanopsin

Many

Pain and Itching Are Mediated by Nociceptors

Is

into Electrical Signals

Information

to

Equilibrium Pathways Project Primarily

The Eye and Vision

into Graded Potentials

Touch Receptors Respond

349

•

Sensory Transduction Converts Stimuli

The Central Nervous System

Vestibular Apparatus

349

B21

Running Problem: Meniere's Disease

347

to the Cerebellum

319 •

347

The Adrenal Medulla Secretes Catecholamines

.

.

Most Sympathetic Pathwav s Sec icte Norepinephrine onto Adrenergic Receptors ....

376 377

Contents

•

•

•

Parasympathetic Pathways Secrete

378

Autonomic Agonists and Antagonists Are Important Tools in Research and Medicine Primary Disorders of the Autonomic Nervous

378

System Are Relatively

y Neuropathy Summary

•

Uncommon

Clinical Focus: Diabetes

•

•

Acetylcholine onto Muscarinic Receptors

379

of Sympathetic

•

381

A Somatic Motor Pathway of One Neuron

381

•

382

•

The Neuromuscular Junction Contains

Chapter

Summary

384

Quest ions

385

Explorations

387

Answers

•

389 390

Skeletal Muscles Are

Composed 391

Anatomy Summary: Organization of Skeletal Muscle

392

414

Smooth Muscles Are Much Smaller than Skeletal Muscle Fibers

414

Smooth Muscle Has Longer Actin and Myosin Smooth Muscle Contractile Filaments

415

Are Not Arranged in Sarcomeres

416

Phosphorylation of Proteins Plays a Key Role in Smooth Muscle Contraction

417

Relaxation in

Smooth Muscle 418

Calcium Entry Is the Signal for Smooth Muscle Contraction 2"

419

Muscle Stretch Opens Ca

Some Smooth Muscles Have Unstable Membrane Potentials Smooth Muscle Activity Is Regulated

419

by Chemical Signals

419

Channels

Cardiac Muscle

Chapter

of Muscle Fibers

Smooth Muscle

Atherosclerosis

•

•

•

Skeletal Muscle

Clinical Focus:

•

389

Running Problem: Periodic Paralysis

413

Has Several Steps

388

Muscles •

•

Consists

Nicotinic Receptors

412

and •

The Somatic Motor Division

Muscle Disorders Have Multiple Causes

f?

—Diabetic Autonomic 380

410

Smooth Muscle

379

and Parasympathetic Divisions

•

•

Bones and Muscles Around Joints Form Levers and Fulcrums

419

421

Summary

422

Questions Explorations

424

426 42~

Answers

Myofibrils Are the Contractile Structures

394

of a Muscle Fiber

Muscle Contraction Creates Force Muscles Shorten Contraction

When They

Contract

396

Integrative Physiology

396

Control of Body Movement

Regulated by Troponin

Is

and Tropomyosin

399 •

Biotechnology: The In Vitro Motility Assay

.

.

.

399

%# Running Problem: Neural Reflexes •

Acetylcholine Initiates Excitation-Contraction

400

Coupling

Muscle Fatigue

I

las

403

Tension Developed by Individual Muscle Fibers Is a Function of Fiber Length

.

.

A Motor Unit

Is

and the Muscle

It

Innervates

Contraction in Intact Muscles Depends on the Types and Numbers of Motor Units •

Mechanics of Body Movement Isotonic Contractions Move Loads,

430

430

Skeletal Muscle Reflexes

431

•

404

Muscle Spindles Respond to Muscle Stretch .... £7"

405

•

406

•

Clinical locus: Reflexes

•

Stretch Reflexes

and Reciprocal Inhibition

Movement Around

Flexion Reflexes Pull Limbs

a Joint

408

•

The Integrated Control of Body Movement •

408

•

Movement Can Be

436

Away

from Painful Stimuli

408

434 435

Muscle Tension

Control

407

and Muscle Tone

432

Golgi Tendon Organs Respond to

but Isometric Contractions Create Force

Without Movement

Visualization

Autonomic Reflexes

One Somatic Motor Neuron Fibers

429

•

Force of Contraction Increases

with Summation of Muscle Twitches

Classified

•

Skeletal

.

Can Be

.'

h\ hniques in Sports

401

Multiple Causes

Muscle libers Are Classified by Contraction Speed and Resistance to Fatigue

429

y* Emerging Concepts:

Muscle Contraction Requires Steady Supply of ATP

Skeletal a

Ways

428 42N

Tetanus

Neural Reflex Pathways Different

I:

436 438

Classified as Reflex

Voluntary, or Rhythmic

43S

The CNS

440

Integrates

Movement

XXV

CONTENTS Emerging Concepts: Central Pattern Generators and Spinal Cord Injuries

J??

•

Symptoms

The Heart Contracts and Relaxes Once

in Visceral Muscles

.

.

y

443 •

444

Questions Explorations

445

Answers

447

471

During a Cardiac Cycle

442

Summary

Chapter

•

Reflects the

Electrical Activity of the Heart

of Parkinson's Disease Reflect the

Movement

Control of

The Electrocardiogram

440

Functions of the Basal Nuclei •

•

Clinical Focus: Gallops, Clicks,

447

.

Cardiac Cycle

Volume Is the Volume of Blood Pumped by One Ventricle in One Contraction

.

•

Heart Rate

Is

•

448

448 £$ Running Problem: Myocardial Infarction Overview of the Cardiovascular System .... 449 The Cardiovascular System Transports Material Throughout the Body 449 The Cardiovascular System Consists of the Heart and Blood Vessels 450 Pressure, Volume, Flow,

The

Pressure of Fluid in

and Resistance

....

478

Compressing

Its

488

O Running Problem: The Blood •

Blood Vessels Contain Vascular Smooth Muscle

Resistance Opposes Flow

454

•

Arteries

Depends on the Flow Rate and the Cross-Sectional Area

455

•

Exchange Between the Blood and

Anatomy Summary: The Heart Cardiac Muscle and the Heart The Heart Has Four Chambers

458

Blood Flow Converges in the Venules and Veins

493

459

Cardiac Muscle Cells Contract Without Nervous Stimulation

460

•

•

461

When It

(

Cardiac Muscle

More

ontracts

Is

.

.

.

462

•

463

•

464

466

Heart Rate

Fleet rk I

i


Mechanics of Breathing

519 521

Answers

522

•

Q$ Running Problem: Emphysema The Respiratory System Anatomy Summary: The Respiratory System he Bones and Muscles of the Thorax Surround the Lungs

546 546 547 ...

548

I

>

Blood

O •

523

Running Problem: Von Willebrand'S Disease

.

.

.

Plasma and the Cellular Elements of Blood • Plasma Is Composed of Water, Ions, Organic

524

JT' Clinical Focus: Cell Count •

Blood • •

('ell

•

Differential

White

Hematopoiesis

Is

Factors,

Bone Marrow

Colony-Stimulating Factors Regulate Eeukopoiesis

Thrombopoietin Regulates

•

Biotechnology: Blood

Red Blood •

.

.

allure

Cells

Mature Red Blood Cells Lack

a

Nucleus

Is

Is a

Mixture

551

a High-Flow,

552

552 552

ol Ciases

Move from

Areas of Higher Pressure

553

to Areas of lower Pressure

Law Describes Pressure-Volume 553

Ventilation 528

554

The Airways Warm, Humidify, and Filter Inspired Air

554

During Ventilation, Air Flows Because 554

of Pressure Gradients

When

Inspiration Occurs

Alveolar

Pressure Decreases

529 (

Air

Relationships of Gases

Platelet

ell

Gas Exchange

he Pulmonary Circulation ow-Pressure System

Boyle's

529




t

tis-

•Ralph W. Gerard, Mlnoi to Physiology: Self Survey of Physiological Science (Washington, D.< \merlcan Physiology Society, 1958) \

Outside

coming from the sensor

sues controlled by Integrating centers are

.:

Within desired rar ige

an integrating center

integrating center

response thai

1-60).

desirable range, specialized

a signal to

variable back Into the desired range,

K

or motors.

filters,

the maintenance of a relatively stable internal environment.

stasis,

The body has

lated

pumps,

the body

activ ated

sends signal

X

to [

|4ntegrating

center

Physiological control n items keep regulated variables within n desired range timing homeostasis

Figure 1-6

Themes

Cotnpartmentation of the body and of branes separate

within a

fluid. Similarly,

membranes

cell,

Input

divide the cell into dis-

compartmentation, or the

crete units or organelles. This

Physiology

mem-

cells Cell

from each other and from the extracellular

cells

in

pres-

ence of separate compartments within the body, allows different To maintain constant level, output must equal input.

areas to specialize their functions.

Communication cells of

that the

and

Most

efficiently.

and homeostasis both require

Integration

the body communicate with one another rapidly

communication uses chemical

cell-to-cell

with the nervous system adding speed by sending

signals,

may

Information

cal signals.

pass from

one

communication) or from one part of the body

(local

(long distance communication).

Movement

latory system aids long distance chemical

Communication between the cells

and the

across the

enter the

the

cell to its

of blood in the circu-

internal

Output

environment of the

requires information transfer

extracellular fluid

message must be trans-

In these instances, the

membrane and translated into an intracelluprocess known as signal transduction. Chemical

ferred across the cell lar signal,

a

communication and detail in

Chapter

•

Mass balance

Figure 1-7

in the

body

are able to

but others are unable to cross the barrier created by

cell

membrane.

cell

to another

communication.

membrane. Some chemical messengers

cell

electri-

neighbors

signal transduction are discussed in

behavioral responses bring the body back into balance. The law of

mass balance Total

summarized by the following equation:

is

amount

(or load) of

substance x in the body

= intake + production - output

more

Substances whose concentrations are maintained through mass

6.

balance include oxygen and carbon dioxide, water,

Movement Movement

of Substances across

of water, gases, and other molecules between the

and

intracellular

extracellular

the barrier of the

evolved that allow terials

logical

Membranes

compartments requires crossing

membrane.

cell

they allow in or out. The details of

membranes

movement

be discussed in Chapter

will

to

input of energy. stored? As

the body

across bio-

this

energy

come

continuous

from, and

those questions, you will learn

range.

Mass Flow

Mass balance

We

function of time.

talk

in the

body

usually discussed as a

is

about sodium intake per day or carbon

how

how

flow,

is

an important consideration. This

is it

Mass Balance

membranes, and

to create

Another important concept

the law of mass balance. This law says that

substance in the body

(amount

(amount min)

vol)

by an equal

For example, a person

movement.

is

to

loss (Fig,

if

in

the

physiolog\

amount

remain constant, any gain must be

is

of a off-

given

is

given an intravenous infusion of glu-

at a rate of

liter.

(in

from the body are the urinary and digestive

the urine and

integumentary system internal

and external

mass balance.

When

is

50 g glucose 1000 ml. solution x 2

mL

solution

= In

physiology

we

min

0.1 g glucose

are also concerned with the

min

movement

of

substances within and between compartments of the body.

Most substances enter the body from the outside environment, although some, like heat, can be produced internally. The for loss

the infusion

2 milliliters per minute, the mass flow for glu-

l-7«). For example, to maintain con-

environment.

major routes

If

cose would be

body temperature, heal gain from the external environment and from metabolism must be offset by heat loss back to the ex-

systems

mini

(vol

stant

.

expressed as mass

concentration x volume flow

Mass flow

energy in

cose containing 50 grams ot glucose per

ternal

is

where

used for synthesis and breakdown of molecules, to trans-

port molecules across cell

set

and hy-

dioxide output per minute. Thus, the rate of intake, production, or

5.

.iving processes require the

Where does

we answer

is

I

salts,

our bodies have regulatory mechanisms

keep temperature and energy stores within an acceptable

output

Biological Energy

ions. In addition,

Specialized processes have

be somewhat selective about what ma-

cells to

drogen

feces),

(skin).

the respiratory system, and the

Sensors that detect changes in the

environments monitor some

mass balance

is

aspects of

disturbed, physiological

and

Blood flows in the circulatory system; the lungs; gases, nutrients, and wastes In each instance,

movement

air

flows into and out of

move

into

and out of

or flow of the substance

is

cells.

created by

a driving force such as a pressure or concentration difference (a

gradient). In

many

flow,

and

is opposed by friction or The concepts of gradients.

situations, flow

forces that create resistance to flow.

resistance will be reintroduced in Chapter

5.

8

1

CHAPTER

INTRODUCTION TO PHYSIOLOGY

1

The seven themes

appear over and over

just described will

again in the subsequent chapters of the book. Look for

the

summary

end of the chapters and

material at the

them

in

in the end-

of-chapter questions.

vestigator in the bird experiment

changed to

food intake increased, she could not determine

if

the increased

food intake was due to temperature or to more palatable food unless

she had a control group that was also fed the different food.

During an experiment, the investigator carefully

CHECK

Answers:

p.

collects in-

formation, or data Iplural; singular datum, a thing given], about

1

on the

the effect that the manipulated (independent) variable has 1

.

a

If

person eats

milligrams of

remaining

it

1

2 milligrams of

in

day and excretes

salt in a

1

observed (dependent) variable. Once the investigator

the urine, what happened to the

analyze the data. Analysis can take

many

cludes statistical analysis to determine statistically significant.

THE SCIENCE OF PHYSIOLOGY How

ments of

Observation and experimentation are the key

hypothesis

using

and,

The next

designing an experiment

knowledge,

aspect of the

step

generates

about

a

how by

to test the hypothesis

is

which the

in

ele-

investigator observes an event prior

[hypotithenai, to assume], or logical guess,

the event takes place.

some

An

scientific inquiry.

phenomenon

or

graph

do we know what we know about the physiology of the

human body?

feels that

she has sufficient information to draw a conclusion, she begins to

milligram?

1

and

a different food,

If

apparent differences are

A common format

1-8*, Focus on Graphs,

in-

for presenting data

is

p. 12).

one experiment supports the hypothesis that cold causes

sure that the results were not step

is

called replication.

an unusual one-time event. This

When

data support a hypothesis in

may become

multiple experiments, the hypothesis

a scientific

theory.

Most information presented

one

in textbooks like this

On

new

occasion,

ex-

Good Scientific Experiments Must Be

perimental evidence that does not support a current model

Carefully Designed

published. In that case, the model must be revised to

element, or variable, that the investigator thinks

phenomenon. That

independent variable. For example, at a feeder

seem to

She generates

some

of biological experiment removes or alters

part of the observed

eat

more

is

an essential is

which she

will

keep birds

than

in the

which

is

summer.

her experiment, tem-

hypothesized to be dependent on tempera-

becomes the dependent variable.

example,

For

membrane was

Answers:

the laboratory execute an experiment

in

p.

1

urine output

in

the hour following drinking.

independent and dependent variables

which globules of proteins

essential feature

spect except thai the

l

result,

the

that

cell

is

manipulated variable

normal value. For example,

a

In

a sel

is

What

ol

birds

are the

cold temperatures,

rhe purpose

hanges are due

changes

In

some

oi

re-

not changed from

like

the control

to the

at

warm

the birds held is

.it

to ensure thai

experimental manipulation

other variable

1

01

example,

11

in

cell

membranes, and students who had learned the butter sandwich

model had

to revise their

mental model of the membrane.

human physiolog) come from? We have learned much of what we know from experiments on animals ranging from squid to rats, in many instances, the scientific

models

for

nonhuman models

enough

humans.

that

we

is

impor-

because experiments using

human

to

It

subjects can be difticult to perform.

control. A control

maintained

model of the membrane, one

within a double layer of

can extrapolate from the animal model

the bird-feeding experiment,

temperatures but otherwise treated exact!)

c

sci-

textbook writers had to revise their descriptions of

float

the experiment?

in

any experiment

the control group would be

10

learned

As a

tant to use

usually a duplicate of the experimental group in ever)

to

in the inter-

fats.

hum. ins.

and not

students

entists presented a very different

However, not

an) observed

in-

sandwich," composed of two layers of

physiological processes are identical or similar

which

they drink different volumes of water and measure their

its

1970

in

a "butter

Where do our

CHECK in

temperatures

the independent variable.

ture,

is

at different

eat. In

intake,

is

have discovered

be

the val.

Food

An

scientists

may

proteins with a layer of fats sandwiched between. But in 1972

perature, the manipulated element,

group

learn a physiological

"fact" while using this textbook, in 10 years that fact

what

the avail-

hypothesis that cold temperatures cause birds to

a

in

Students

fit

is

a biologist notices that birds

in the winter

and monitor how much food they

2.

you may

able evidence. Thus, although

accurate because of

element

altered

increase their food intake. To test her hypothesis, she designs an

experiment

is

based on theoretical models that scientists have developed from the best available experimental evidence.

A common type

a

birds to eat more, then the experiment should be repeated to en-

investigator manipulates

phenomenon.

(see Fig.

if

forms and usually

the in-

l)

I

all

studies

done on animals can be applied

by Europeans

for years

was undergoing stringeni testing

quired b) the U.5. food and Drug Administration before be sold in this country. a

to

or example, an antidepressant that had been used safe-

When

it

re-

could

beagle dogs were given the drug for

period ol months, the dogs started dying from heart problems.

S< leiitists

were alarmed

until luithei research

showed

that beagles

unique genetic makeup thai causes them to break down the drug Into more toxic substance. he drug was perfot tl) satewas subsequent!) in other kinds ol dogs ,\t)i.\ In humans and have

a

.1

I

it

approved

fbl

human

use

The Science

The Results of Human Experiments Can Be Difficult to Interpret There are

many

periments

and

reasons

it is

difficult to carry

humans, including

in

up an experiment with human subjects, we must control the placebo effect. The simplest way to do this is

In setting

try to

out physiological ex-

variability, psychological factors,

ethical considerations.

with a blind study,

which the subject does not know whether

in

he or she

is

receiving the drug or the placebo. Even this can

however,

if

the researcher

who

Human

and environmental

populations have tremendous genetic

variability.

Although physiology books usufunctions such as blood

ally present average values for various

number

pressure, these average values simply represent a

somewhere near the middle

falls

to

show

significant differences

human

groups in a

that

of a wide range of values. Thus,

between experimental and control

experiment, an investigator would,

ideally,

have to include large numbers of identical subjects.

who

However, getting two groups of people every respect

recruit subjects

may have

who

The

researcher then

are similar in as

must attempt

to

seen advertisements in newspapers requesting volun-

body weight,

of ideal

ability inherent in

even

to participate in a study ..." The vari.

a select

measurements or

their

interpretations.

To avoid

not involved in the experiment,

which group group

is

is

who knows and which

receiving the experimental treatment

is

The most sophisticated

experimental design for minimizing psychological effects

the

is

which the control group

in the

experiment becomes the experimental group in

half of the

first

in

re-

a third party,

the only one

receiving the control treatment.

color

outcome,

this

which

searchers often use double-blind studies, in

may

the second half, and vice versa.

many aspects as possible. You

"Healthy males between 18 and 25, nonsmokers, within

teers:

10%

impossible.

is

researchers'

expectations of what the treatment will or will not do

double-blind crossover study,

are identical in

The

receiving.

is

fail,

knows

assessing the subject

is

which type of treatment the subject Variability

of Physiology

group of humans must be taken

when doing experiments with human subjects, bevariability may affect the researcher's ability to accurately

Ethical Considerations

mans

Ethical questions arise

are used as experimental subjects, particularly

when when

subjects are people suffering from a disease or other illness. ethical to

withhold

a

new and promising treatment from

group? A noteworthy example occurred

huthe Is it

the con-

few years ago

when

into account

trol

cause

researchers were testing the efficacy of a treatment for dissolving

on

interpret the significance of data collected

One way to human

reduce

whether

or animal,

to

is

do

a

blood clots in heart attack victims. The survival rate

that group.

within a

variability

test

population,

crossover study. In a

control. Thus, the individual's response to the treatment can

be compared with

the

when

method

is

within

population. For example, in a

a

particularly effective

ication, subjects

own

individual's

control

there

is

value.

wide

blood pressure med-

test of

an inactive substance (placebo, from the Latin first

perimental drug, then changes

half,

(iroup B starts with the ex-

effecl

oi

scheme

the drug

al-

on each

individual. Statistically, the resulting data can be analyzed using

methods

different

that look at the

changes

in

each Individual

rather than at changes in the collective group data.

Placebo and Nocebo Effects Another in human studies is the psychological aspect treatment. will

you give someone

help them, there

effect,

This

If

even

is

a

if

the

is

pill

a

a pill

and

tell

significant variable

administering

ol

the person that

strong possibility that

it

will

a

if

you

have specific adverse side

people that effects,

a

have that

drug they are taking

those people will report

er incidence of the side effects than a similar

were not warned. This phenomenon from the Latin word

nocere, to

may

high-

who

nocebo effect, do harm. The placebo and nocebo is

effects show the ability of our minds to

functioning of our bodies.

a

group of people

on some anticancer agents have shown

the experimental treatments were

less effective in

that

stopping the

spread of cancer than were the standard treatments used by the controls.

