Principles of human physiology 6e global edition stanfield 1

PRINCIPLES OF Human Physiology Sixth Edition Global Edition CINDY L STANFIELD University of South Alabama )BSMPX
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.JMBO Senior Acquisitions Editor: Kelsey Churchman Program Manager: Chriscelle Palaganas Project Manager: Chakira Lane Director of Development: Barbara Yien Editorial Assistant: Ashley Williams Content Producer: Joe Mochnick Text and Photo Permissions Project Manager: Tim Nicholls Program Management Team Lead: Mike Early Project Management Team Lead: Nancy Tabor Assistant Acquisitions Editor, Global Edition: Aditee Agarwal Assistant Project Editor, Global Edition: Shaoni Mukherjee Manager, Media Production, Global Edition: Vikram Kumar Senior Manufacturing Controller, Production, Global Edition: Trudy Kimber Managing Editor: Angel Chavez Design Manager: Marilyn Perry Text Designer: Emily Friel Marketing Manager: Allison Rona Senior Manufacturing Buyer: Stacey Weinberger Cover Photo Credit: Pan Xunbin Credits and acknowledgments for materials borrowed from other sources and reproduced, with permission, in this textbook appear on the appropriate page within the text in the case of art or text material and on p 758 in the case of photos Pearson Education Limited Edinburgh Gate Harlow Essex CM20 2JE England and Associated Companies throughout the world Visit us on the World Wide Web at: www.pearsonglobaleditions.com © Pearson Education Limited 2017 The rights of Cindy L Stanfield to be identified as the author of this work have been asserted by her in accordance with the Copyright, Designs and Patents Act 1988 Authorized adaptation from the United States edition, entitled Principles of Human Physiology, 6th edition, ISBN 978-0-134-16980-4, by Cindy L Stanfield, published by Pearson Education © 2017 All rights reserved No part of this publication may be reproduced, stored in a retrieval system, or transmitted in any form or by any means, electronic, mechanical, photocopying, recording or otherwise, without either the prior written permission of the publisher or a license permitting restricted copying in the United Kingdom issued by the Copyright Licensing Agency Ltd, Saffron House, 6–10 Kirby Street, London EC 1N 8TS All trademarks used herein are the property of their respective owners The use of any trademark in this text does not vest in the author or publisher any trademark ownership rights in such trademarks, nor does the use of such trademarks imply any affiliation with or endorsement of this book by such owners MasteringA&P®, A&PFlixTM, Interactive Physiology®, and PhysioExTM are trademarks, in the U.S and/or other countries, of Pearson Education, Inc or its affiliates ISBN 10: 1-292-15648-1 ISBN 13: 978-1-292-15648-4 British Library Cataloguing-in-Publication Data A catalogue record for this book is available from the British Library 10 Typeset by Integra Software Services, Inc Printed and bound by Vivar in Malaysia SOL VE IT! Solve It Tutorials How Can Membrane Transport Changes Lead to a Heart Attack? 11 Why Does Mio Keep Falling Down? Part 13 Why Does Mio Keep Falling Down? Part 14 Why Does Mio Keep Falling Down? Part 15 Why Is Marcus Forming Blood Clots and What Problems Can They Cause? 19 Why Does Mio Keep Falling Down? Part 19 What Is Causing Episodes of Muscle Weakness in this Patient?* 19 The Car Accident: How Is Breathing Related to Acid-Base Balance?* 21 How Are Insulin Pathways Involved in Diabetes Pathogenesis and Treatment? 22 Does Sex Determination Have Only Two Possible Outcomes: Male or Female?* 24 How Does Diabetes Pathogenesis Progress? *These Solve It tutorials are not printed in the textbook, but are assignable in MasteringA&P This page intentionally left blank www.freebookslides.com Don’t just read this book… Explore physiology with www.freebookslides.com Don’t just ask questions… NEW! SOLVE IT tutorials engage students in a multi-step case study in which they must analyze real data Students begin by reading a clinical scenario and answering a question in the book, with the opportunity to delve deeper in an assignable activity in MasteringA&P SSOOL L VVEE IITT! ! What Happens in Your Cells During a Heart Attack? Thirty-one-year-old Ahmed was dizzy, sweaty, having trouble catching his breath, and had chest pain radiating in his left arm and lower back From his nursing classes, Ahmed thought these were symptoms of a heart attack; but he was so young Since he was taught to educate patients not to ignore these symptoms, he went to the emergency department He was immediately taken back to a room, had blood drawn, and was connected to an electrocardiogram (ECG) When the attending physician came in, Ahmed learned that he had suffered a heart attack and would be admitted to the hospital The next day, a physician came in to talk to Ahmed about his results in the table to the right Based on the test results, Ahmed has            A hypercholesterolemia and hyperglycemia B hypocholesterolemia and hypoglycemia C hypercholesterolemia and hypoglycemia D hypocholesterolemia and hyperglycemia Blood Test Normal Values Ahmed’s Values Total cholesterol (mg/dL) < 200 mg/dL 350 mg/dL Low-density lipoproteins (LDL) < 130 mg/dL 273 mg/dL Glucose (fasting) 70–110 mg/dL 243 mg/dL Hemoglobin A1C 5.6% or less is normal 7.2% 5.7–6.4% indicates prediabetes > 6.4% confirms diabetes Troponin I (TnI) L) If 1/1000 of a mole (that is, millimole) of solute is dissolved in liter of solution, the concentration is 0.001 molar or millimolar (1 mM = * 10 -3 mol>L