Was

it

ethical to undertreat the experimental patients

by

depriving them of the more-effective current medical practice?

Most studies now are evaluated

as rhey progress to

possibility that participants will be

A

recent

women

that

trial

harmed by

taking a

halted early

pill

when

women on

placebo

in

post-

investigators realized

with two different hormones were de-

veloping cardiovascular disease and breast cancer

than

minimize the

their participation.

on hormone replacement therapy

women was

menopausal

pills.

On

at a

the other hand, the

ceh Ing hormones also had

a lower rate of

fractures, the investigators

decided that the

higher rate

women

re-

colon cancer and bone risks associated

with

hormones exceeded the potential benefits, and the study was stopped. To learn more about this clinical trial and the taking the

pros

contains only sugar or an inert substance,

tell

In contrast, tests

and

cons

of

hormone

replacement

therapy,

go

to

it

well-documented phenomenon called the placebo

effect. Similarly,

the

that control groups could also be given the experimental drug.

changes to the

to the placebo. This

lows the researcher to assess the

A takes

for "I shall be

half of the experiment, then

experimental drug for the second

his

variability

might be divided into two groups. Group

pleasing") for the

I

among

was so much higher that testing was halted so

treated patients

crossover study, each subject acts both as experimental animal

and

a

called a

alter the physiological

wwwMlmMih.govfynedlineplusAiormonereplacementtherapy.html, the website of the U.S. National

1

Unary of Medicine.

Human Studies Can Be Designed in

Many Formats

Almost daily the newspapers carry Studying the efficacy are

many

ol

articles

about clinical

trials

drugs or other medical treatments. There

different aspects of experimental design that can affect

the validity

and

ample, some

applicability of the results of these

trials are carried

trials.

For ex-

out for only a limited period of time 11

8

CHAPTER

INTRODUCTION TO PHYSIOLOGY

1

FOCUS ON Figure 1-8

»

Graphs Graphs are

two

more) different

(or

(Fig.

between

pictorial representations of the relationship

l-8a#).

variables, plotted in a rectangular region

We use graphs to

present a large

amount

KEY Key

of numeri-

y-axis

emphasize comparisons between

cal data in a small space,

The standard features of a graph include units and labels on the axes, a key, and a figure legend. (a)

vari"1

show trends over time. A viewer can extract information much more rapidly from a graph than from a table of numbers or

1

ables, or

from

A

a written description.

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know about the data, including the purpose of the experiment, how the experiment was conducted, and the results. All scientific

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3 ai

Elements and Atoms

commonly

en-

countered in biological systems. Those that are necessary for

life

Only about one-fourth of the elements

major

are called essential elements. Eleven are

found

human body

in the

hydrogen

common

oxygen

(H),

in fairly large

and nitrogen

(O),

are

essential elements

amounts. Carbon

by

(N) are

far

The major

make up most elements are shown

essential

Put the correct answers particles in the left

tial

elements (blue squares in the periodic table in

the er

list

has atomic mass of

3.

neutron

(b)

found

4.

proton

(c)

negatively charged

(d)

changing the number of these in an atom creates a new element

1

biologiin

pink

Fig. 2-2). All of

in

the nucleus

Use the periodic table of the elements

Figure 2-2 to an-

in

swer the following questions: 5.

Which element has 30 protons?

of such elements continues to change as scientists discov-

6.

How many

electrons does

one atom

of

7.

How many

electrons does

one atom

of calcium (Ca) have?

8.

What

9.

What element

more about how minor

tain

amu

(a)

and

the trace elements are essential in

to cell function,

Many modern

work.

cells

some way

vitamin

pills

con-

sodium (Na) have?

elements such as selenium, chromium,

essential

manganese, and molybdenum.

The need

48

than once.

2. electron

minor essen-

tions in living tissues are called trace elements, or

may be used more

(C),

elements that are found in very low concentra-

essential

p.

the right column with the subatomic

in

column. Answers

squares in the periodic table in Figure 2-2.

The

Answers:

the most

essential elements because they

cal molecules.

CONCEPT CHECK

for trace

elements

evident only

is

when they

are

the average atomic mass of nitrogen?

is

illustrated

is

by the atom

in

Figure 2-1 ?

absent from a person's diet or present in insufficient quantities. For example, a lack of iodine in the diet causes low thyroid hor-

mone

production, which

and symptoms such

physical signs

One

tolerate cold.

trace

tion in recent years

and

element that has received a

chromium

ican public as

as fatigue

chromium, usually marketed

is

A

picolinate.

inability to

What

lot of atten-

element that

to the

deficiency of

body has been postulated (but not proven)

in the

RUNNING PROBLEM

then reflected by development of

is

Amer-

diet,

some

The atoms protons in

its

fact that

um

The next element,

um

two protons, followed by lithium

in its nucleus.

protons,

and so on. The number

ement

called the

table

is

In

the

brewer's yeast, broccoli, mush-

chromium

chlo-

poorly absorbed from the digestive

tract,

food and

in

chromium uptake

at the intestine.

lowance (RDA)

chromium

is

in

compound chromi-

from amino

picolinate. Picolinate, derived

of

an essential

is

acids,

enhances

The recommended

daily al-

50 micrograms. As we've seen,

Stan takes several times this amount.

nucleus. For example, the lightest element, hydro-

one proton

is

from one

each element has a unique number of

gen, has only (He), has

in

Chromium

is

(Cr)

normal glucose metabolism.

so a scientist developed and patented the

people.

another by the

found

is

supplements

ride

to be associat-

of different elements are distinguished

linked to

is

chromium

Chromium

picolinate?

rooms, and apples.

chromium

ed with the metabolic disease diabetes mellitus ("sugar diabetes") in

chromium

is

of protons in

atomic number

1.

The

at

ments.

with three

one atom of an

of the element.

arranged by atomic number, starting

atomic number of

(Li)

Question

heli-

Locate chromium on the periodic table of the

1:

What

chromium's atomic number? Atomic mass?

is

How many electrons

does one atom of chromium have? Which

el-

elements close to chromium are also essential elements?

The periodic

oQooooo

hydrogen, with an

end point of the periodic table

is

ele-

con-

stantly shifting as scientists find evidence for additional very short-lived elements (see Explorations at the for the story of a scandal associated

end of the chapter

with this research).

The average atomic mass of an element is shown below the symbol of the element. Atomic mass is calculated by adding the mass of the protons and neutrons in one atom of the element. For example, one atom of carbon has

six

protons and

Because the mass of each proton or neutron unit, carbon's table,

box

not

all

atomic mass

12 amu. However, in the periodic

is

with is

1

7

protons in

periodic table

is

a

known

nucleus,

shows an

20.

The atomic mass

in the

weighted average of the different forms of the

element. In the next section are

its

The number of protons stant

the (Fig.

we

as isotopes.

will discuss these different forms,

in

and distinguishes

number

Atoms

2-3 •).

for

the upper

is,

as isotopes of the

is

con-

others. However,

element

is

variable

numbers of same +

[/so-,

the same place in the periodic table)]. The

of the chemical letter symbol.

left

For example, *H, hydrogen-1,

(Fig.

all

an isotope shows the atomic mass number written to

occurring isotope of hydrogen, us

from

of an element that have different

known

tupos, place (that

symbol

one atom of any given element

that element

of neutrons in the atoms of an element

neutrons are

because chlorine comes in two forms,

one with 18 neutrons and one with

which

six neutrons.

one atomic mass

atomic masses are whole numbers. For example, the

for chlorine (CI),

atomic mass of 35.5. This •

is

Isotopes of an Element Are Atoms with Different Numbers of Neutrons

2-4 •).

or deuterium

Hydrogen 2

(

H),

lc

also has

is

the most

common

has a single proton in

two other

and hydrogen-3, or

naturally its

nucle-

isotopes, hydrogen-2,

tritium

f

(

formed by the addition of one or two neutrons

H),

which

are

to the nucleus

23

CHAPTER

2

ATOMS, IONS, AND MOLECULES Adding one neutron to hydrogen's one proton

(Fig. 2-4b,c).

ATOMS

an atomic mass of 2

sults in

atomic mass of 3

3 (

2 (

two neutrons

H); adding

same chemical properties because these properties

number

consist of \

)

g% W

which

Neutrons

Protons

Elect rons

are

called

is

radiation. Every element has at least one radioisotope, most of

w

\

of neutrons.

and the energy they emit

radioisotopes,

by

are affected

and emit energy. These unstable isotopes

are unstable

called

have the

and medicine, because

Isotopes are important in biology

some

an

yields

H). All isotopes of a single element

the electron configuration and not by the

re-

produced

are

by using high-energy

artificially

particle ac-

A

celerators to "shoot" extra neutrons into a stable nucleus.

number

of elements, such as carbon

small

and uranium, have naturally

occurring radioisotopes. An

ate

m

An

that

ato m that

An atom

that

gains or loses

gains or loses

gains or loses

electrons

protons becor nes a

becomes an

becor nesan

neutrons

Both

artificial

and natural radioisotopes have medical

example, radioisotopes such as thallium-201

body

ages of the inside of the

201 (

uses. For

produce im-

T1)

for diagnostic procedures (those that

identify disease). Radioisotopes are also used to treat cancer, Ion of the

Different

Isotope of the

same element

element

same element

A map showing

Figure 2-3

elements, ions, isotopes,

the relationship between

and atoms

ample of

The use of radioisotopes

therapeutic use.

m

and treatment

of disease

is

a specialty

known

an ex-

in the diagnosis

as nuclear medicine.

mmuiiHs

Radioisotopes and Nuclear Medicine

Of the 2000 known isotopes

of the elements, unstable iso-

topes that emit radiation outnumber the stable isotopes

Some

four to one.

A

artificially,

including

naturally, all

but

those with

atomic numbers of 84 or higher. Radioisotopes emit three

hydrogen atom has one proton in the nucleus and one orbiting electron, but no neutrons.

t.

occur

of these isotopes

many have been made typical

gamma

types of radiation: alpha («), beta (p), and

(7).

Alpha and beta radiation are composed of fast-moving

(a)

Hydrogen-1, H

particles (protons

+

an unstable atom.

Gamma

radiation

energy waves rather than

particles.

neutrons, or electrons) ejected from

particles. X-rays are similar to

A

«o

Radioisotopes are widely used sis

and treatment.

used by (b)

127

Hydrogen-2, deuterium,

2

l,

useful for diagnosis

is

disorders. it

does

13,

little

damage, but

Two

radiation

13, l,

in

medicine

for

diagno-

of thyroid gland

radiation. In small doses

larger doses can

be administered

when

the gland

overactive. Another widely used radioisotope for diagnos-

to the nucleus, creating 3 H.

tic

procedures

bound

is

technetium-99, an element that can be

to carrier molecules that target

it

to specific tissues.

CHECK

Hydrogen-3, 10.

24

Figure 2-4

'

is

neutrons have been added

Anvwi

1

tritium.

•

is

a radioactive isotope of

and treatment (3

is

and are

instances, the radioisotope

emits both a and

l

radiation

interior.

to selectively destroy thyroid tissue

J, (c)

some

For example,

itself.

H

"

In

of high-

deeply than a or p

gamma

used to create images of the body's

neutron has been added to the nucleus,

creating the isotope 2 H.

Gamma

much more

able to penetrate matter

-

composed

is

Isotopt

hydrogen

What

are the atomic masses

isotopes

shown

in

(in

Figure 2-4?

amu)

of the three

hydrogen

1

.

Elements and Atoms

Electrons

Form Bonds Between Atoms

(a)

and Capture Energy Electrons, the third

subatomic

particle, play a significant role in

The arrangement of electrons around the nucleus

physiology.

de-

termines the ability of an atom to bind with other atoms and

form molecules. The gain or cal

loss of electrons

changes the

electri-

charge on an atom and plays an essential role in communica-

on

tion throughout the body. Finally, electrons

processes.

life

The

electrons in an

atom do not move around the nucleus

random. Instead, they are arranged

The lowest energy

shells.

to other

it

movement and

molecules, so that the energy can be used for

other

atoms can

certain

capture energy from their environment and transfer

level,

energy

in a series of

designated as level

1, is

at

levels, or

Nucleus closest to

the nucleus. As distance from the nucleus increases, energy levels increase.

Each energy

torical reasons,

s,

p,

level

|

Appendix A

1

brackets around the symbol for a solute are the shorthand nota-

Another way to write This equation states that

pH

]

and

between

pH

of a solution

pH

is

1

cause [H

pH

H

+

less

+ is

]

is

measured on

numeric

a

Chemical

--

Household ammonia

--

is

meaning

Soap

H

its

pH

scale

7.

H+

Baking soda

concentrations. Be-

Pancreatic secretions

Solutions that have lost

H+

to a base

have

Compatible with human

a lower

concentration than pure water; they are called alkaline. They

have

pH

a

value greater than

7.

Remember, because pH +

tional to the reciprocal of the [H tration increases, the

The pH value of

scale

pH number

],

as the

is

Saliva

hydrogen ion concenUrine (4.5-7)

meaning

change

that a

pH

in

unit indicates a 10-fold increase or decrease in the hy-

1

drogen ion concentration. For example,

if

the

pH

of a solution

4-

ible

from

with

a

pH

of 8 to a

life.

Vinegar, cola

Lemon

1

•

Buffers are a key factor in the body's ability to maintain nor-

mal pH. A buffer

is

any molecule that moderates changes

Many

buffers are anions that

cules.

When

buffers

f

free

bond

Fi

is

to the

H

have a strong

added to +

a solution

affinity for

a buffer

used

pH of swimming pools and spas. The following shows how sodium bicarbonate buffers a solution to

When

which hydrochloric acid (HC1) has been added.

HO dissociates into FT

solution,

If

and CI

some

is

of the

present,

H

to

some

of

form undis-

carbonic acid. The removal of free FT lowers the

+ CI

+

I

ICO.

'

40.

When

the

body becomes more

acidic,

does the pH increase

or decrease?

41

How

.

can urine, stomach acid, and

outside the

pH range

part of the living

that

is

saliva

have pH values

compatible with

1

1

con-

k BIOMOLECULES Most of the molecules three elements in

concern

ol

common: carbon

in

human

(C),

=^H

2

CO,

+ CI

molecules, because

+ Na'

Hydrochloric

Sodium

Carbonic

Sodium chloride

100 amino acids)

have

l_ 1

"

2'-

structure

3° structure

structure

4° structure

1

Sequence of amino acids

1

Globular proteins

Fibrous proteins

P-pleated sheet

a-helix

•::•:

Multiple subunits

I

\

•

v.

;

"V

*

Figure 2-16

Map

of levels of organization in protein molecules

held in place by hydrogen bonds. In other proteins, sulfur atoms in

two

different cysteine molecules

in a disulfide (S

—

S)

bond covalently

to each other

acids each.

The hemoglobin molecule

proteins based on their shape. Globular proteins have

amino

acid chains folded into ball-like shapes. Fibrous proteins are

found as pleated sheets or in long chains that

wind around

carrying pigment found in red blood

The

ble in water, are important structural tissues.

Examples include

a

fibrous proteins,

number which

collagen, a fibrous protein

found

and

nails.

The globular proteins

making them

soluble.

cells,

has a quaternary struc-

of 146

in

and

many

They may

They act them and

are soluble in water.

said to

two polypeptide alpha chains of

cells

types of connective tissue, and keratin, a fibrous protein found in

Hemoglobin, the oxygen-

is

of impor-

are insolu-

components of

insoluble lipids in the blood, binding to

composed 141 amino acids each and two polypeptide beta chains of four subunits:

illustrated in

as carriers for

A protein with more than one polypeptide chain (Fig. 2-16).

and amino acids serve

tant functions in the body.

hair

each other.

is

Figure 2-16 under the label "Multiple subunits." Proteins, peptides,

Proteins are often classified as either globular or fibrous

ture

amino

bond.

have quaternary structure

•

also serve as enzymes that increase

the rate of chemical reactions. Soluble proteins also act as cell-tocell

messengers in the form of hormones and neurotransmitters

and

as defense

molecules to help fight foreign invaders.

39

CHAPTER

ATOMS, IONS, AND MOLECULES

2

CHECK

Answers:

p.

another kind of biomolecule. Proteins combine with

49

form lipoproteins. Lipoproteins are found mostly in

What

44.

the chemical formula of an

is

amino group? Of

a

carboxyl group?

Why must we

45.

They

branes.

also carry

terol in the blood: the lipid section of the

include essential

amino

acids

in

our diet but

lipoprotein-cholesterol

What aspect of protein structure allows proteins more versatility than lipids or carbohydrates?

to have

complex soluble

combine

Proteins

with

is

mem-

as choles-

makes the

entire

in water.

carbohydrates

glycoproteins. A "glyco-" molecule

cell

molecule interacts with

insoluble cholesterol while the protein section

not the other amino acids? 46.

hydrophobic molecules such

lipids to

composed

to

form

of a carbohy-

bonded to either a protein or a lipid (glycolipid). Glycoproteins and glycolipids, like lipoproteins, are important components of cell membranes (Chapter 5). The carbohydrate drate

Some Molecules Combine Carbohydrates, Proteins, Not

all

lipid.

•

and Lipids

biomolecules are pure protein, pure carbohydrate, or pure

Conjugated proteins

Map

Figure 2-17

are protein molecules

portions of these molecules are usually found on the external

combined with

of nucleotide

surface of the

NUCLEOTIDE

structure

cell,

where they can form hydrogen bonds with

NH 2

N^

^

C

CH

II

1

HC^ ^C x / N N II

II

II

O^

-o-p- -0-P-0-POCH 2 o-

o-

\

-o

/

ATP

OH consists of

Purine

H

N

^

HOCH 2

/

HC^

(A)

II

I

0'

N

Guanine

(G)

Cytosine (C)

Thymine

OH

HO

(T)

HO

Uracil (U)

Bases Adenine Adenine Adenine Adenine

+

ADP CAMP NAD

= = = =

DNA RNA

= A.G.C.T - A.G.C.U

+ +

ATP

O

"0-P-OH

OH

NUCLEOTIDES

+ + +

Sugar

Phosphate groups

Ribose Ribose Ribose

+

3

+ + +

2

2 Ribose

Deoxyribose

Ribose

+ +

Other component

— — —

1

+

2

NUCLEIC ACIDS:

40

OH

O

1

I

Adenine

OH

O

II

I

N H

HOCH 2

Deoxyribose

N^ ^CH

CH

II

HC Nx

Ribose

Pyrimidine

H

I

Phosphates

Sugar

Base

1 1

per nucleotide per nucleotide

Nicotinamide

—

Biomolecules

water and other molecules in body

Glycolipids are be-

fluids.

lieved to contribute to the stability of the cell

and glycolipids

glycoproteins

tain

receptors

and

act

as

O

membrane. Cer-

Nucleotide chains

membrane

cell

£3

markers. Membrane receptors bind to mole-

cell

cules outside the

The

cell.

markers identify

cell

label, so that

the defense cells of the body can

ence between

"self"

cells,

like a

U

the differ-

tell

and foreign invaders.

Nucleotides Transmit

Bases

and Store Energy

and Information Nucleotides play an important role in cell,

including the storage and transmission of genetic informa-

tion

and the

molecule composed of five-carbon sugar,

base

(Fig. 2-1

and

(1)

(3) a

single nucleotide

is

one or more phosphate groups,

\tle-,

without;

bases: the purines

-oxy-,

two

There are

Thymine _ Guanine

(2) a

C

Cytosine

U

Uracil

oxygen]. There

and the pyrimidines. The

purines have a double ring structure; the pyrimidines have a gle ring.

are subjected to increased energy

may meet

the

demand

for

demands over

cells,

a period of

more ATP by increasing the num-

ber of mitochondria in their cytoplasm.

59

r

_

CHAPTER

3

CELLS

AND

TISSUES

^l^m\ Inner

membrane Outer membrane

Cytoplasm

Cristae

Matrix

is

the

compartment

•

Figure 3-9

of

membrane

Mitochondria

Mitochondria have

The Endoplasmic Reticulum Is the and Lipid Synthesis The endoplasmic a

Matrix

The intermembrane space forms a compartment.

Cytosolic side

innermost

a

double wall structure with

Site of Protein reticulum, or ER,

network of interconnected membrane tubes

(Figs.

3-6

is

and

as

smooth membrane

reticulum

comes from the Latin word

for net

and

refers

to the netlike appearance of the tubules. Electron micrographs reveal that there are

two forms of endoplasmic reticulum: rough

tubes. Both types of

The smooth endoplasmic reticulum pholipids for the terol

is

cell

membrane

liver

Smooth endoplasmic reticulum

rough appear-

cytoplasmic surface.

lacks the ribosomes

and appears

storage,

and kidney

muscle

cells, a

is

are

the main

[©

site for

p. 35].

produced here, and choles-

The smooth endoplasmic reticulum of

cells detoxifies or inactivates drugs. In skeletal

2+ )

to be used in muscle contraction.

are attached

to cytosolic side of

rough endoplasmic reticulum.

y% •

Smooth endoplasmic reticulum lacks ribosomes.

The hollow tubes

ER

60

The endoplasmlt reticulum

of the

are formed by a continuation

of the outer nuclear

Figure 3-10

Phos-

modified form of smooth endoplasmic reticulum

stores calcium ions (Ca

Ribosomes

•

and

modified into steroid hormones, such as the sex hormones

Rough endoplasmic reticulum has

its

(SER)

the synthesis of fatty acids, steroids, and lipids

estrogen and testosterone.

a granular or

endoplasmic reticulum

transport of biomolecules.

endoplasmic reticulum and smooth endoplasmic reticulum. ance from rows of ribosomes dotting

inner membrane.

have the same three major functions: synthesis,

3-10 •) that are a continuation of the outer nuclear membrane.

The name

a heavily folded

membrane.

•

Cellular

The rough endoplasmic reticulum (RhR)

is

the

main

at-

tached to the cytoplasmic surface of the rough endoplasmic

exported to other parts of the body. (Secretion

The Golgi Apparatus Packages Proteins into Membrane-Bound Vesicles The Golgi apparatus dig. 3-1 19) described by Camillo Golgi in 1898. For years,

vestigators thought that this organelle

was

some

just a result of

the

microscope. However,

we now know from

scope studies that the Golgi apparatus

nous organelle.

Its

function

is

to

is

fix-

electron micro-

indeed another membra-

modify proteins made by the

rough endoplasmic reticulum and package them into membranevesicles.

The Golgi apparatus consists of five or six hollow curved sacs stacked on top of each other like a series of hot water bottles and connected so that they share a single lumen. The convex side of the stack faces the

rough endoplasmic reticulum and

ceives the transport vesicles from

it.

which

re-

These transport vesicles fuse

with the membranes of the Golgi sac and discharge their con-

is

the process by

substance into the extracellular space.) The

contents of most storage vesicles, however, never leave the cytoplasm. Lysosomes are the major storage vesicles of the

cell.

Lysosomes Are the Intracellular Digestive System Lysosomes

[lysis,

dissolution + soma, body] are small, spherical

storage vesicles that appear as

cytoplasm

and

(Fig.

membrane-bound granules

in the

3-120). Lysosomes contain powerful enzymes

They take up bacteria or old organelles, such as mitochondria, and use the enzymes to break them down into their component molecules. Those act as the digestive

system of the

cell.

molecules that can be reused are reabsorbed into the cytosol, while the of

rest are

dumped

enzymes have been

out of the

identified

cell.

As

many

as

50 types

from lysosomes of different

cell types.

The

enzymes of lysosomes are not always kept isomembranes of the organelle. Occasionally, lysotheir enzymes to dissolve extracellular support

digestive

lated within the

somes

lumen.

a cell releases a

in-

ation process needed to prepare tissues for viewing under the

its

be attached to proteins to

storage vesicles. Secretory vesicles contain proteins that will be

tips of the

the Golgi apparatus.

tents into

be modified

be cleaved into

vesicles shuttle their contents across the cytosol to

pinch off from the

bound

may

may

Cytoplasmic vesicles are of two kinds: secretory vesicles and

membrane-bounded transport

der| that

light

smaller proteins or carbohydrates

may

vesicles [vesiada, blad-

spherical

first

the sac, they

endoplasmic reticulum.

where they undergo

chemical modification. Most of these proteins are packaged into

was

move through

by enzymes. For example, long proteins

make glycoproteins. Finally, the processed proteins are enclosed in membrane-bounded vesicles that pinch off from the concave face of the Golgi apparatus and move out into the cytosol.

reticulum, then inserted into the lumen,

The transport

As the proteins

site for

the synthesis of proteins. Proteins are assembled on ribosomes

Anatomy

release

Secretory vesicles leave filled with newly packaged proteins.

4

>**?

/» V Transport vesicles bring newly synthesized proteins from the endoplasmic reticulum to the

•

Figure 3-1

1

The Golgi apparatus

Golgi apparatus.

61

.

CHAPTER

CELLS

3

AND

TISSUES

One

of the best-known lysosomal storage diseases

known

herited condition

Sachs disease have defective lysosomes that glycolipids in nerve

symptoms

causes

cells.

is

the fatal in-

as Tay-Sachs disease. Infants

with Tay-

to break

fail

Accumulation of glycolipids

down

in the cells

nervous system dysfunction, including

of

blindness and loss of coordination. Most of the afflicted infants die in early childhood.

Lysosomes and peroxisomes are vesicles

filled

Peroxisomes Contain Enzymes That Neutralize

with enzymes.

Toxins

f;.y

:

\

Peroxisomes

1

-

tdur'l

some ,

***?,

now know

some, but we

Peroxii

1

.

.,/

kind of lyso-

a

that they contain a different set of en-

zymes. Their main function appears to be to degrade long-chain fatty acids

and potentially toxic foreign molecules.

name from

Peroxisomes get their inside

Lysospme

even smaller

are storage vesicles that are

than lysosomes. For years, they were thought to be

cule.

the fact that the reactions

them generate hydrogen peroxide (H 2

The peroxisomes

a toxic

2 ),

mole-

rapidly convert this peroxide to oxygen

and water using the enzyme

catalase.

Peroxisomal disorders

dis-

rupt the normal processing of lipids and can severely disrupt the

normal function of the nervous system by

altering the structure

membranes.

of nerve cell

CHECK 7.

•

Answers:

p.

83

What

is the anatomical difference between rough endoplasmic reticulum and smooth endoplasmic reticulum?

What

is

the functional difference?

Lysosomes and peroxisomes

Figure 3-12

How do

8.

material, such as the hard calcium carbonate portion of bone.

How

9.

lysosomes

release of lysosomal

enzymes has been impli-

from peroxisomes?

does the physiological theme of compartmentation

membranous

apply to

The inappropriate

differ

mitochondria

in

organelles

in

general and to

particular?

cated in certain disease states: for example, the inflammation and destruction of joint tissue in rheumatoid

10. Microscopic examination of a cell reveals arthritis.

mitochondria. In other instances, cells allow the

to

come

of

all

in

enzymes of

their lysosomes

or part of the

mass

is

this

many

observation imply about the

energy requirements?

contact with the cytoplasm, leading to self-digestion cell.

When

muscles atrophy (shrink) from lack

of use or the uterus diminishes in size after pregnancy, the loss of cell

cell's

What does

due to the action of lysosomes.

1 1

You are examining tissue from a previously unknown species of fish. You discover a tissue with large amounts of smooth endoplasmic reticulum in its cells. What is one possible function of these cells?

Because lysosomal enzymes are so powerful, one of the questions that puzzled researchers

mally destroy the

cell

was that these enzymes tions,

zymes

pH

is

first

If

will

it

The

pi

I

by very acid condi-

breaking

off

When

from the Golgi apparatus, their

in-

pH. Their inactivity serves as a form of

the lysosome breaks or accidentally releases the en-

not it

harm the

cell.

accumulates H

However, as the lysosome ions in

d

Once

down

this has oc( urred, the

sits in

conditions

known

Center

The nucleus

material thai

lysosomal storage diseases,

lysosomes are not effective because they lack

specific

enzymes,

processes.

How

the nucleus receives in-

in the cell or

elsewhere cell's

in

the body

protein synthe-

an active area of biological research, figure 3-13 • illustrates

sis is

the structure ol a typical nucleus, ["he boundary, or nuclear en-

velope,

a

is

(

j

is

membranes boles, oi

.is

all cell

and responds with line-tuned control of the

envelope

are capable ol

Cell's Control contains DNA, the genetic

formation about conditions

and the enzymes

enzymes

of the cell

ultimately controls

from the

various biomolecules.

in Inherited

The Nucleus Is the

process that uses ener-

inside the vesicle drops to 4.8-5.0,

are a< tivated.

62

they discovered

about the same as that of the cytosol, 7.0-7.3. The en-

the cytoplasm, gy.

are activated only

pinched

are inactive at this

insurance.

zyme,

What

100 times more acid than the normal cytoplasm.

lysosomes are terior

was why these enzymes do not nor-

that contains them.

i

two-membrane

structure that separates the nucleus

toplasmic compartment.

I

lie

outer

membrane

ol

the

connected with the endoplasmic reticulum, and both Ol

the envelope are pierced here ne

t

many

i

olumnai

polygonal

to

airways; female reproductive

Protein-secreting nils filled

I

witb membrane-bound secretory granules and extensive Rl R, Steroid se< reting cells contain lipid droplets

and extensive

open

em Ironmenl

Nose, trachea, and uppei

One side covered with cilia to move fluid across suifa< e

1 1

Sit irtory

the mouth, that

to the

SI

R

act

MX

line glands, in< hiding

p. liu reas,

swr.u glands,

salivar) glands,

endocrine

glands, sin

tin roid,

li

.is

gonads

68

.

'

Body

Tissues of the

Most

Cell organelles.

4.

Blood Capillary epithelium

merous

transport materials have nu-

cells that

mitochondria

provide

to

energy

processes (discussed further in Chapter

The

Pore

(a)

moved from

the extracellular

Leaky exchange epithelium allows movement through gaps between the cells.

5).

properties of transporting epithelia differ. For example,

glucose can be

Extracellular fluid

the lumen of the small intestine to

but cannot be

fluid,

um of the large intestine.

moved

Lumen

ous stimuli. Hormones, for example, of intestine or kidney •

Apical

membrane

by the epithelium of the kidney. You

•

Tight

—

more about

trans-

study the kidney and digestive

systems.

/wiAMTinMii Ciliated epithelia Ciliated epithelia are nontransporting

tis-

i

)

la

•J

parts of the female

lumen

tract.

covered with

cilia

that beat in a coordinated, rhythmic fashion,

moving

and

particles across the surface of the tissue. Injury

to the

surface of the tissue facing the

fluid

cilia

one

•

effect of

smoking.

It is

is

considered to contribute to the higher

incidence of respiratory infection in smokers, because the

Basolateral

is

movement.

or to their epithelial cells can stop ciliary

Paralysis of the ciliated epithelium lining the respiratory tract

•

•

•

The

reproductive

cell

•J[•

jj

and

sues found lining the respiratory system

epithelial

/

mucus

•

membrane

B

is no longer swept up out of the lungs by the 3-19# shows the ciliated columnar epithelium of the

that traps bacteria

Extracellular fluid _

cilia.

•

when you

porting epithelia

•

9

(Transporting

(b)

affect the transport of ions

will learn

•

•

junction

in response to vari-

• •

•

across the epitheli-

Furthermore, the transport properties of

an epithelium can be regulated and modified •

transport

for

a transporting epithelium prevent movement between the cells. To cross the epithelium, substances must go through two cell membranes. Tight junctions

Movement of substances

Figure 3-18

Figure

in

across tight

trachea.

and

leaky

Protective epithelia The protective epithelia are designed to prevent any exchange between the internal and external environ-

epithelia

ments. They are ers of cells.

environments. These epithelia are found lining the hollow tubes

and the kidney, where lumens open into

of the digestive system

the external environment [*

stratified tissues,

The epidermis

\epi,

composed x

upon

of

many

stacked lay-

derma, skin) and linings of

the mouth, pharynx, esophagus, urethra, and vagina are tective epithelia.

The multiple

cell layers

There are several characteristics of transporting epithelia

Some

of

these tissues are toughened further by the secretion of keratin [keras,

(Fig. 3- 18b):

pro-

of this tissue type pro-

tect areas subject to mechanical or chemical stresses.

p. 4|.

all

horn], the

same insoluble protein abundant

in hair

and

nails. 1.

Cell shape.

The

cells

much

of transporting epithelia are

thicker than those of exchange epithelia, so they act as a barrier as

well as

an

entry point. The cell layer

thick, but the cells are cuboidal or 2.

Membrane

columnar

modifications. The apical

is

only one

cell

the sur-

face of the cell that faces the lumen, has microvilli, fingerlike

projections that increase the surface area available

transport.

A

cell

with microvilli has

face area of a cell without

membrane,

may 3.

also

them.

at least

chemicals, bacteria, and other destructive forces, the cells in ha\ e a short

life

span. In the deeper layers,

20 times the

foi

sur-

In addition, the basolateral

cells are

them

produced

you wash your

face,

you scrub

As the skin ages, the rate of (Retin- A

).

a

off

dead

cell

cells

surface layer.

turnover declines, tretinoin

drug derived from vitamin

and surface shedding so

on the

A.

speeds up

cell

division

that the treated skin develops a

more

youthful appearance.

the side of the cell facing the extracellular fluid,

have folds that increase the

cell's

Secretory epithelia Secretory epithelia are composed

surface area.

Cell junctions. The cells of transporting epithelia are firmly

that produce a substance inside the cell

attached to adjacent cells by moderately tight to very tight

tracellular space in a process

junctions. This thelial cell

new

continually, displacing the older cells at the surface. Each time

in shape.

membrane,

Because the protective epithelia are subjected to irritating

means

on one

that material

side of the tissue

must move into an

and out of the

other in order to cross the epithelium.

cell

epi-

on the

may

be scattered

among

known

and

release

it

o\ cells

into the ex-

as secretion. Secretory cells

other epithelial

cells,

or the)

may group

together to form a multicellular gland. There are two types of cretory glands: exocrine glands

se-

and endocrine glands. 69

!

CHAPTER

3

AND

CELLS

TISSUES

Ciliated epithelium lining the airways.

(a)

(b)

Scanning electron micrograph showing

ciliated cells

mixed

with cells covered with shorter microvilli.

Cilia

Microvilli

Golgi

apparatus

Nucleus

Basement

membrane

l*3&&r

Mitochondria

Figure 3-19

Ciliated epithelia

Exocrine gland

RUNNING PROBLEM

cells

produce two types of secretions. Serous

many

secretions are watery solutions, and

Many kinds of cancer develop in epithelial cells that are subject to damage or trauma. The cervix consists of two types of epithelia.

the outside of the cervix. At the opening of the cervix, these

come

together. As Jan

lies

Mucous

exocrine secretions.

the inside of the cervix, while a protective epithelium covers

of epithelia

solutions containing glycoproteins

Goblet

cells,

shown

to take samples of cells from both inside

and outside her

cervix.

with

She then smears the

fixative.

Question

3:

cells

on

a slide

a

little

gested,

What kind of damage

or trauma are cervical ep-

and

acts as a lubricant for

epithelia

normally subjected to? Which of

more

is

its

food to be swallowed, in-

between the epithelium and the

and they produce both serous and mucous

secretory

cell,

tions. For

example, the salivary glands release mixed secretions. secretions, or

hormones,

are released

secre-

by ductless

two types of glands or single

likely to

and proteoglycans.

and microorganisms inhaled or

as a protective barrier

Endocrine ithelial cells

are

environment. Some exocrine glands contain more than one type of

and sprays them

sent to a lab for evaluation.

slides will

serous

brush

now be

The

en-

in Figure 3-20 •, are single exocrine cells that

produce mucus. Mucus

as a trap for foreign particles

and

all

mucus)

secretions (also called

sticky

on the exam-

ining table, her physician uses a small spatula

them contain

zymes. Tears, sweat, and digestive enzyme solutions are

Secretory epithelium with mucus-secreting glands lines

two types

of

be affected by trauma?

mones then

oooOoo

cells directly into

the extracellular space. Hor-

enter the blood for distribution to other portions of

the body, where they regulate or coordinate the activities

ous

tissues, organs,

ol vari-

and organ systems. Some of the best-known

endocrine glands are the pancreas, the thyroid gland, the gonads.

and the

pituitary gland. For years,

it

was thought

that

all

hor-

be onto

mones were produced by cells grouped together into endocrine glands. We now know that isolated endocrine cells occur scat-

the surface of the skin or onto an epithelium lining one of the in-

tered in the epithelial lining ol the digestive tract, in the tubules

Exocrine glands release their secretions into the external en-

vironment

\exo-,

outside + krinein, to secrete]. This

may

ternal passageways, such as the airways of the lung or the

lumen

of the kidney,

Of the intestine. In effect, an exocrine secretion leaves the body.

This

is

important to know,

cretions, like lite.

stomach

acid,

Most exocrine glands

tubes

known

as ducts.

70

you consider that some exocrine

have

a

pH

that

release theta

Sweat glands,

the breast, salivary glands, ocrine- glands.

if

tin- liver,

is

se-

incompatible with

products through open

mammary

glands found

and the pancreas

are

.ill

111

ex-

and

Figure 3-21

exocrine

•

glands.

downward

in

the walls ol the heart.

shows the

epithelial origin of

During development,

into the supporting tissms

link to the parenl epithelium in the

or

dud

glands lose the connec the bloodstream.

ting cells

and

epithelial

cells

grow

Exocrine glands retain

form of

that transports the se< ivtion to

endocrine and

its

a

a

hollow passageway

destination. Endocrine

se< rete theil

hormones

into

Tissues of the

Body

Goblet cells secrete mucus into the lumen of hollow organs such as the intestine.

Goblet

Figure 3-20

cells

CHECK

Epithelium 1

4. List

Connective tissue

Answers: p. 83

the five functional types of epithelia.

15. Define secretion.

During development, the region of epithelium destined to become glandular tissue divides downward into the underlying connective tissue.

1

Name two

6.

properties that distinguish endocrine glands from

exocrine glands. 1

7.

The

basal lamina of epithelium contains the protein fiber

laminin. Are the overlying cells attached by focal adhesions

or 18.

hemidesmosomes?

You look

at a tissue

under a microscope and see a simple it be a sample of the skin surface?

squamous epithelium. Can Explain. 1

9.

A

cell of

the intestinal epithelium secretes a substance into

the extracellular

Endocrine

Exocrine

fluid,

where

carried to the pancreas.

endocrine or an exocrine

Duct

I-i

Connecting disappear

tural

Exocrine secretory cells

picked up by the blood and cell

an

cell?

Connective Tissues Provide Support and Barriers Connective

cells

it is

the intestinal epithelium

Is

tissues, the

second major

support and sometimes

tissue type, provide struc-

a physical barrier that,

specialized cells, helps defend the

along with

body from foreign invaders

such as bacteria. The distinguishing characteristic of connective Endocrine

tissues

secretory cells

is

the presence of extensive extracellular matrix contain-

ing widely scattered Blood vessel

A

hollow center, or lumen, forms in exocrine glands, creating a duct that provides a passageway for secretions to move to the surface of the epithelium.

Figure 3-21

Development

front epithelium

The

cells secrete

and modify the matrix

of the tissue. Connective tissues range from blood, to the support Endocrine glands lose the connecting bridge of cells

them to the parent epithelium. Their secretions go directly into the bloodstream.

tissues for the skin

and

internal organs, to cartilage

and bone.

that links

Structure of Connective Tissue The matrix of connective tissue is a ground substance of proteoglycans and water in which insoluble

•

cells.

of endocrine

ami

exocrine glands

fibrous protein fibers are arranged,

much

like

The consistency of

suspended pieces of

fruit in a gelatin salad.

ground substance

highly variable, depending on the type of

is

71

CHAPTER

CELLS

3

connective

and

at the

AND TISSUES At one extreme

tissue.

other extreme

is

the watery matrix of blood,

the hardened matrix of bone. In be-

is

tween are solutions of proteoglycans that vary

in consistency

from syrupy to gelatinous. The term ground substance

some-

is

times used interchangeably with matrix.

The

Connective

if

tissue cells are described as fixed

they remain in one place, or mobile

Fixed

to place.

are responsible

and mobile found

The mobile

storage.

mainly

cells is

it

itself is

connective tissue

distinction at least

between fixed

one

cell

often indicates a

cell

that

on

either

is

down

a connective tissue cell

these suffixes should help

and

cells

name

example, are connective tissue

matrix are identified by the suffix

be given the suffix

-cyte,

-clast [klastos,

meaning

broken].

down ma-

you remember the functional difference found in bone.

ground substance, con-

In addition to secreting glycoprotein

found

gated into insoluble

duced]

in the matrix of connective tissue, aggre-

fibers.

Collagen

[kolla,

the most abundant protein in the

is

one-third of

its

dry weight.

It is

Three other protein

is

connective

fibers in

The amount and

steel.

one of the distinguishing chartissue.

connective tissue are

wavy

elastin, fib-

rillin,

and

to

original length after being stretched. This property

its

fibronectin. Elastin

as elastance. Elastin fibrillin to

sels,

and

is

a coiled,

combines with the very

form filaments and sheets of

important in skin.

elastic tissues

As mentioned

earlier,

protein that returns is

known

thin, straight fibers of

elastic fibers.

These two

such as the lungs, blood vesfibronectin connects

cells to

extracellular matrix at focal adhesions. Fibronectins also play

important role in

wound

healing and in blood clotting.

also the

Types of Connective Tissue

Table 3-4 describes in detail

the different types of connective tissue. The most

and dense connective

of connective tissue are loose

pose

tissue, cartilage,

types

tissue, adi-

bone, and blood.

Loose connective tissues that underlie skin

common

(Fig.

3-22 •) are the elastic tissues

and provide support

connective tissues are

tissues

for small glands.

whose primary function

is

Dense

strength

glue

+

human

-genes, pro-

body, almost

most diverse of the four

ligaments, and the sheaths that surround muscles and nerves. In

these tissues, collagen fibers are the

dominant

type.

Tendons (Fig. 3-23*) attach skeletal muscles to bones. Ligaments connect one bone to another. Because ligaments contain elastic fibers in addition to collagen fibers, they

have a

limit-

ed ability to stretch, whereas tendons cannot stretch.

Table 3-4: Types of Connective Tissue

TISSUE

NAME

GROUND SUBSTANCE more ground than and cells

Loose connective

Gel;

tissue

fibers

Dense, irregular connective tissue

ground

Dense, regular connective tissue

ground

Adipose

Very

More More

fibers

FIBER TYPE AND ARRANGEMENT

MAINC

Collagen,

elastic,

fibroblasts

reticular;

random

Mostly collagen; random

than

I

I

I

IVI'IN

WHERE FOUND around blood and organs, under epithelia

Skin,

vessels

Fibroblasts

Mus
>

P

1

E+F

c

C

G+H

0)

(1)

Net free energy

01 Ll_

change

Time

KEY

some

Time

Substrates

was trapped

of the activation energy

of the products. called

A

is

A

A

plot of

•. Note that the products

energy than the reactants A and

may

the bonds of glycogen during

out

energy

tion gradient.

An important

reaction

is

is

C

and

D

have

is

shown

a lower free

be given off as heat. In

is

tion is

when

(P,),

and

AIT and water Knergy

1

II

.

is

the high-energy phosphate

a

tew

to

form

metabolic reactions

energy

is

Where does the activation energy for come from? The simplest source of activation

to couple an exergonic reaction that produces energy to

an endergonic reaction that requires

of the

AH' molecule

reaction:

ADP

ATP

+

P,

—G * H

In this type of

A

plot of net free energy

G

E + F

+

H+ +

energy

+ H,

is

change

shown

is

retained by the products.

for

an endergonic reaction.

in Figure 4-4b.

Compare

this ender-

gonic reaction with the energy-producing reaction of figure 4-4a, in

which

coupled reaction, the two reactions take place

all

activation energy

added

to the reactants

was

released

during the reaction.

Some

of the energy added to an endergonic reaction remains

lizing reactions are often synthesis reactions in

made from

,ii

id I

to drive the

endergonic reaction of

F.

lowever,

coupled to trap

not always practical for reactions to be direct 1\

it is

like this.

Consequently, living

and save energy

common method

for

gy electrons carried on nucleotides molecules

NADU,

I

usually transfer

have developed waj

cells

released by exergonic reactions.

trapping energy-

is

most of

all

.

(Fig.

s

The most

form of high-ener-

in the

41].

|»» p.

\DH : and NADPH

electrons of their hydrogen atoms

trapped in the chemical bonds of the products. Thus, energy-uti-

molecules are

in

si-

the same location, so that the energy from

ATP can be used immediately

energy-Utilizing, reactions, part ol the acti-

vation energy added to the reactants

fa-

breaking the high-energy bond of ATP to drive an endergonic

I

During endergonic, or

of the most

released during this rea


vation energy, the

C +

less likely

A + B reaction shown *

D, the reverse reaction

is

it

main reasons

then so

many

A + B

is

shown

B. Reversible reactions are

that

that they are aided

is

possible,

^=^ C +

D.

biological reactions are re-

by the specialized proteins known

enzymes.

in

CHECK

Answers: p. 122

recall,

(Fig. 4-6)

What

5.

the difference between endergonic and exergonic

reactions?

the larger the acti-

that the reaction will proceed

is

6.

If

you mix baking soda and vinegar together

in

a bowl, the

reactions could be reversed with

mixture reacts and foams up, releasing carbon dioxide gas.

some

reactions have such large activa-

Name

your study of physiology, you

versible reactions.

is

in

tion energies that they are essentially irreversible. In

C + D

>

all

spontaneously. Theoretically input, but

C + D

A + B > A +

a large release of energy in the for-

has a large activation energy. As you will

enough energy

C + D

the reverse of the

was

Figure 4-4a. Because there

ward reaction A + B

is

the reaction

if

of the

activation energy of the reverse reaction. For example, look at

energy of the reaction

,

ATP

with arrows that point in both directions:

versible

activation

of

the reaction

the net free energy change of the forward reaction contributes to the

the

Energy released by exergonic reactions can be trapped in the high-energy electrons of NADH, FADH 2 or NADPH. Energy that is not trapped is given off as heat.

encounter a few

will

in this

reaction.

Do you think this reaction is endergonic or exergonic? Do you think it is reversible? Defend your answers.

7.

irre-

However, most biological reactions are

the reactant(s) and product(s)

re-

k ENZYMES Enzymes

GRAPH QUESTION

are biological catalysts, proteins that speed

Activation energy

this

rate

of chemical reactions without themselves being changed. With-

out enzymes, most chemical reactions in the an endergonic or exergonic reaction? Is

up the

slowly that the

cell

would be unable

to live. Because

not permanently changed or used up alyzes,

we might

write

it

in a reaction

A + B + enzyme This

way

-»

of writing the reaction

cell

would go so an enzyme

in the reaction that

it

is

cat-

equation this way:

C + D + enzyme

shows

thai the

enzyme

partici-

A and Bbui Is unchanged at the end ol thereA more common shorthand for enzymatic reactions shows

pates with reactants action.

the

name

of the

enzyme above

the reaction arrow, like

C+D

A + B in

this:

enzymatically catalyzed reactions, the reactants are called

substrates

Time

KEY Substrates Activation of reaction

Reaction process Products

Enzymes L€>wer the Activation Energy of Reactions How

does

.\\\

enzyme

Increase the rate ol a reaction? in thermo-

dynamic terms, H lowers the activation energy, making • Figure 4-6

90

Some rem

lions

have large

m tivation energies

likely thai the reaction

will stait

ii

Ig.

4-r»t.

I

n.

\

it

more

mes accomplish

Enzymes

of

Activation energy

without

enzyme

one million molecules of C0 2 and water to carbonic

absence of enzyme, Lower energy of

activation

presence

in

enzymes

enzyme

takes nearly 100 seconds for only

it

and water to be converted to carbonic

would go

in cells, biological reactions

would be unable

cell

3

C0 2

cule of

acid. In the

to obtain

enough energy

one moleWithout

acid.

so slowly that the

to live.

A+B

O

£

Enzymes Bind

a E

How

>.

to Their Substrates

does an enzyme bring the substrates into the best position

them

Most enzymes

to react?

are large protein molecules with

§

for

e

complex three-dimensional shapes [# p. 39]* On each enzyme molecule is a region known as the binding site, part of the protein

When

molecule that actually binds to the substrates.

en-

zyme-substrate binding takes place, the substrate molecules are

brought close to each other and to the enzyme's active

the

site,

region that promotes reaction of the substrates with each other.

Time

Activation of reaction

Reaction process Products

was thought that the binding

it

Enzymes lower the activation energy of

one another

fit

The binding

reactions

site

needs only to attract the substrates to that

region of the enzyme. Then, as the binding

ly

by binding to the reactant molecules and bringing them

to-

gether Into the best position for reacting with each other. With-

out enzymes, the reaction would depend on the random collision of the molecules to bring

them

into alignment. Notice in the

fig-

ure that neither the starting nor ending free energy content ot the substrates

The

and products has hanged.

rapid than the

same

by an enzyme

is

much more

reaction taking place in the absence of the en-

zyme. For example, consider the enzyme carbonu

which converts

C0 2 and

interaction

binding

one second

shown

is

site

to tatalyze the conversion

mally, lysosomes within cells contain

worn-out parts of the

enzyme

cell. In

enzymes

that digests specific glycolipids called gangliosides,

them

in

nerve

is

cells in

and function abnormally. Inwith Tay-Sachs disease slowly lose muscle control and

the brain, causing fants

that digest old,

Tay-Sachs, hexosaminidase A, an

absent. As a result, gangliosides accumulate

brain function.

Question

1:

They

to swell

usually die before

Hexosaminidase A

is

age

gliosides from the light-sensitive cells of the eye.

information,

what

is

more

close-

of enzyme-substrate

According to

this

model, the fit ei-

would en-

enzyme to bind to either reactants or products and thus

be able to catalyze i.

do

.in

a single

this.

Induced

fit

explains reversibility better than

model,

the older lock-and-kej

matched

reaction in both directions. In tact, en-

in

which the binding

site

was

to either the substrates or the products, but not to both.

Enzyme

Most enzymes

Specificity

react

with only one

of substrates or with a

group of similar substrates. The

ad enzyme to catalyze

a

is

certain reaction or a

called specificity,

ability of

group of closely

some enzymes

set

re-

are very spe-

about the reactions that they catalyze. For example, the sole

enzyme glucokinase is to attach a phosphate group onto glucose molecules when they enter a cell. Other enzymes act on whole groups ot molecules. The enzymes known as peptidases function of the

ad on peptide bonds of polypeptides without regard for which two amino acids are joined by those bonds. Peptidases therefore are not very specific in their action.

An Enzyme's Name

four.

also required to

in figure 4-8b.

model

fit

ther the substrate or the product molecules. This trait

able an

cific

a particularly devastating condition. Nor-

is

and the substrates

has an intermediate shape that can change to

lated reactions

RUNNING PROBLEM Tay-Sachs disease

site

changes shape to

ahhydrase,

water to carbonic add. A single molecule

of carbonic anhydrase takes

site

to the substrates. This induced-fit

zymes

(

rate of a reaction catalyzed

was

exactly.

begin to interact, the binding this

site

fit the substrates exactly, the way a key fits into a lock. A representation of this lock-and-key model of enzyme activity is shown in Figure 4-8a». In recent decades, however, scientists have discovered that the binding site and the substrates do not

need to Figure 4-7

years,

shaped to Substrates

•

many

For

KEY

remove ganBased on

this

Function function in

Gives Information About Its Most enzyme names are important clues to their a cell. The names of most enzymes are instantly

another symptom of Tay-Sachs disease

besides loss of muscle control

and brain function?

oCjo © ©®

•Recently, researchers discovered that

R\

\

can sometimes

act as a catalyst.

91

CHAPTER 4 CELLULAR METABOLISM

(a)

Lock-and-key model In this

Binding

older model, the

site

site

was an exact match

for the substrates.

/

\ ENZYME

(b)

enzyme binding

^^

\

model

Induced-fit

model, the enzyme binds most tightly to an intermediate form of substrate or product. This model compatible with reversible reactions that are catalyzed by one enzyme. In this

is

more

Intermediate form

•

Two models of enzyme binding sites

Figure 4-8

recognizable by the suffix

name

-ase.

The

first

of reaction, the substrate

upon which the enzyme

acts, or

both.

For example, glucokinase, mentioned previously, has glucose as

and

substrate

as a kinase

substrate. Addition of a

adds a phosphate group

phosphate group

is

called

[

$

its

p. 28] to the

phosphorylation.

The peptidases mentioned above break up peptides into smaller peptides or

amino

amino

Enzymes and

part of the enzyme's

(everything that precedes the suffix) usually refers to the type

acids by cleaving the peptide

bond

that links the

a

hours following a heart attack, damaged heart muscle

enzymes into the blood. One way son's chest pain

role in the

cells release

determine whether is

Some

a per-

to look for el-

diagnosticalh

important enzymes and the diseases of which they are suggestive are listed in Table 4-2.

CHECK

for

8.

different digestive

enzymes, are examples of older enzyme

names.

A few enzymes come

known

as

alyze the

isozymes

same

ut tissues.

I

[iso-,

10. in a variety oi related forms, these are

equal].

Isozymes

are

enzymes

several isozymes, Including

and

a se


8

"5

0)

a>

rr

DC

20

40

30

50

Temperature This

60

5

6

7

PH

f'C)

enzyme

Most enzymes humans have

denatures around 50° C.

in

optimal activity near the body's

GRAPH QUESTION

internal Is

the

at

30

pH

GRAPH QUESTION

of 7.4.

enzyme more active C or at 48" C?

If

Figure 4-12

Effect of

pH and

The

marinated

is

hydrogen ions that

acidic lime juice contains

bonds

rupt hydrogen

muscle proteins of the

in the

fish,

in

dis-

causing

the proteins to lose their configuration. As a result, the meat be-

comes more firm and opaque,

just as

it

would

if it

were cooked

pH and enzymes

crease the activity of

changes exceed some altered so

the

its

much

enzyme

restored

if

is

temperature can increase or de(Fig.

critical point,

that

its

activity

is

4-12 •). However, once the

the structure of the destroyed.

said to be denatured. In a

the modulator

original shape as

denaturation

way

is

a

if

few

When

enzyme

is

this occurs,

cases, activity

can be

removed. The protein then resumes

is

nothing had happened. Usually, however,

permanent

to unfry an egg or

loss of activity.

uncook

There

is

certainly

no

and pH on enzymes and other

one reason that these

factors are so closely regulated

is

falls

from 8 to

7.4,

to the activity

enzyme?

line to chat with his girlfriend, the cashier.

buying

a ticket, but

from getting

he prevents the people

in line

interest in

behind him

their tickets for the movie.

Allosteric

modulators

shape)) bind to the

[alio-,

other +

stereos,

(

1

)

site (Fig.

binding

activity. Allosteric

site for

gen-binding

ability

changes with

allosteric

in

of

a

and

increase the probability of enzyme-sub-

Chapter 18 you the

(2)

decrease the

the substrate and inhibit

modulation also occurs

enzymes. For example,

site

(as

4-14 •). This type of

binding and enhance enzyme activity or

affinity of the

solid

enzyme away from the binding

modulation can either strate

He has no

respiratory

enzyme

in proteins other will learn

protein

how

than

the oxy-

hemoglobin

modulation by carbon dioxide,

H\ and

several other factors.

a piece of fish. The potentially dis-

astrous influence of temperature

proteins

of the

change the shape of the binding

with heat. Small changes in

pH

temperature on enzyme activity

ceviche, the national dish of Ecuador, raw fish

lime juice.

the

what happens 1

•

9

8

A competitive inhibitor blocks substrate binding at the binding site.

by the body.

Chemical Modulators that bind to

enzymes and

Chemical modulators are molecules alter their catalytic ability.

There are

three types of chemical modulators: competitive Inhibitors,

al-

Binding site

losteric

modulators, and covalent modulators.

Competitive inhibitors bind to the enzyme site,

blocking the

site

at its

and thus preventing the substrate from

binding with the enzyme

(Fig.

4-13 •).

hibitors are alternative substrates that

Some

competitive

and block the binding are like the

guy

site

who

without being acted upon slips into

in-

can also be acted upon by

the enzyme. Others are simply molecules that bind to the

They

binding

enzyme

themselves.

the front of the movie ticket

Figure 4-13

Competitive inhibition 95

w

CHAPTER 4 CELLULAR METABOLISM

(a)

Allosteric activation

Binding site

Allosteric activator

Modulator binds to enzyme away from active site.

Enzyme without modulator inactive.

is

(b)

Enzyme

with

modulator

is

bound active.

Allosteric inhibition

Binding site

Allosteric inhibitor

Modulator binds to enzyme away from binding site and decreases enzyme-substrate binding.

Enzyme without modulator active.

is

Figure 4-14

Allosteric

modulation

CHECK

Covalent modulators are atoms or functional groups that use covalent bonds to bind to enzymes and alter the enzymes' 1 1

properties. Like allosteric modulators, covalent

either increase or decrease the activity of the

most

common

Many enzymes when

covalent modulators

.

may

on and

off or

processes

the phosphate group.

1

2.

Match the modulator

penicillin.

Allosteric

1.

Bind by covalent bonds

Competitive

2.

Bind away from the binding

(c)

Covalent

up and down allows the

3.

Bind to the binding

and

4.

Inhibit activity only

5.

Inhibit or

noticed that Penicillium mold inhibited bacterial growth.

from the mold and used

it

a< ttve

ingredient penicillin

to treat infections in

humans. Yet

until 1965 that researchers figured out exactly

antibiotic works. Penicillin

to a key bacterial so,

it

unable to make

is

a

tli.it

how

it

the

competitive inhibitor that binds

enzyme by mimicking

forms bonds

verslbly Inhibits the

the normal substrate, in

are unbreakable

and thereby

irre-

enzyme. Without the enzyme, the bacterium

a rigid tell wall.

terium swells, ruptures, and dies

96

action(s).

its

site

enhance

site

activity

known chemical modulators is the antibiotic Alexander Fleming discovered this compound in 1928,

By 1938, researchers had extracted the

is

to

of the best

when he

doing

enzymatic reactions that an enzyme

(b)

energy-producing pathways.

was not

22

affect.

(a)

regulate the flow of biomolecules through synthetic

One

in

1

enzyme. One of the

phosphate group forms a covalent bond with them. The

a

Name two

modulator can

can be either activated or inactivated

in the cell

ability to turn reactions cell to

is

modulators

Answers: p.

Without the

rigid wall, the bat

Enzyme anil Substrate Concentration Affect Reaction Rate We ther

measure the

how

fast

strates are fa< tois,

rate ot

an enzymatic reaction

the products are synthesized or

consumed. Reaction

rate

can

how

fast

a

ei-

the sub-

number

ol

amount ot enzj me mammals we consider

including changes In temperature, the

he

temperature

to

amount and

substrate concentration as the

.it

monitoring

w altered in

present, or the substrate concentration. In

th.it

In

iii

t

essentially

reaction rate.

constant,

[his

two

leaves

mam

enzyme variables

,

Enzymes

Reaction Rate Is Directly Related to the Amount of Enzyme Present Enzyme amount is a major determinant of the rate of an enzymatic reaction.

there

is

no enzyme, most

enzyme is present, the rate be proportional to the amount of enzyme.

metabolic reactions go very slowly. of the reaction will

If

If

The graph in Figure 4-1 5 • shows the results of a typical experiment in which the amount of substrate remains constant while the crease in

GRAPH QUESTION

amount of enzyme is varied. As the graph shows, an inthe amount of enzyme present causes an increase in the

rate of the reaction.

As an analogy, think of the checkout lines in a supermarket.

Imagine that each cashier are substrates,

there are in

means

an enzyme, the waiting customers

and those leaving the

store with their purchases are

25

a

that

reaction, the presence of

more binding

In this

At the

more enzyme molecules

sites are available to interact

with the

75

50

100

125

150

175

*

Substrate concentration (mg/ml_)

One hundred people will get checked out faster when 25 lines open than when there are only 10 lines. Like-

products.

wise,

is

•

experiment, the amount of rate the enzyme

maximum

Figure 4-16

substrate molecules. As a result, reactants are converted into

enzyme was

constant.

said to be saturated.

is

Effect of changing substrate concentration

on

rate

products more rapidly.

Regulating

enzyme concentration

an important strategy

is

that cells use to control their physiological processes. Cells

amount

enzyme by influencing both its synthesis and its breakdown. If enzyme synthesis exceeds breakdown, enzyme accumulates and the reaction catalyzed by the enzyme speeds up. If enzyme breakdown exceeds synthesis, the amount of enzyme decreases, as does the reaction rate. Even when laamount of enzyme is constant, there is still a steady turnover of enzyme molecules. alter the

of an

tional to the substrate concentration. But

once the concentration

beyond

a certain level, the en-

of substrate molecules increases

zyme molecules have no more binding sites free molecules. The enzyme is catalyzing reactions and the

tration of

enzyme

is

If

cording to the concentration of substrate, figure

tration

is

the concen-

constant, then the reaction rate will vary ac-

the results of a typical experiment In which the

4- 16

• shows

enzyme concen-

constant, but the concentration ol substrate varies. At

low substrate concentrations, the reaction

rate

is

sion

directly propor-

Q.

3

belt In

Initially,

GRAPH QUESTION

the belt

Q. O!

What is the rate when the enzyme concentration is equal to A?

g C o o «

When

*-•

the rate

enzyme

what

the concentration?

was bringing canch

mouth

i

DC

i

i

r

A B C Enzyme concentration In this

rapidly,

to he a so fast that she couldn't

pack

it

maximum

rate.

That

was working

she'

at

her

point. (Her solution

was to

all

canch

stuff the

as well as into the box!)

Answers: p.

What happens to the rate of an enzymatic enzyme has reached saturation?

reaction

Reversible Reactions he stud]

into

when

1

22

the

Obey the Law of Mass Action

ol reaction rates in cells

is

complicated by the

fact that

is

o

Ba

more

14.

is

little

to increase her packing speed to keep up. Finally, the

reaction as the

I

2.5 mg/sec,

televi-

it

What happens to the rate of an enzymatic amount of enzyme present decreases?

Ei

can,

on the con-

3.

1

-

days of

removing the candy and putting

difficulty

the boxes because

E

oo

it

was moving slowly,

CONCEPT CHECK

-

some reactions tion A + B

are reversible. This *

C

+

D

In the reverse reaction,

—*

means

that the forward reac-

can reverse, so that the products

become the products.* What then determines in which

C + D

become

A

*

B.

the reactants and

the reactants

direction the reaction

is

to

experiment, the substrate amount remains constant.

go? The answer Figure 4-15 rate

in the early

ucy show. Lucille Ball was working

was Lucy's saturation

0)

•

/

the box. Gradually, the belt brought candy to her

and she had

T3

o 2

(Mr

and she had no

(0 k_

/ /

as fast as

value. This condition

veyor belt of a candy factory, loading chocolates into the

Into her

o r2 (Some of the added substrate is converted into product.)

A+B

two

have

lower-than-normal

enough

(c)

who

um

D

the substrate and product concentrations until the equilibri-

ratio

is

restored.

The law

of mass action

is

important

in

phys-

iology because as the concentration of substrates changes, the r,

The

change

substrates to products

ratio of

always the same

is

•

=r2

is

reflected in the concentrations of the products.

Enzymatic Reactions Can Be

at equilibrium.

Categorized Law

of mass action Although this figure shows the amount of A + B equal to C + D at equilibrium, the actual ratio can vary, depending on the reaction. Figure 4-17

Most reactions catalyzed by enzymes can be

classified into

four categories: oxidation-reduction, hydrolysis-dehydration, ex-

change-addition-subtraction, and ligation reactions.

equilibrium, where the rate of the reaction in the forward direction (A + B

*

reaction (C

+ D

C + >

equilibrium, there

product. As

fast as

tion takes place:

D)

A +

in the

B),

as

shown

no net change A and B convert

is

C and D

amount

in the

to

C and

turn back into

4-17a#. At

in Figure

of reactant or

D, the reverse reac-

A and B

an equal

at

rate.

some factor disturbs this equilibrium by the amount of A and B within the system? You learned

But what happens increasing

exactly equal to the rate of the reverse

is

strate concentration.

If

is

proportional to sub-

A and

the concentration of

tem goes up, so does the

rate of the

B in the sys-

forward reaction

Oxidation-Reduction Reactions

are converted into products

the reaction

reversible, as the

is

so does the rate

and

l

and

it

rea


anhydrase

the abbrevia-

(c)

(b) -*

Some,

P, is

If

Many enzymes cell.

(= ATP)

bond and

tions transfer that energy to the high-energy

Cell

reac-

phosphate bond and

ADP^P

indicates a high-energy

more important

bond energy

Enzymes Within the

third phosphate

pounds) of ATP to support one day's worth of metabolic

versible (Fig. 4-20c).

Isolation of

molecule con-

broken during removal of the phosis

+ energy

ergy storage molecule.

forward and one for the reverse reaction,

can regulate the reaction more closely dig. 4-20b).

a nucleotide

range from 7 to 12 kcal per mole of ATP.

cannot be closely regulated except by modulators and by control enzymes, one

is

bond

of free energy released by breaking a

termined by the law of mass action. These reactions therefore

of the

often

tion for an inorganic phosphate group. Estimates of the

and direction of metabo-

reaction in either direction

will

The squiggle

Cells can use re-

enzyme can run the

4-20a#), the reaction

when

ADP +

called end-product inhibition.

Enzymes and Reversible Reactions

ATP

stored in this high-energy

is

phate group. This relationship

sometimes

is

terms of the net amount of adenosine triphosphate, or

in

taining three phosphate groups |tf p. 40).

proceeds and Z accumulates, the enzyme catalyzing the conversion of

of metabolic pathways as suppliers of energy

ATP, that the pathways can yield.

an inhibitory modulator of the pathway. As the pathway

acts as

Transfers Energy Between Reactions

1

t

Reversi

reaction

enzymes

1

rreversible in

r

Most

ami

irreversible

cells of

meta-

the body can

f

Glucose 6-phosphate

Glucose 6-phosphate

requiring rwi 3

Reversible

bolic reactions

eaction goes

only on g direction

phosphorylate glucose to glucose 6-phosphate make glucose by dephosphorylation, because they lack the enzyme glucose 6-phosphatase to. The liver ami kidney are the primarj but cannot

sites for

glucose synthesis

(b).

101

CHAPTER 4 CELLULAR METABOLISM

Glucose

• • 4 N A V

GATOR

!

G L

Y C

Glycerol

ADP

O

ATP

L

Y S

Amino acids

This icon represents the

I

s

different steps in the

r

metabolic

Look

for

it

summary in

that follow to help

Amino

navigate your

Pyruvate

Acetyl

Fatty acids

you

way through

metabolism.

Cytosol

acids

figure.

the figures

Mitochondrion

CoA

CHECK 1

6.

Name

five

ways that

Answers: pp. 122-123

regulate the

cells

movement

of

substrates through metabolic pathways. 1

7.

what

In

Amino

ATP

part of the molecule does

energy?

In

what

and

trap

part of the molecule does

store

NADH

store

energy?

acids 1

8.

What

the difference between aerobic and anaerobic

is

pathways?

k ATP PRODUCTION High-energy electrons

andH+

The

catabolic pathways that extract energy from biomolecules

and

transfer

it

ATP

to

are

summarized

production of ATP follows two the

citric

small

in Figure 4-21

common

•. Aerobic

pathways: glycolysis and

acid (tricarboxylic acid) cycle. Both pathways produce

amounts

of

ATP

directly,

but their most important contri-

butions to ATP synthesis are high-energy electrons carried by

NADH

FADH 2

and

to the electron transport system in the mito-

chondria. The electron transport system, in turn, transfers energy

from the electrons to the high-energy phosphate bond of ATP. At various points, the process produces carbon dioxide and water.

Overview of aerobic pathways for ATP production ATP can be made through aerobic pathways using the chemical bond energy from glucose, amino acids, or glycerol Figure 4-21

and

fatty acids.

The water can be used by the cell, but carbon dioxide product and must be removed from the body. All three types of

drates, proteins, citric

and

is

a waste

biomolecules used for energy (carbohy-

lipids) use the

enzymes of

glycolysis, the

acid cycle, and the electron transport system to produce

ATP. Carbohydrates enter the pathways in the form of glucose. Lipids are broken

The metabolic pathways

that yield the most

ATP molecules

are those that require oxygen, the aerobic, or oxidative, pathways.

Anaerobic

[an-,

without +

tier,

air]

pathways that can proceed

without oxygen also produce ATP molecules, but er quantities.

that

The lower ATP

yield of anaerobic

we

will

consider

how

small-

to survive for

In the tiexl se
UAA Stop UAG

e

Leu

CULT)

c o "D O O

CUA cugJ

auaJ AUG

Stop

UGG

Trp

[

AUlTl AUC y He

TO

UGA

CGC Urg y CGA cggJ

Pro

f

-O

CyS

mRNA

CGlT|

CUCUeu

If)

UGU\ UGC/

3;

Met

DNA template

How does the cell know which of the thousands of base pairs DNA to use to make a strand of mRNA? turns out that the inIt

needs to make

Q. cr

formation a

a>

segment of

DNA known

contains

the information needed to

o o Q. O 3

Thr

of

+

Star!

all

mRNA. We

cell

a

as a gene.

protein

is

contained within

a

A gene is a region of DNA that make a functional piece of

used to believe that a gene coded for only one protein

one gene-one protein theorx gene can create main proteins. (the

i,

but

we now know

that

one

GUlTl

GUcUal GUA GUGj

Alternative Splicing Creates Multiple Proteins from One Sequence of DNA

Ala

[

ihe gene

Thegenetii code rhis table shows the genetic appears in the codons ol mRNA. he three-lettei

Figure 4-31

code

as

it

I

112

tor the

is

,1

nucleotide string that Includes the codon

polypeptide to be synthesized,

.is

well as

se-

some

1

abbreviations to the right ol the brackets Indicate the amino a< ids thai these codons represent. he starl and stop codons arc also marked.

quence

itseit

noncoding

segments,

cleotides as

i

I

his allows

.i

oiling or

i

he

designation

noncoding

single piece ol

I

>N

\

is

ol

sequences

not fixed

to create

foi

a

ol

nu-

given gene.

more than one protein

Synthetic Pathways

RNA

polymerase binds

The section of DNA the gene unwinds.

RNA

A\£\d\0\d\0X0\0%.

DNA.

to

A^Xf^Xf

that contains

nucleotides bind to DNA,

creating a single strand of

^W yn

mRNA.

#%#%#%#%,


Post-translational

continues

Lf

p, Proteins that

packaged

I.?

in

modification

the Golgi.

in

will leave the cell are secretory vesicles.

Proteins that remain

f

packaged

in

in

the

cell

are

Golgi apparatus

lysosomes or storage

vesicles.

Proteins secreted

Cell

•

into extracellular

Figure 4-35

mul

space

Post-translational modification the secretory puth\su\

RUNNING PROBLEM CONCLUSION Tay-Sachs Disease In this

down

running problem you learned that Tay-Sachs disease gangliosides

also learned that a

in cells

blood

is

missing.

test

in

27 Americans

is

an incurable, recessive genetic disorder

of Eastern

European Jewish descent

in

in

which the enzyme that breaks

gene

carries the

can detect the presence of the deadly gene. Check your understanding of

summary table. more on Tay Sachs disease, go to the website

paring your answers to those

To read

One

this

You have

for this disorder.

running problem by com-

the

of the National Tay Sachs

&

Allied Diseases Association (www.ntsad.org) or see

"Tay-Sachs Disease Carrier screening, prenatal diagnosis, and the molecular era. An international perspective, 1970 to 1993" journal of the American Medical Association

QUESTION What

is

another

(1

9):2307-231

5,

Nov.

1

7,

1

symptom

of

muscle control and brain

INTEGRATION

function?

Hexosaminidase A breaks down

Damage

could cause vision problems and even

enzyme

blindness.

absent and gangliosides

accumulate cells of

in cells,

JAMA,

AND ANALYSIS

gangliosides. In Tay-Sachs disease, the is

in

993.

FACTS

Tay-Sachs disease besides loss of

270

to light-sensitive cells of the eye

including light-sensitive

the eye, and cause

them

to function

abnormally.

How

could you test whether

Sarah and David are carriers of the Tay-Sachs gene?

Carriers of the levels of

gene have lower-than-normal

hexosaminidase

A.

Run

tests to

levels in

people

who

disease)

determine the average enzyme

known and

carriers of the disease

have had in

people

of being carriers.

(i.e.,

children with Tay-Sachs

who

Compare

have the

little

likelihood

enzyme

levels of

suspected carriers to the averages for the

known

carriers

and

noncarriers.

(continues on next page)

117

CHAPTER 4 CELLULAR METABOLISM

QUESTION

FACTS

INTEGRATION The new

Tay-Sachs disease more

The new test detects the defective gene. The old test analyzed levels of the enzyme

accurate than the old test?

produced by the gene.

Why

is

the

new

test for the

test

is

AND

ANALYSIS

a direct

The old

way

to test

was an

if

a person

indirect way.

is

a carrier.

is

possible for factors other than a defective

gene to think of

test

It

enzyme level. Can you some? (See answers at end of alter a person's

chapter.)

The Tay-Sachs gene recessive

gene

carrier

and

Tt

a

What

(t).

chance that any

is

is

the

x TT

Each child has

a

50%

chance of being

a carrier

(Tt).

I

TTTtTTTt

child of a

a noncarrier will

be a carrier?

O © O © ® d) CHAPTER SUMMARY The major theme

of this chapter

acquired, transferred,

and used

biological energy

is

to

do

and how

it is

biological work. Energy

and glycogen and

stored in large biomolecules such as fats

is

is

ex-

from them through the processes of metabolism. Reacand processes that require energy often extract it from the high-energy bond of ATP, a pattern you will see repeated as you learn more about the organ systems of the body. Two other themes in the chapter involve different kinds of structure-function relationships: molecular interactions and com-

tracted tions

which

depend heavily on molecular shapes. two models of enzymesubstrate interaction, the older lock-and-key model and the newer induced-fit model. (Note that as new models are presented, they may either displace an older model or become an alternative their substrates,

also

For example, this chapter presented

model.)

The final theme presented is compartmentation of enzymes, which is essential for organizing and separating metabolic processes. Glycolysis takes place in the cytosol of the

cell, for

partmentation. Molecular interactions are important in proteins,

ample, as does the anaerobic metabolism of pyruvate to

where the function of a protein often depends on its folding into the proper shape, and in the interactions between enzymes and

The

citric

ex-

lactate.

and the electron located on the inner mitochondrial membrane.

acid cycle occurs in the mitochondria,

transport chain

is

Energy in Biological Systems 1

.

Energy is the capacity to do work. Chemical work enables and organisms to grow, reproduce, and carry out normal

2.

activities.

Transport work enables

create concentration gradients.

movement,

cells to

Kinetic energy stored energy,

cells

is

the energy of motion. Potential energy

is

(p. 86; Fig. 4-2)

move molecules to

Mechanical work

is

used for

(pp. 85-86)

Clientical Reactions 5.

4.

A chemical reaction begins with one or more reactants and ends with one or more products. Reaction rate is measured as the change in concentration of products with time. (p. 88)

7.

bonds of a molecule and the free energy of the molecule.

8.

The energy

stored in the chemical

available to perform (p.

work

is

gonic reactions,

88)

Activation energy

is

the

input ol energy required to

initial

hc-^in a reaction, (p. K8; Fig. 4-3) 6.

Exergonic reactions arc energy producing. Endergonic actions are energy utilizing,

118

(p.

K

l

;

»;

I

ig.

4-4)

re-

Energy (p.

9. 5.

Metabolic pathways couple exergonic reactions to ender-

A

(p.

89)

for driving

endergonic reactions

is

stored In ATP.

89) reaction that can proceed in both directions

is

called a

one direction hut not the other, it is an irreversible reaction. The net hange oi a rea< don determines whether that retree energj reversible reaction.

It

a reaction

i

action tan be reversed, (pp. 89

l

>0)

can proceed

in

1

1

Chapter Summary

Enzytnes 10.

Enzymes

are biological catalysts that speed

up the

rate of

15.

chemical reactions without themselves being changed. Enzymes bind to reactant molecules, bringing them together into the best position for reacting with each other. In reac-

by

catalyzed

tions

enzymes,

the

reactants

are

decrease the activation energy of the reaction, (pp. 95-96; Figs. 4-13 and 4-14)

called

substrates, (p. 90) 11.

enzyme that binds to the substrates is called the binding site. The induced-fit model of enzyme-sub-

The

part of the

binding site has an intermedishape that can change to fit either the substrate or the product molecules, (p. 91; Fig. 4-8)

16. Factors that affect the rate of

1

2.

Specificity

is

the ability of an

enzyme

to catalyze a certain re-

action or a group of closely related reactions,

(p.

17.

When an enzyme is saturated with maximum possible rate. (p. 97)

Some enzymes

are

be activated. This

91)

14.

Enzyme

Fig.

the reaction,

(p.

is

when

a reaction

the ratio of substrates to products

4-10)

by temperature, pH, and modulamodulator changes the ability of the entor molecules. A zyme to (1) bind the substrate or (2) alter activation energy of activity

works

at its

go to a state of equilibrium, where the forward direction is exactly equal of the reverse reaction. Reversible reactions obey

the law of mass action:

require the presence of a cofactor. Or-

ganic cofactors are called coenzymes, (pp. 93-94;

it

rate of the reaction in the

produced as inactive precursors and must

may

substrate,

18. Reversible reactions

to the rate 13.

enzymatic reactions include

modulation, the enzyme concentration, and the ratio of the concentrations of substrates and products, (p. 96)

strate interaction says that the

ate

Competitive inhibitors block the binding site of the enzyme directly. Allosteric modulators bind to the enzyme away from the binding site and change the shape of the binding site. Covalent modulators affect the ability of an enzyme to

is

is

at equilibrium,

always the same.

If

the

concentration of a substrate or product changes, the equilib-

rium

altered

19.

will

be disturbed,

(p.

Most reactions can be hydrolysis-dehydration,

98; Fig. 4-17)

classified

as oxidation-reduction,

addition-subtraction-exchange,

or ligation reactions, (pp. 98-99; Tbl. 4-4

94)

Metabolism 20. All the chemical reactions in the

body

are

known

enzymes to catalyze reversible reactions, (4) isolating enzymes within intracellular organelles, or (5) maintaining an optimum ratio of ATP to ADP. (p. 100) ferent

collectively

metabolism. Catabolic reactions release energy and down large biomolecules. Anabolic reactions require a net input of energy and synthesize large biomolecules. (p. 99)

as

break

22.

through their metabolic pathways by (1) controlling the enzyme concentration, (2) producing allosteric and covalent modulators, (3) using dif-

21. Cells regulate the flow of molecules

Aerobic pathways require oxygen and yield the most ATP. Anaerobic pathways can proceed without oxygen, but produce ATP in much smaller quantities, (p. 102

ATP Production interactive

//'

Phonology

25. Aerobic

Muscular: Muscle Metabolism

metabolism

of pyruvate

through the

citric

acid

cycle yields ATP, carbon dioxide, water, and high-energy electrons captured bj 23.

Through glycolysis, one molecule of glucose is converted into two pyruvate molecules, two ATP, two NADH, and two H*.

Glycolysis does not require the presence of oxygen,

(p. 103; Fig.

4-22)

metabolism, pyruvate is converted into lactate with a net yield of two ATP for each glucose molecule,

(p.

105; Fig. 4-24)

106; Fig. 4-25)

Glycogen and

lipids are the

primary energy storage moledown for ATP production

cules in animals. Lipids are broken in the process of

104; Fig. 4-23)

Synthetic

27.

and FAHH-

High-energy electrons from NADH and FADHi give up their energy as they pass through the electron transport system. Their energy is trapped in the high-energy bonds of ATP (p.

24. In anaerobic

(p.

26.

NADH

beta-oxidation,

(p.

109; Fig. 4-28)

Pathways

28. In gluconeogenesis,

verted to glucose,

(p.

amino 1

acids

and

10; Fig. 4-29)

glycerol can be con-

29. Fat Fig.

and cholesterol synthesis requires

acetyl

CoA.

(p.

Ill:

4-30)

119

.

CHAPTER 4 CELLULAR METABOLISM is controlled by nuclear genes made of DNA. The nucleotide code from a gene is transcribed into a matching code on messenger RNA (mRNA). Alternative

30. Protein synthesis

splicing of

mRNA in

The

mRNA goes

vert the (p.

may

33. Proteins

4-33)

Fig.

to the cytoplasm and, with the assistance of

RNA

and ribosomal RNA, assembles amino acids into the sequence designated by the gene. This process is

transfer

116)

the nucleus allows one gene to code for

multiple proteins, (pp. 112-114; 31.

and protein folding connewly synthesized protein to its finished form,

32. Post-translational modification

be modified in the rough endoplasmic reticu-

lum

or the Golgi apparatus. In the Golgi, they are packaged

into

membrane-bound

vesicles that

age vesicles, or secretory vesicles,

become lysosomes,

(p.

stor-

116; Fig. 4-35)

called translation, (pp. 112-114; Fig. 4-34)

QUESTIONS iMawMifc.-ftiir^i.nfjg 1

List

the three basic forms of work and give a physiological ex-

10

ample of each. 2.

protein

tivity

Explain the difference between potential and kinetic energy.

3. State

A

own

the two laws of thermodynamics in your

whose

structure

destroyed

is

altered to the point that

is

said to be

is

its

ac-

.

words.

an oxidation-reduction reaction, where electrons are molecules, the molecule that gains an electron is said to be and the one that loses an elec-

obtain

tron

11. In

moved between

,

4.

The sum of all chemical processes through which and store energy is called

cells

is

.

.

5.

In the reaction

12.

C0 2 + H 2

dioxide are the

,

cause this reaction

H2CO3. water and carbon

»

and

H 2 CO s

propriate to call water

the product. Be-

is

The

up chemical

all

re-

terms are

(b)

(c)

(d)

14. In

in the

2.

endergonic

of large biomolecules. In

the part of a protein

3.

activation energy

gy of metabolism?

molecule that actually binds the substrates

4.

reversible

5.

irreversible

a reaction that releases

6.

energy

7.

induced binding

the ability of an

enzyme

one reaction

fit

product of a metabolic

(the

.

site

8.

specificity

9.

free

10

saturation

how H + movement

16. Explain

energy

membrane

boost of energy needed

17. List the

results in

two

carrier

ATP

across the inner mitochondrial

synthesis.

molecules that deliver high-energy elec-

trons to the election transport system.

the ability of a protein 18.

its

Since 1972, fix

enzymes have been designated by adding the to their name.

sufi i

2+

thai must be presenl in order for an enzyme to work is called a _ Organic mole cules thai must be presenl for an enzyme to function are called rhe precursors of these organic molecules in our diet. come from ion,

such as Ca

or

Mg'

.The termed _ fatt) acids are broken Into two-carbon acetyl CoA molecules In a pathwaj called _. Which pathway do these acetyl CoA molecules join in order to produce ATP?

The breakdown

of lipids for energy

is

long chains of

of the substrate

>.

1

low

many

proteins,

,

.

120

last

end product) accumulates and slows or stops reactions earlier in the pathway is called

shape to fit more closely with that

An

Metabolic regulation where the

pathway

result

and reacand result in the synthesis what units do we measure the ener-

in either direction

15.

and

large biomolecules,

tions require a net input of energy

to alter

9.

breakdown of

exergonic

to get a reaction started

8.

reactions release energy

metabolism,

1.

but not another

(f)

.

a reaction that can run

to catalyze

(e)

)

.

used): (a)

called

amino group (NH 2 from a molecule (such an amino acid) is called Transfer of an amino group from one molecule to the carbon skeleton of another molecule (to form a different amino acid) is called What happens to the amino group removed from an amino acid?

of the reaction. their definitions (not

is

polymers, such as

.

as

often expressed as molarity/second.

Match these terms with

called

down

13 The removal of an

called the reaction

actions by (increasing or decreasing?) the activation energy

7.

is

to break

also ap.

are protein molecules that speed

6.

starch, it is

and carbon dioxide

speed at which this reaction occurs ,

is

from reacting molecules

H2

Using

.

catalyzed by an enzyme,

is

The removal of H 2

20.

Which

kilocalories per

and

gram

are stored In carbohydrates,

.'

t.its.

respectively

cellular organelles are Involved In lipid synthesis?

S

Chapter Summary

LEVEL TWO Reviewh maps using the following

21. Create

Map acetyl

Map

Metabolism

1:

CoA

amino ATP

gen ion concentration

terms. 2:

gradient.

Protein synthesis

Proteins are modified in the endoplasmic reticulum. Metabolic reactions are often coupled to the reaction

(c)

alternative splicing

base pairing

acids

(d)

DNA exon gene

citric acid cycle

co2 cytosol

initiation factors

ADP +

>

Pj.

proteins have S

—

bonds between nonadjacent

electron transport system

intron

FADH2

mRNA mRNA

fatty acids

ATP Some

(e)

amino acids. Enzymes catalyze

processing (f)

gluconeogenesis

nucleotides (A, C, G,

glucose glycerol

promoter RNA polymerase

glycogen

sense strand

glycolysis

start

high-energy electrons

codon stop codon

lactate

transcription

T, A,

biological

reactions.

U)

modulators change the binding site of enzymes. Allosteric

(g)

24. Define, compare,

and contrast the following terms: competi-

tive inhibition, allosteric

modulation, covalent modulation.

why

25. Explain

enzyme

in

it is advantageous an inactive form.

for a cell to store or secrete

an

mitochondria

NADH

26.

pyruvate water 22.

When bonds are

broken during

a

chemical reaction, what are

27.

those bonds?

ic

processes.

tion.

29.

Glycolysis takes place in the

1.

Biological energy

is

yields

and H 2

the advantage of converting glycogen to glucose 6-

cytoplasm; oxidative phos-

2.

Compartmentation

phorylation takes place in the

3.

Molecular interactions

Which

On what

and

transla-

organelles are involved in these processes?

molecule does the anticodon appear? Explain the molecule in protein synthesis.

role of this

mitochondria. (b)

What

CO z

28. Briefly describe the processes of transcription

Match the following theme(s) with the appropriate metabol(a)

from the aerobic breakdown of to the yield from one glucose going through anaerobic glycolysis ending with lactate. What are the advantages each pathway offers? to

phosphate rather than to glucose?

the three possible fates for the potential energy found in

23.

Compare the energy

one glucose

oxygen

The electron transport system traps energy in a hydro-

50.

Is

31.

If

\

1' 1

ATP

,in

example of potential or

releases

kinetic energ\

'

energy to drive a chemical reaction, would

you suspect the activation energy of that reaction

to be large

or small? Explain.

LEVEL THREE P 32. Transporting epithelial cells in the intestine

cose as their primary energy source.

do not use

glu-

What molecules might

they use instead? 33.

34.

t

in the right

for the reaction

A

list

+ B

column shows the *

D.

Is

this

free

mRNA codon

and

the appropriate anticodon.

DNA:

Given the following strand of DNA, list he sequence of bases that would appear in the matching mRNA. For the under-

The graph

lined triplets, underline the corresponding

CGC TACAAGTCAGGTACCGTAACG

mRNA: \nticodons:

energy change

an endergonic or exer-

gonic reaction? 3.S.

II

the protein-coding portion of a piece of edited

mRNA

is

450 nucleotides long, how many amino acids will he in the corresponding polypeptide? (Hint: The start codon is translated into an amino acid but the stop codon is not.)

E> CD

c

CD CD CD

Time 121

CHAPTER

CELLULAR METABOLISM

4

Explorations Exploration 1: Animations of Metabolism Dynamic processes such as enzyme action or movement substrate through metabolic

from the

static

pathways

Explorations are

Christine Schmidt and her tissue engineering research, go to www.bme.utexas.edu/faculty/schmidt.

of

are difficult to visualize

when they show

drawings in a textbook, even

Exploration

you can find many animations on some of them created by students. An excellent animated primer on DNA and genetics that includes the details of DNA replication, transcription, and translation can be found

no

tion in Fig. 4-32). However,

still

the web,

American for

is

Google search

a

One

site

News

the educated layperson.

Physiological

in

by the American Physiological NIPS

Sciences

Society,

pub-

over a year old can be ac-

articles

Some

articles related to topics in this

that contains these

"Death to sperm mitochondria

NetBioChem {www.mcphu.edu/ netbiochem/NetWelco.htm). Under the TOPICS button, select GRAPHICS to look at the animations on enzymology and more

and

or article. Scientific

cessed free at www.nips.org.

(www.google.com) using the search terms activation energy ani-

mation or enzyme animation.

book

is

a periodical that publishes scientific review articles

lishes review articles.

some animations on enzymes, do

animations

Readings on Metabolism

substitute for a well-written

(NIPS), published

at www.dnaftb.org.

see

3:

Although you can find information on the Internet, there

the steps in sequence (for example, the drawings of transcrip-

To

also available at www.physiologyplace.com

is

mitochondrial

DNA

chapter include:

—A ubiquitin clue to why

comes only from Mom,"

Scientific

American, March 1999.

"The

bioenergetics.

the deep, the long/designer

tall,

genomes

—extreme

engineering," Scientific American, Winter 1999.

Exploration

2:

Biomedical Engineering

Biomedical engineering (BME)

is

a rapidly

"The

growing

field

with

cellular

Scientific

chamber

doom — A

of

look at proteasomes,"

American, January 2001.

researchers in almost every level of physiology, from tiny

nanomachines

home

to

artificial

hearts

(nano =

1

"A nonconventional role of molecular chaperones:

x 10~ 9 ). The

volvement

page for the Whitaker Foundation (www.whitaker.org)

has more information about the

"BME

ing (see

(®

A

field of

Sciences 16:123-126,

biomedical engineer-

"The

Glance") as well as a news archive that

presents exciting developments. To learn

more about

human

in Physiological

June 2001.

proteomics

nology 19(5):178-181,

Dr.

News

in the cytoarchitecture,"

In-

initiative (HPI)," Trends in Biotech-

May

2001.

ANSWERS Page 85 1.

7.

Amino

indicates that energy

being released, so this

ami nucleotides always con-

acids

The foaming-up

is

tion. The relatively large

tain nitrogen.

an exergonk

amount

oi

ised indicates that the reaction

Page 88

is

Page 96

reac11.

energy is

Modulators ma\

not

body

in the

is

energy

in

motion: sunn

is

Page 92 h.

ntropy

the substMtes air (peptidase),

state

ol

randomness

9.

in

Page 90 Uons

peptides

and

sucrose

["he rea< tants are is

i

baking soda and

arbon dioxide.

model, both reactants products

site.

Ill

can

4(c)

1,

5

es,

14.

amount

ot

enzyme

present decreas-

the reaction rate de< teases

an enzyme has reached saturation, the

li

prodw

Page

the loik-andkc\

15.

iic is at its

maximum.

Inegar;

in.

Bj

«>«>

(a)

.'>.

is

dephos-

membrane

Three types of post-translational modifica-

and

cross-linking.

sepa-

intermembrane

34.

Hemoglobin

with

four

subunits

is

a

to Figttr action rate ol 2.5

Fig. 4-c>:

tration

The graph shows an endergonk

rea»

is


s.

/ spanning protein

/

-S|EJf Cytoskeleton

"

protein

Intracellular fluid

128

Peripheral protein anchors the cytoskeleton to the cell

membrane.

>

\\

^k \s

^

Figure 5-4

«m hored

I

In

to the




Fig. 1-4, p. 7|.

and

(1)

we think

we can

together as a single unit,

compartments:

If

of

the cells of the body

all

body into two main

divide the

the intracellular fluid (ICF) within the cells

the extracellular fluid (ECF) outside the

(2)

partments are separated by the barrier of the

The

cells.

These com-

membrane.

cell

extracellular fluid can be further subdivided. The di-

viding "wall" in this case

is

the tissue wall of the circulatory

system. Plasma, the fluid portion of the blood,

lies

within the

circulatory system and forms one extracellular compartment.

The

system and directly

fluid that lies outside the circulatory

bathes the

cells

stare, to stand].

is

known

as interstitial fluid [inter-,

Figure 5-13

•

between +

shows the relationships between

Intracellular fluid

Interstitial fluid

these compartments. In

many

parts of the circulatory system,

tween the plasma and the

interstitial fluid

is

no exchange

possible

be-

Leaky epithelium

due to the ECF

thick walls of the blood vessels. However, in the smallest blood

made

vessels, called capillaries, the walls are

of leaky exchange ep-

Cell

The ithelium. The capillary walls act like a sieve, retaining blood cells

and

large proteins but allowing the

cross freely through spaces

remainder of the plasma to

between the

Although many materials move

and the

interstitial fluid,

extracellular

cells

freely

[

B

compartments

is

restricted

by the

compartment (ECF) is subdivided into plasma and interstitial fluid. Material moving between cells and ECF must cross the cell membrane. extracellular fluid

membrane

Fig. 3- 18a, p. 69].

between the blood

exchange between the

ICF

intracellular cell

and

membrane.

Figure 5-1 3

tom

Body

fluid

compartments

The box

half schematically illustrates the relationships

in the bot-

between

the compartments.

133

MEMBRANE DYNAMICS

CHAPTER

5

Whether

or not a substance enters a cell

ties

of the

stand

cell

how

membrane and

depends on the proper-

of the substance

classifies

can be selective about the materials that enter

cells

them, we must look in

the high-energy phosphate ine

of

^ MOVEMENT ACROSS MEMBRANES Some

molecules, such as water, oxygen, carbon dioxide, and

lipids,

move

easily across cell

ions, larger polar molecules,

Membrane

permeability

and very

more

proteins, enter cells with

is

membranes: the

bility or polarity

not enter

and can be changed by

[

p. 28].

I

size of

the molecule and

cell

membrane

move

off other

molecules

we examand out

move from one

mem-

place to another,

molecules or off the sides of a container. out concentrated in one area of an en-

start

them

to spread out gradually

throughout the available space.

known as diffusion. Diffusion may be defined as

This process

is

the

movement

of molecules

from an area of higher concentration of the molecule to an area

proteins are the mediators that

of lower concentration of the molecule.*

If

you leave

a bottle of

use to transport molecules across their membranes.

There are two ways to categorize

how

molecules

move

term diffusion to mean any random movement of They call molecular movement along a concentration gradient diffusion. To simplify matters, we will use the term diffiision to mean

*Some

across

texts use the

molecules.

membranes. One scheme describes movement according whether

it

to

net

movement

takes place through the phospholipid bilayer or with

down

of molecules

a concentration gradient.

1

'

i

Requires no energy other than that of molecular motion

Requires energy

ATP

from J

Diffusion

Endocytosis i

1

Simple

Facilitated

diffusion

diffusion

creates

Secondary

concentration

active

Exocytosis

Primary active

Phagocytosis

gradient

transport

for

transport

1 ,

.

Molecule

Mediated transport

goes through

requires a

membrane

lipid bilayer

.

Uses a membrane-bound vesicle

protein

I

PHYSICAL REQUIREMENTS

Figure 5-14

Map

of the

ways molecules nunc

at

mw

cell

membranes

Movement

ol

substances across

be lassifled bj the energj requirements ol transport (top part ol map) oi according to whether transport uses diffusion, a membrane protein, oi a vesl< le (bottom part ol map).

cell

154

into

molecules are constantly in motion. Gas molecules and mole-

until they are evenly distributed

has a specific mechanism for transporting

across. Usually,

requirements.

of ATP. In this section

closed space, their motion causes

lipid-solu-

cell

scheme

cells.

When

bilayer. Larger or less

from crossing the

bond

cules in solution constantly

alter-

Very small or lipid-soluble substances

lipid-soluble molecules are excluded

brane unless a

All

at all.

movement

its

energy

its

the different ways that substances

all

bouncing its

different

of Molecular Movement

membrane.

can cross directly through the phospholipid

cells

may

A

Diffusion Uses Only the Energy

the other hand,

properties of a molecule will influence

across cell

them

On

large molecules, such as

difficulty or

variable

ing the proteins or lipids of the

Two

membranes.

).

port requires the input of energy from another source, such as

membranes.

cules cross

5-14

Passive transport does not require input of energy. Active trans-

mechanisms by which mole-

detail at the

membrane protein (Fig. movement according to

the aid of a

To under-

itself.

membranes an i

i

Movement cologne open and

room,

later notice its fragrance across the

from where they are more concentrated

Diffusion has the following seven properties:

1.

Diffusion

creases

a passive process. Diffusion does not require the

is

input of energy from another source, such as the energy

sessed by

all

Molecules

move from an

10.

A

called a

is

say that molecules diffuse

rate of diffusion

centration gradient.

concentration gra-

down

ammonia, the

5-15 •).

(Fig.

depends on the magnitude

The

from

the gradient,

rate of diffusion

is

is

3.

a

evenly

libra,

ual molecules are

still

the

dynamic \dynamis,

system,

balance]

moving

molecule that exits one

how

power]

and

and the

equilibrium

state

much

slower

distances. Albert F.instein studied the' diffusion of

mechanisms

long

molecules

that

is

100 u.m for

Diffusion

is

To overcome the lim-

organisms have developed

that speed

up the movement

oxygen and nutrients rapidly

at

which they enter the body

directly related to temperature.

molecules

move

to the cells.

At higher tempera-

Because diffusion

faster.

significantly affect diffusion in

ova

it

starve to death.

occurs

diffusion

rate,

Most multicellular organisms have some form

is

a result of

changes

temperature do not

in

humans because we maintain

a relatively constant body temperature. 6.

Diffusion

ecule

is,

showed

is

inversely related to

the

more slowly

molecukn it

will

size.

The

larger a

Albert

diffuse.

that friction between the surface of a particle

medium through which movement. He

rapid over short distances hut

would

rate of diffusion. Generally,

but for each

in

At that

molecular movement, as temperature increases so does the

is

another one enters. The

equilibrium

cells

from the point 5.

diffusion stops. Individ-

at equilibrium,

area,

cell

would take years

capillary.

them-

distributed

system. Diffusion

to 2, diffusion takes

of circulatory system to bring

the

that the concentration has equalized throughout the

is

1

from the nearest

tures,

Once the molecules have

through

[aequus, equal +

4.

for diffusion in-

seconds to diffuse from the blood to a

of molecules.

air.

There will be net movement of molecules until the concentration

means

needed

.

times as long?

various transport

concentration gradient.

equal everywhere. selves

to 2, the time

1

the dis-

2

itations of diffusion over distance,

as the

dropped to zero because there

rate of diffusion has

no longer

to 2

the distance doubles from

toe,

when you open

most rapid

ammonia molecules first escape from the bottle into the Later, when the ammonia has spread evenly throughout room, the

l

if

nutrients to diffuse from the small intestine to cells in the big

of the con-

larger the concentration difference,

the faster diffusion takes place. For example, a bottle of

2

from

to B. In other words,

What does the slow rate of diffusion over long distances mean for biological systems? In humans, nutrients take five

difference in the concentration of a

higher concentration to lower concentration

The

If

many

area of higher concentration to an area of

substance between two places

We

A

proportional to the

is

molecules.

lower concentration.

dient.

to point B

CONCEPT CHECK

stored in ATP. Diffusion uses only the kinetic energy pos-

2.

A

square of the distance from

tance doubles from

they are less concentrated (across the room).

Membranes

that the time required for a molecule

from point

to diffuse

where

(in the bottle) to

and found

in solution

it is

because the aromatic molecules in the cologne have diffused

Across

it

diffuses

is

mol-

Einstein

and the

a source of resistance to

calculated that diffusion

is

inversely propor-

tional to the radius of the molecule: the larger the molecule,

the slower

its

diffusion through a given

medium.

A crystal of dye, such as potassium permanDiffusion placed in a beaker of water. \s tin crystal dissolves, dye mole-

Figure 5-15 ganate,

is

cules spread

outward by diffusion.

c Diffusion of dye molecules their

down

concentration gradient

Equilibrium occurs when is uniform

the concentration

135

CHAPTER

7.

MEMBRANE DYNAMICS

5

an open system or

Diffusion can take place in

that separates two systems. Diffusion of

within a room

across a partition

ammonia

or cologne

an example of diffusion taking place in an

is

open system. There

no

are

barriers to

and the molecules spread out

to

sion can take place between

two

fill

molecular movement,

the entire system. Diffu-

different systems, such as

the intracellular and extracellular compartments, but only the partition dividing the two compartments allows the

if

summary, diffusion

In

down

movement of molecules due to random molecular

the passive

their concentration gradient

movement. Diffusion large molecules.

cule

is

is

slower over long distances and slower for

is

When

the concentration of the diffusing mole-

come to equirandom movement of

equal throughout the system, the system has

librium and diffusion stops, although the

molecules continues.

dif-

fusing molecules to cross.

For example,

if

you

close the top of

an open bottle of am-

monia, diffusion cannot spread molecules into the room because the bottle

is

not permeable to the ammonia. However,

you cover the open mouth

keeper" plastic bag with tiny holes in smell the to the

ammonia

ammonia.

a molecule, that sion.

If

the

in the

Similarly,

it,

you

is

begin to

will

room because the bag is permeable if a cell membrane is permeable to

molecule can enter or leave the

membrane

cross. Table 5-2

if

of the bottle with a "vegetable-

cell

by

diffu-

not permeable, the molecule cannot

summarizes these points.

Lipophilic Molecules Can Diffuse Through the Phospholipid Bilayer The

membranes

ability of cell

hydrophobic

their

body, and solve in

and

to act as barriers

Water

is

a direct result of

the primary solvent of the

is

vital nutrients, ions,

because of

it

drophilic

many

lipid core.

and other molecules

dis-

polar nature. But substances that are hy-

its

dissolve in water are lipophobic as a rule: they

not readily dissolve in

do

For this reason, the lipid layer be-

lipids.

tween the cytoplasm and the

cell's

exterior acts as a

boundary

that prevents hydrophilic molecules from crossing.

Substances that can pass through the lipid center of the

membrane move by

diffusion. Diffusion directly across the phos-

pholipid bilayer of a

Table 5-2: Rules for Simple Diffusion

cell

membrane

is

called

simple diffusion and

has the following properties in addition to the properties of diffu1.

Diffusion

is

an uses only the kinetic energy of

a passive process that does not require

outside energy source.

It

molecular movement. 2.

3.

4.

sion listed

1.

The

molecules that are lipid-soluble (lipophilic) can traverse the

Diffusion

is

rapid over short distances but

much

central lipid core of the steroids,

Diffusion

is

Diffusion

is

molecule

is,

membrane by

slower over

move

faster

and diffusion

is

more

inversely related to molecular size.

the slower

across the

it

The

years,

it

was thought it

from

moving through the lipid center of the bilayer, but experiments done with artificial membranes have shown that the

larger a

will diffuse.

small size of the water molecule allows

through the

tent are less

to slip

between the

readily water passes

depends on the composition of the Membranes with high cholesterol con-

lipid layer

phospholipid

membrane

it

many membranes. How

lipid tails in

that separates two systems.

bilayer.

permeable to water than those with low choles-

rate of diffusion

The rate of diffusion through a the suri.K e area, the

membrane

.irc.i

more mole(

ol the

is

terol content, till

I

he

the spaces between the Eatty acid

the kidncv are essentially cells insert special

largei

ules can diffuse across per

.i

I

membrane, the slower

diffusion will take pla
.

a

membrane

membrane,

Ibis

is

in othei

more molecules can

e

time

136

move

lipids,

simple diffusion.

that the polar nature of the water molecule prevented

through a cell membrane depends on the ability oi the molecule to dissolve in the lipid layer of the membrane. Only lipid-soluble (lipophilic) molecules can (lilluse across the membrane by simple diffusion.

the

only

a rule,

lipophilic molecules can

some phospholipid membranes. For

directly related to temperature. At higher

Diffusion can take place in an open system or across a

The

and small

membrane. As

Water, although a polar molecule, can diffuse across

proportional to the surface

io.

so-

There will be net movement of molecules until the concentration is equal. Molecular movement continues, however, so this is called a dynamic equilibrium.

Diffusion across a

9.

to dis-

the membrane's phospholipid bilayer, but only nonpolar

partition

8.

of the molecule

ability

of the membrane. Most molecules in

lution can mingle with the polar phosphate-glycerol heads of

rapid.

7.

of diffusion depends on the

difference, the faster diffusion takes place.

temperatures, molecules

6.

rate

solve in the lipid layer

Molecules diffuse from an area of higher concentration to an area of lower concentration. The larger the concentration

long distances. 5.

earlier.

max seem obvious, but

it

directly proportional to

words, the larger the

diffuse across per unit

has Important imphca-

.

Movement tions in physiology.

One

striking

surface area affects diffusion

As lung tissue fusion of

move

oxygen decreases. Consequently,

is

rate

change

in

oxygen can

less

oxygen that reaches

not enough to sustain any muscular activity and

the patient

The

a

emphysema.

destroyed, the surface area available for dif-

into the body. In severe cases, the

the cells

3.

is

example of how

the lung disease

is

is

how

in the lipid

of diffusion across a membrane

is

alter

membranes tails and

pack themselves into the spaces between the fatty acids retard passage of molecules illustrates

through those spaces

Lipophobic molecules cannot enter a sion, therefore cells

(see Fig. 5-2).

the principles of Fick's law.

must make

cell

by simple

diffu-

special provisions for their trans-

the slower diffusion will take place. This factor comes into

port.

play in certain lung conditions in which the exchange ep-

membranes through protein carriers. Ions also cross membranes through open water-filled channels. However, the movement of

ithelium of the lung

thickened with scar

is

diffusion so that the

This slows

tissue.

oxygen entering the body

is

not ade-

quate to meet metabolic needs.

Smaller

lipophobic

ions through channels

and

molecules

ions

as concentration gradients. This

rules for simple diffusion across

rized in Table 5-2.

equation

known

membranes

are

summa-

They can be combined mathematically into an law of diffusion.

as Fick's

In

an abbreviated

form, Fick's law says that: Rate of diffusion

is

it

meansjhat ion

iTi

oygjnenljjjiot

particles

by way of membrane

Fick's law.

We

in the last sections of this chapter.

such as bacteria are too large to be

transported by protein carriers. They must

move

into

and out of

vesicles.

CHECK

x concentration gradient

membrane x membrane thickness

membrane

is

1 1

the most complex of the four

has several factors that influence

it:

(

1 )

1

(2)

2.

Where does Which

is

Answers:

the energy for diffusion

more

likely

to cross a

cell

p.

169

come from?

membrane by

simple

diffusion: a fatty acid or glucose?

the size of 1

the diffusing molecule,

cell

proportional to

resistance of

terms because

movement

Macromolecules and

cells

available surface area

resistance of the

will discuss ion

cross

influenced by electric gradients as well

is

simple diffusion and cannot be predicted by using

The

The

may

between the individual

slip

phospholipids. For example, cholesterol molecules in

inversely proportional

of the membrane. The thicker the membrane,

can

Membranes

to diffusion decreases.

composition of the membrane

easily diffusing molecules

Figure 5-16

confined to bed.

to the thickness

Changes

membrane

resistance of the

increases,

Across

the lipid-solubility of the molecule,

3.

What happens

to the rate of diffusion

in

each of the

following cases?

and

(3)

the composition of the lipid layer across which

it

is

dif-

(a)

membrane

to

(b)

concentration gradient increases

diffusion increases. As lipid solubility of the diffusing molecule

(c)

surface area decreases

fusing. As molecular size increases, resistance of the

membrane

thickness increases

(continues

on next page)

Extracellular fluid

Membrane

Concentration outside cell

Molecular

Lipid

surface area

^size

solubility

i

Factors affecting rate of diffusion through a cell membrane: • Lipid solubility •

Membrane

Molecular size

• Cell

thickness

Composition

Concentration

of lipid layer

gradient

membrane

thickness

•

Concentration gradient Membrane surface area

•

Composition

•

of lipid layer

Concentration

Intracellular fluid

inside cell

Fick's

Law

Membrane

of Diffusion says:

available surface area • concentration gradient

Rate of diffusion

membrane

resistance

•

thickness of

membrane

resistance

lipid solubility

Membrane

resistance

•

molecular size

Changing the composition of the lipid layer can increase or decrease membrane resistance.

Figure 5-16

law of diffusion simple diffusion across a membMiie. Fick's

Fick's

law of diffusion mathematically relates factors that influence the rate of

137

CHAPTER 14.

MEMBRANE DYNAMICS

5

Two compartments

are separated by a

membrane

that

Both passive and active forms of mediated transport demon-

is

permeable only to water and yellow dye molecules.

strate three properties: specificity, competition,

Compartment A is filled with a solution of yellow compartment B is filled with a solution of equal

These concepts were introduced in the discussion on enzymes

concentration of blue dye.

the system

If

what color will compartment A (Remember, yellow + blue makes

for a long period of time,

yellow, blue, or green?

[i* p. 97].

undisturbed

left

is

dye,

and

saturation.

Mediated transport shares these properties with en-

zymes because both processes depend on the interaction of a sub-

be:

strate

with a protein.

green.)

Specificity 15.

What keeps atmospheric oxygen from diffusing into our bodies across our skin? (Hint: What kind of epithelium is

Specificity refers to the ability of a carrier to

move only one molecule or a group of closely related molecules. One example of specificity is the family of transporters known as the GLUT transporters. These membrane proteins move six-

skin?)

carbon sugars

Carrier-Mediated Transport Exhibits Saturation, Specificity, and Competition Movement

membranes with the aid of a mediated transport. Some mediated

of substances across cell

transport

known as carriers move only one

known

uniport

carrier protein

as

carriers that

is

move two

protein that

is

called a cotransporter.

direction,

symport

moves more than one kind If

together +

of molecule at

the molecules are

whether into or out of the [sym-,

cell,

moving

shown If

+

portare, to carry].

If

is

and

if

concentrations are equal inside the

substance against

known

called

the molecules are is

called antiport

are

and moves molecules down

passive

as facilitated diffusion.

ATP its

If

p. 35],

across cell

membranes. But

will

not transport the disaccharide maltose or

that

is

net transport stops

cell

and

when

out, the process

protein-mediated transport

or another outside source

concentration

gradient,

is

re-

and moves

the

process

a is

Competition specificity.

A

Competition

Uniport carriers

transport only

GLUT

a property closely related to

is

may move

transporter

several

group of substrates, but those substrates other for the binding the

GLUT

sites

move

transporters

members

will

on the transport

of a related

compete with each

proteins. For example,

the family of hexose sugars, but

GLUT transporter has a "preference" for one or more hexoses, based on its binding affinity. The results of an experiment demonstrating competition are

each different

in Figure 5-18

transporters are

moving

the arrow, glucose transporters have

is

.

In the initial part of this graph,

added to the extracellular

galactose

is

fluid.

Because the

a higher binding affinity for glucose than for

galactose, glucose replaces galactose

When

one

displaced from

rate of galactose transport into the

kind of substrate.

Symport carriers move two or more substrates in the same (b)

direction across the

membrane. Types of carrier-mediated transport

GLUT

galactose into a cell at a constant rate. At

on some of the binding

some cell

of the transporters, the

Antiport carriers substrates in opposite directions.

(c)

move

sites.

decreases. In this example,

Glucose

138

form of glucose

monosaccharides.

Cotransporters

Figure 5-17

a

not normally found in nature. Thus we can say that

glucose and galactose are competing for the transporter.

as active transport.

(a)

GLUT transporters

transporters are specific for the naturally occurring six-carbon

shown

their concentration gradient,

quires energy from

is

same

c.

mediated transport

known

one time

Symport and antiport

to carry].

portare,

in Figure 5-1 7b,

to find

in the

the process

being carried in different directions, the process [and, opposite

common

it is

or even three different kinds of molecules.

A

[

such as glucose, mannose, galactose, and

kind of molecule, a process

5-17aO). However,

(Fig.

fructose

(hexoses),

Movement

M

E

*r,The

GRAPH QUESTIONS Why does

•

Draw a

galactose transport decrease when glucose is added? line that

GLUT Transporter

found

diffusion

glucose transport.

o a w c

some yet

Glucose added T

CO

in

every

of the body. For

cell

It

a> co

was

o

other

was not

cells,

until

identified.

O)

cells,

many

years, scientists

different variants of the carrier. In

was independent

it

the

1

980s that the

To date,

isolated.

o

hexose sugars are

for the

glucose transport was regulated by hormones,

cells,

in

Family

carriers

assumed that there were

represents

Membranes

C

E R

Facilitated •

Across

The

first

six

hormonal

of

first

glucose transporters have been

from red blood

transporter, isolated

was named GLUT1

.

action.

glucose transporter

This protein

the facilitated

is

dif-

"o

moves glucose and other hexoses

fusion carrier that

a>

most

DC

Time

cells of

the body. The

the hepatocytes of the

brane of transporting

Glucose and galactose use the same membrane transporter. The transporter has a higher affinity for glucose than for galactose.

testine.

CLUT3

and muscle.

hormone Sometimes the competing molecule merely blot

ks the transport

i

not transported but

is

another substrate

,

in this case,

and

is

It

is

insulin.

transporter

is

a competitive inhibi tor

[

»* p.

cose transport system, the disaccharide maltose (Fig.

5-19

).

once bound,

competes with glucose

It

too large to be

is

moved

95] is

across the

in

medicine. For example, gout

evated uric acid in the plasma. uric acid

is

to

enhance

its

is

One method

ol

kidney and

in

in-

into

adipose tissue

GLUT5

is

actually a fructose transporter

the transporter present on the apical

membrane

of

The protein named GLUT6

cells.

turned out not to be a transporter, but by the time that

an inhibitor site,

was discovered, GLUT7 had already been named. GLUT7

but,

is

membrane.

a disease

mem-

and other hexoses found

in

the glucose transporter regulated by the

the

Competition between transported substrates has been put

good use

found

In the glu-

.

binding

for the

is

is

basolateral

epithelial cells in the

the intestinal epithelial

competing molecule

transporter

and on the

liver

transports glucose

GLUT4

neurons. The

Graph of competition

Figure 5-18

CLUT2

into

caused by

an

intracellular transporter

reticulum

to

membrane. The

found on the endoplasmic

restriction

transporters to different tissues

el-

is

of different

GLUT

an important feature

in

the metabolism and homeostasis of glucose.

decreasing plasma

excretion in the urine. Normally, the

kidney's organic acid transporter reclaims uric acid from the urine.

However,

if

tered, the carrier

an organic acid called probenecid

venting the reabsorption leaves the in

body

is

Saturation

adminis-

ol uric

at id.

As

a result,

more

uric

acid

just as

rate of substrate transport

the rate of

enzyme

substrate concentration

in the urine, lowering the uric acid concentration

«» [

activity p. 96).

number

depends on both

of carrier molecules,

depends on both enzyme and For a fixed

number

of carriers,

however, as substrate concentration increases, the rate increases

the plasma.

Extracellular fluid

CZT

The

the substrate concentration and the

binds to probenecid instead of to uric acid, pre-

or

Glucose

Glucose Maltose

GLUT transporter Intracellular fluid

(a)

The

across

GLUT transporter cell

membranes.

brings glucose

(b)

Maltose

a competitive binds to the GLUT

is

inhibitor that

transporter but

is

carried across the

not

itself

membrane.

Figure 5-19

Competitive inhibition 139

CHAPTER

MEMBRANE DYNAMICS

5

II of energy. Active transport requires energy input from ATP, either directly or indirectly.

GRAPH QUESTION

CHECK

On

the x-axis, mark the substrate concentration at which the carriers first

become

1

What would you

6.

Answers:

call a carrier

1

substrates

a cell

might increase

its

69

in

way

Using the door analogy above, can you think of another

7.

1

membrane?

opposite directions across the

saturated.

moves two

that

p.

maximum

transport rate?

Facilitated Diffusion Is Diffusion That Uses Membrane Proteins Some

polar molecules appear to

move

though we know from

diffusion, even

into and out of cells by

chemical properties

their

that they are unable to pass easily through the lipid core of the Extracellular substrate concentration

membrane. Most of these polar molecules travel by facilitated diffusion, in which carrier proteins transport them across the cell membrane. Glucose and amino acids are examples of cell

Transport rate is proportional to substrate concentration until the carriers are saturated.

Graph showing saturation of carrier-mediated

Figure 5-20

molecules that enter or leave diffusion carriers.

transport

same properties

Facilitated diffusion has the

up

to a

maximum,

the point at which

all

carriers are filled

substrate. At this point, the carriers are said to

working

ration. At saturation the carriers are rate,

no

and

have reached satuat their

shows saturation represented

5-20

effect. Figure

with

maximum

concentration will have

a further increase in substrate

The molecules move down

sion.

no input

process requires

when

equilibrium,

door has a

maximum number

concentration inside the

of people that

it

can

all

the

[glucose] ECI

.

=

maximum of 100 people per minute to enter the hall. This is the maximum transport rate, also called the transport maximum. When the concert hall is empty, three maintenance people enter the doors every hour. The transport

phosphate, the

doors together can allow a

the

3 people/60 minutes, or 0.05 people/minute, well under

maximum.

For the local dance

minute go through the doors,

when

still

recital,

about 50 people per

well under the

maximum.

When

sands of people are clamoring to get allow 100 people/minute into the

maximum

rate,

so

3000 people trying

it

in.

hall.

How

can

cells

the doors open, thou-

They are working

The transport

rate

is

withdraw

insert additional carriers

membranes. Under other circumstances, carriers to decrease

movement

a cell

may

of a molecule Into or out

as glucose enters the cell,

cell

lorms

oi

mediated transport show saturation,

and competition. But they transport, better

known

clilter in

othei ways

With

|*

by keeping the concen-

glucose, for example, this

first

it is

(Fig.

5-22 •). As

phosphorylated to glucose

step of glycolysis

[

6-

103]. Addition of the

»* p.

low and also prevents glucose from leaving the

CHECK 1

8. Liver cells

p.

169

and make

glucose concentrations higher than the

extracellular glucose concentration.

happens to

cell.

Answers,

are able to convert glycogen to glucose

intracellular

facilitated diffusion of

What do you think when this occurs?

glucose

Active Transport Requires the Input

of Energy from \ctive transport

spe


is

hyperosmotic to A

C

is

isosmotk

B

is

hyperosmotic to

C

C

is

hyposmotic

1

OsM NaCL

to B

153

CHAPTER

MEMBRANE DYNAMICS

5

RUNNING PROS

Table 5-7: Tonicity of Solutions

Daniel's medical history

stant medical

problems since

ratory infections,

months,

tells a

frightening story of almost conbirth: recurring

weight

loss.

began having trouble breathing, hospital.

A

his

Daniel

mother rushed him

to the

last

and dehydrated.

mucus from

his

breeding

In cystic fibrosis, this thick

ground

thickened mucus

of the epithelial cells

Question 3:

infection-causing

for

in

and

Why would

THE SOLUTION

SOLUTION

IN

A

Cell swells

Solution

A

is

hypotonic

Cell doesn't

Solution B

is

isotonic

C

is

hypertonic

B

change

size

caus-

Solution

Cell shrinks

a per-

bacteria. The CFTR channels.

lutions (solution

tion 2

the lungs transport chloride ions out

a

is

into the airways.

hyperosmotic to solution

is

1

comparative term for a

happen

to cell

volume

1).

Tonicity,

were placed in the solution. For ex-

a cell

if

therefore solu-

2,

on the other hand, solution that describes what would

hyposmotic to solution

is

failure to transport chloride ions into

the lumen of the airways cause the secreted

Remember

mucus

and provides

a direct result of faulty

is

Normal CFTR channels

(Hint:

week,

airways was unusually

es life-threatening respiratory congestion fect

six

when

Then,

DESCRIPTION OF THE SOLUTION RELATIVE TO THE CELL

WHEN PLACED

culture taken from Daniel's lungs raised a red flag

for cystic fibrosis: the

thick

and, for the past

digestive ailments,

a history of

CELL BEHAVIOR

bouts with respi-

mucus

to

ample, "Solution

be thick?

hypotonic to red blood

1 is

red blood cells would swell at equilibrium

that water moves to dilute the more concen-

in solution

Tonicity has

1.

no

The

units.

you that

cells" tells

the cells were placed

if

tonicity of a solution

is

trated region.)

characterized relative to a particular

Q ^ ^ £j© ^

Furthermore, the tonicity of a solution depends not only on its

solution. Osmolarity says

nothing about what the

particles are

and how they behave. Before we can predict whether osmosis must know the properties of the membrane and of the

cross the cell

we on

can enter the

solutes

membrane is move by osmosis from a less concentrated (hyposmotic) solution into a more concentrated (hyperosmotic) solution, as illustrated in Figure 5-34. This movement follows the saying "water moves to dilute the more concentrated solution."

NaCl.

Most biological systems

of water

solutes, water will

membranes

are not this simple, however. Biological

are selectively permeable

cross in addition to water.

and out of

cells,

and allow some

solutes to

you must know the

tonicity of

the solution, ex-

If

a cell

is

may

a physiological term,

what would happen

to cell

if

solution [tonikos, pertaining to stretching].

If

were placed

a cell gains water

and

when placed in a solution and allowed to come to equilibrithe cell um, we say that the solution is hypotonic to the cell. loses water and shrinks when placed in the solution, the solution said to be hypertonic. is

It

the

cell

does not change

ways describe the tonicity of the solution Mow,

equilib-

we

tion.

number

oi particles in

,i

and NaCl

desc ribe a single solution (in osmoles/llter) or to

it

is

a

few

+

is

If

therefore con-

How

and

C'l

will

cannot enter the

cells.

cell in it? s

t

The key

lies in

knowing the

>iutcs in the cell

and

relative concentrations

in the solution.

By conven-

that cells are filled with nonpenetrating

compare two

so-

membrane remains

unable to

and

in the cell.

cell.

The

cell swells, ,u\d

the eell has a lowei

Here are the

//

rules.

com

The

the

cell

cell shrinks.

com

and

movement

the solution

is

ot w.itei

hypotonic.

movement

ami the solution

is

the solution, there I

he solution

is

is

no

net

out ot the

ot w.itei

hypertonh

entrations ot nonpenetrating solutes .»< the

equilibrium.

into

entration of nonpenetrating solutes than

the solution, there will he net

.•?.

you

the nil has a highei concentration at nonpenetrating solutes

the If

cell,

a

concentrations of nonpenetrating

than the solution, there will be net

2.

intact.

solution relative to

a

ol

relative

solutes in the solution If

a solu-

can you figure out the tonicity of the solution without

we always assume

cell.

can be used to

solution

a saline

put into the plasma, tin \a

To determine tonicity

relative to the cell.

solution,

+

by the Na -K -ATPase. NaCl

must consider the

al-

then, does tonicity differ from osmolality.' Osmolality

describes the

154

Size

isotonic (Table 5-7). By convention,

cell. (In reality,

Suppose you know the composition and osmolarity of

It

rium, the solution

into the

stay in the extracellular fluid because they

1.

is

ions

leave as long as the cell

swells

is

solute in physiolog\

sidered a functionally nonpenetrating solute.)

tion,

the

.it

solutes.

solutes. In other words, the solutes inside the cell are

in

a cell

call particles

Na +

extracellular fluid

used to describe solutions, that

volume

We

penetrating solute.

leak across, but they are immediately transported back to the

putting a

The Tonicity of a Solution Describes How the Size of a Cell Would Change If It Were Placed in the Solution tells

a

membrane nonpenetrating

placed in a solution of NaCl, the Na* and CI

of nonpenetrating

is

it

will

membrane

not cross the

To predict the movement of water into

plained in the next section.

Tonicity

call

The most important nonpenetrating

permeable only to water and not to any

the

we

cell,

that cannot cross the cell

each side of the membrane. If

on the nature of the solutes in the solution. By we mean whether the solute particles can membrane. If the solute particle (ion or molecule)

osmolarity, but

nature of the solutes,

will

take place between any two solutions divided by a membrane,

cell.

movement

isotonh to the cell.

same ot

in the

water

at

•

The

starting osmolalities of the cell

that penetrating solutes,

which contribute

when determining

be ignored

One

the

the

membrane

cell

placed in a

look

true,

move

freely into

why

5-35a«, the

In Figure

trating solute in

1

liter

of volume.

tains 6 particles of solute per

liter:

The

1

3 nonpenetrating particles

i.e.,

are

Solution

®

J

and

and solution have the same

concentrations (6 particles per

they are isosmotic.

liter),

and solution have equal

concentrations, isosmotic.

of solution also con-

liter

3 penetrating particles. Because cell

To

(a)

Cell

contains 6 particles of nonpene-

cell

the Body

this

the following example.

at

in

did not exist, and therefore do

not contribute to the solution's tonicity. To understand is

Water and Solutes

must

is

a cell

solution with penetrating solutes, these solutes cell, as if

reason

to osmolarity,

When

tonicity.

Distribution of

and solution usually can-

not be used to determine the tonicity of the solution. is

The

(b)

compare the concen-

determine tonicity of the solution,

and

trations of nonpenetrating solutes in the solution

cell.

The

When

the

cell is

placed

in

the

no water moves initially because the cell and solution are in osmotic equilibrium. solution,

solution has 3 nonpenetrating particles per

nonpenetrating particles per

move from

that water will

liter.

liter,

By rule

the solution into the

movement

of water into the cell will increase

solution

hypotonic to the

is

isosmotic to the If

cell,

When

lies

the

has 6

its

cell.

The net

volume, so the

even though the solution was

the solution was isosmotic to the

solutes.

cell

before they were put together.

cell

The answer

sis?

but the

above, this means

1

what caused osmo-

cell,

with the gradient of the nonpenetrating

cell

was

placed in the solution, there was

first

no osmotic gradient (and no water movement) across the cell membrane because cell and solution both had concentrations of 6 particles per cal

liter

dig. 5-35b). However, there were chemi-

concentration gradients: the nonpenetrating solutes were

(c)

However, there

is

a concentration

gradient for the penetrating solute

@, which diffuses into the cell.

This

disrupts the osmotic equilibrium, so

water follows the solute into the

cell.

L

more concentrated in the cell (6 versus .{), while the penetrating solutes were more concentrated in the solution (3 versus 0). The nonpenetrating solutes could not cross the membrane, but the penetrating solutes were free to diffuse

and move into the

tration gradient

moved

in,

1

solute into the cell

ment has no

and the

tonicity. ties

is

he

I

cell

some

volume increased (solute moveon cell volume). Thus, in this ex-

is

clinical decisions

medicine, the tonicity of

portant consideration.

One purpose

into dehydrated cells (in

which

case,

at equilibrium, therefore

was

hypotonic.

which

about intravenous

a solution

of IV fluids

case, a

an isotonic solution

depends on how the

distribute

clinician

is

an im-

is

hypotonic solution

between the extracellular and

approximate osmolarity cell.

is

used).

FIGURE QUESTION

to get water is

The choice

of

Using the same

cell,

give the relative osmolarity

the following solutions,

if

the solution has

and the

tonicity of

6 nonpenetrating

(a)

6 nonpenetrating and 3 penetrating particles, or nonpenetrating and 6 penetrating particles. particles, (b)

(c)

3

wants the solutes and water to

partments. Table 5-9 shows the most

human

volume

and

used) or to keep fluid in the extracellular fluid to replace blood

their

,

the solution

hypotonic.

rules for dealing with osmolarity

making good

(IV) fluid therapy. In

fluid

Equilibrium is restored when the concentrations of nonpenetrating are equal in the cell solutes (|J and the solution. The cell gained

Understanding the difference between the two proper-

critical to

loss (in

(d)

parti-

1

cell

ample, an isosmotic solution lists

5-/55c).

gradient was created, water followed the

significant eftect

Table 5-8

concen-

while the solution had 6 -

particles,

Once an osmotic

their

As soon as one particle

an osmotic gradient was created dig.

contained 6 + cles.

cell.

down

intracellular fluid

common

com-

[V solutions

,wk\ tonicity relative to the

and

normal

Figure 5-35

Tonicity depends on the relative concentra-

tions of nonpenetrating solutes

®

can cross the nonpenetrating solutes

solutes

cell

^

Water and penetrating

membrane

cannot

but

cross.

155

CHAPTER

5

MEMBRANE DYNAMICS

CHECK

RUNNING PROB Three days

after Daniel's

sults: salt levels in his

tration.

Daniel

sweat

test,

re-

Which

27.

cystic fibrosis.

Now, along

mucus

loosen the

enzymes

in his

airways, Daniel

must begin

a

his

will

Why

will

Daniel starve

if

he does not take

(a)

1

(b)

1

M M

volume?

(c)

1

OsM

Compartment B

NaCI

1

OsM

urea

2

M

1

OsM

NaCI

who

29. You have a patient

lost

NaCI

urea urea

blood and you need to blood transfusion

of

liter

1

volume quickly while waiting arrive from the blood bank.

restore

© © © ©£i®

to

(a)

Would in

for a

be better to administer in water?

it

water or 0.9% NaCI

how

these solutes distribute

in

5%

dextrose (glucose)

(Hint:

Think about

the body.) Defend your

choice.

Table 5-8: Rules for Osmolarity and Tonicity (b)

By convention, we assume

unit

artificial

pancreatic enzymes?

1.

most water per NaCI?

OsM

1

Membrane

Compartment A

probably die before the age of 30.

Question 4:

NaCI, or

life.

mucus in the pancreatic ducts blocks the secretion of digestive enzymes into the intestine. Without artificial enzymes, he would starve. Yet even with these treatments, In cystic fibrosis, thick

Daniel

M

1

70

are separated by a membrane that is permeable to water and urea but not to NaCI. Which way will water move when the solutions below are placed in the two compartments?

regimen

to be taken whenever he eats, for the rest of

solution(s) has/have the

glucose,

1

Two compartments

28.

with antibiotics to prevent lung infections and therapy to

of

M

1

sweat are over twice the normal concen-

diagnosed with

is

the lab returns the grim

Answers: p.

How much

of

your solution of choice would you have volume to normal?

to administer to return blood all

intracellular solutes are

nonpenetrating.

When

2.

a cell

solutes will

is

exposed to a solution, water and penetrating the system will go to equilibrium. At

move and

equilibrium the total concentration of solute particles in the cell

and the solution

will

be the same.

we have

of a

cell

and a solution before they

many body

seen that the compartments of the body are in

solutes are ions that carry either positive or negative

be the same.

trical

tonicity of a solution

is

determined by the volume of the

equilibrium (see Table 5-7).

we must

also consider the distribution of elec-

charge between the intracellular and extracellular compart-

ments. Although the body as a whole a

matching positive ions are found

solution.

(Na

that

is

You cannot predict the tonicity of isosmotic and hyperosmotic solutions unless you know the concentration of nonpenetrating solutes relative to the cell. Net water movement will be into the compartment that has the higher

Potassium (K + )

+

electrically neutral,

)

is

the major cation of the

D

s

D5

— 0.9% saline W

anions of the intracellular

fluid.

cell that

0.45%

do not

Isosmoth

Isotonic

5%

dextrose** in normal saline

Hvperosinotk

Isotonic

5%

dextrose

Isosnu'tu

ii\

Half-normal saline

saline

D s—0.45% saline •Saline

156

n.i(

I

dextrose Dextrose

glucose.

In

half-normal saline

151).

do not have matching cations and

ions in the extracellular fluid that

Noriiuii saline

watei

and sodium

However, there are some protein

rONl( in

In

cells,

whereas phosphate ions and negatively charged proteins ate the

OSMOLARIT*

0.9%

saline*

KNOWN AS

has

in the extracellular fluid,

Table 5-9: Intravenous Solutions ALSO

it

while their

fluid (see Fig. 5-33, p.

Chloride ions (CP) remain with Na*

some K +

SOLUTION

fluid,

in the extracellular fluid.

dominates the extracellular

anions inside the

concentration of nonpenetrating solutes.

is

few excess negative ions in the intracellular

hyposmotic to a cell will always be hypotonic, no matter what the nature of the solutes in the

A solution

6.

far,

electrical charges,

cell at 5.

the osmolarities

are put together, because at equilibrium, the osmolarities will

The

4.

is,

of Electrical Disequilibrium Thus

osmotic equilibrium but in chemical disequilibrium. Because

Compare the osmolarity

3.

be equal; that

will

The Body Is in a State

1

1\

posmotic

Hyperosmotic

potonlc

Hypotonic Hypotonic

haw

matching

The

anions.

One consequence

is

commonly known

compartments

extracellular

The

electrical equilibrium.

uneven distribution of ions

of this

and

that the intracellular

are not

electrical disequilibrium in the

membrane

as the resting

is

in

body

potential difference.

from the separation of

tricity) arises

when

Distribution of

electrons

move from

Water and Solutes

Are Generated

Cells

The concept

tionally

been taught

of resting

membrane

the chapters

in

Many Types

in

of

charge that occurs

electrical

the amber atoms to the cloth. To sep-

arate these charged particles, energy (work)

must be put into the

system. In the case of the amber, work was done by rubbing the

work

rod. In the case of biological systems, the

Electrical Signals

the Body

in

is

done by

usually

energy stored in ATP and other chemical bonds.

potential has tradi-

on nerve and muscle func-

known

tion because those tissues generate electrical signals

as

action potentials. Yet one of the most exciting recent discoveries

Cell Membrane Allows Separation of Electrical Charge in the Body

The

In the body, separation of electrical charge takes place across the in

physiology

is

the realization that other kinds of

use

cells also

membrane. This process

cell

communication. This section reviews the

electrical signals for

basic principles of electricity

ing

membrane

and discusses what

The chapter ends with

potential.

tial

creates the rest-

a

look at

the

minus

They

composed

are

are electrically neutral

atom

is

known

as

important in the

an

We

ion.

human

of these positive ions,

in

balanced pro-

neither positive nor negative.

moval or addition of electrons particle

to

an atom creates

body

a

The

re-

charged

Na

body, such as

somewhere

there

+

K

,

is

a

+ ,

and

H

+ .

matching

For each electron,

when Na

in

enters in the form of NaCl, the "missing" electron from

+

Na can be found on The following

The

principles are important to

remember when

bilayer of the artificial

The law of conservation of

electric

charge

states that the

amount of electric charge produced in any process is zero. This means that, for everj positive charge on an ion, there is an electron on another ion. Overall, the human body

In the

2.

electrically neutral.

positive ions ent.

membrane. This

(

+ out of the )

The negative ions

try to

move

into the

to leak across

As soon as the

3.

and negative charges,

use energy. For example, energy

is

it

is

is

disrupted: the

impermeable to negative

is

cell.

cell,

needed to separate the

ward each ing

is

other, the material

called a

move

freely to-

through which they are mov-

conductor. Water

is

a

good conductor

of

move through the material that separates them, the material is known as an insulator. The phospholipid bilayer of the cell membrane is

electricity.

a

good

If

separated charges are unable to

insulator, as

is

the plastic coating

on

electricity

electrical wires.

comes from the Greek word

they rubbed a

elektron, for

The Greeks discovered that if rod of amber with doth, the amber acquired the

amber, the fossilized resin of

ability to attract hair

and

by the negative charge

membrane does not

positive ion leaves the

first

allow ions

cell,

the electrical

has a net charge of -1, while the

cell's interior

membrane

The input of energy

to trans-

has created an electrical gradient:

example, the inside of the

became negative

cell

relative to

active transport ot positive ions out of the cell also cre-

ates a concentration, or chemical, gradient: there are

ions outside the

electrical

chemical gradient. The cause water can

move

more

posi-

than inside. The combination of

cell

and concentration gradients cell

remains

in

freely across the

called

is

an electro-

osmotic equilibrium be-

membrane

movement. An electrical gradient between the

in

response to

solute

the intracellular fluid tial

difference or

name sounds The word

Positive ions outside the cell

attracted

exterior has a net charge of +1.

The tive

separated positive and negative charges can

ions, so

the outside.

necessary to

protons and electrons of an atom. 4. If

is

move

equilibrium between the extracellular fluid and intracellular fluid

in this

To separate positive

energy to

carrier uses

it.

port ions across the

protons and electrons in an atom exhibit this attraction.

at os-

(-) in the cell attempt to follow the posi-

they remain trapped within the

two charges of the same type + and + or - and -)

The

is

against their concentration gradi-

cell

membrane

Opposite charges (+ and -) are attracted to each other, but repel.

intracellu-

ions because of the attraction of positive and negative

tive

cell's

(

and

next step (Figure 5-36b), an active transport protein

inserted into the

net

is

extracellular

motic, chemical, and electrical equilibrium.

of the intracellular fluid, but the 1.

cell, like

not permeable to ions. Water can freely

ion concentrations equal. In Figure 5-36a, the system

might

dealing with electricity in physiological systems:

cell, is

membrane, making the

cross this cell lar

placed in a similar solution, also electri-

cell is

the bilayer of a real

charges. But the

the CI".

dia-

by the plus and

ions, represented

The phospholipid

cally neutral.

have discussed several ions that are

usually found as part of a negative ion. For example,

the

21].

of positively charged protons, negatively

charged electrons, and uncharged neutrons, but portions, so that an

p.

[

.

with molecules that dissociate

Because the molecules were electrically neutral to

signs.

inside the cell.

Atoms

» The

in Figure 5-36

begin with, there are equal numbers of positive and negative ions

to trigger insulin secretion.

Electricity review

artificial cell filled

and negative

into positive

how

membrane poten-

beta cells of the pancreas use changes in their

gram shows an

shown

is

is

known

membrane

intimidating,

extracellular fluid

as the resting

membrane

and

poten-

potential, for short. Although the

we can break

it

apart to see

what

it

means.

trees.

dust. This attraction (called static elec-

1.

The

resting part of

electrical gradient

the is

name comes from

seen in

all

the fact that this

living cells,

even those that 157

w

.

CHAPTER

MEMBRANE DYNAMICS

5

appear to be without

reached a steady state and

tential has 2.

The

electrical activity.

potential part of the

membrane

cell

gy.

When

a source of stored, or potential, energy, is

a

form of potential ener-

oppositely charged molecules

come back

together,

two

scales.

On

than an absolute

electrical gradients

scale. Figure

simple example has a charge of +1 from the positive ion charge of -1

gained, while the intracellular fluid has a

negative ion that was

measure the charges

we

behind. However, in

left

as

numbers

stead

sending

gives the intracellular fluid a charge of -2, the

The

difference part of

membrane

the

name

is

to

remind you that the

potential represents a difference in the electrical

charge inside and outside the

cell.

The word

difference

is

often

dropped.

(a) Cell

and solution are

electrically

and chemically

the

membrane

the

first.

at zero

artificially setsjone side

and measures the second

side relative to

In our example, resetting the extracellular fluid to zero cell's

resting

mem-

for measuring a cell's membrane poshown in Figure 5-37 I Electrodes are created from hollow glass tubes drawn to very fine points. These micropipets are filled with fluid that conducts electricity. They are con-

The

equipment

actual

tential difference

is

.

nected to a voltmeter that measures the electrical difference

cell.

A

reference electrode

which represents the

In living systems,

+

|0

A

in volts (V) or millivolts (mV).

membrane

inserted through the cell

is

plasm of the bath,

+

is

recording

into the cyto-

placed in the external fluid

extracellular fluid.

by convention, the extracellular fluid

When

mV.

recording electrode

the voltmeter

is

placed inside a living

cell,

the

measures the membrane potential (V m ), the electrical difference between the intracellular fluid and the extracellular fluid. A chart

+

membrane membrane

+

cells,

and solution in chemical and electrical disequilbrium. Energy to pump one cation out of the cell, leaving a net charge of -1 the cell and +1 outside the cell.

(b) Cell

used

mV). As you saw

On an

(c)

be

a recording of the

the voltmeter will record a resting

-40 and -90 mV,

potential difference between

cating that intracellular fluid lar fluid (0

make

potential difference versus time.

For nerve and muscle

is

indi-

negative relative to the extracellu-

in Figure 5-36c, the extracellular fluid

absolute charge scale, the extracellular and the intracellular fluid (ICF) at -1

fluid

(ECF) would

at +1

Extracellular fluid

Intracellular fluid

I

\ +

+

+2

+1

-1

+

Absolute charge scale

\

A©

+

T •

©

.0

f

©

//

© •

+

• © •

I

I -2

—

to the

158

Separation of ehi tin al liarge

left

+2

+1

-1

Relative charge scale

Physiological

i

Extracellular fluid

Intracellular fluid

extracellular fluid set to

measurements are always on a

(ground).

relative scale,

on which

assigned a value of zero. This shifts the scale and gives the inside of the cell a relative charge of -2.

the extracellular

Figure 5-36

is

designated as the ground and assigned a charge of

recorder connected to the voltmeter can

+

of

at equilibrium.

+

in

lost. In-

brane potential difference.

electrode

is

for the

use a device that measures the difference in electrical

between two points

i

it

we cannot

real life

of electrons gained or

charge between two points. This device

electrical signals.

a rela-

5-36c compares the

moving down their concentration gradient can perform work. The work done by electrical energy includes opening voltage-gated membrane channels and that molecules

on

the absolute scale, the extracellular fluid in our

they release energy that can be used to do work, in the same

way

3.

is

we measure

In living systems, tive scale rather

the fact that the

by active transport of ions across

concentration gradient

just as the

not changing.

is

name comes from

electrical gradient created

the

The membrane po-

fluid is

The

in

the Body

The voltmeter measures

A is

Water and Solutes

Distribution of

recording electrode placed inside the cell

the difference

in

electrical

charge between the inside of a cell and the surrounding solution. This value

membrane

difference, or

The chart recorder measures changes

is

the

potential

Vm

.

membrane

in

potential over time.

Measuring membrane potential difference In the laboratory, a voltmeter measures the difference in electrical Figure 5-37 charge between the inside of a cell and the surrounding solution.

is

not really neutral because

it

has excess positive charges that ex-

actly balance the excess negative charges inside the cell.

body remains

The

total

ions create the resting

animal

cells?

The

artificial cell

the only force acting on K~ were the concentration gradi-

If

ent,

Which

a negative charge inside the cell as K

diffuses out of the cell.

electrically neutral at all times.

The Resting Membrane Potential Is Due Mostly to Potassium

up

proteins gradually build

+ K would

leak out of the cell until the K* concentration in-

side the cell equaled the K" concentration outside. But the loss of

positive ions

membrane potential difference in shown in Figure 5-36b used an ac-

from the

cell creates

back into the

K

cell.

Thus,

down

cal gradient?

the negative charge inside the

Real cells are not completely

impermeable

to

all

ions.

They

have open channels and protein transporters that allow ions to

move between

the cytoplasm and the extracellular fluid.

use a different

artificial cell to

show how the

resting

We

can

membrane

(Fig.

tem

whose membrane

5-38a#) contains K

teins,

Cl~.

artificial cell

represented by Pr

Both the is

cell

.

+

impermeable

is

cell is

and solution

in electrical equilibrium.

placed in a solution of

are electrically neutral

However,

it is

not in

librium. There are concentration gradients for in the system,

and they would

concentration gradients In Figure 5-38b, a

brane,

making

it

if

K+

all

diffuse

all

leak channel

is

and the

sys-

chemical equi-

four types of ions

down

they could cross the

Na + and

cell

some point

cell,

moving down

some

dig. 5-38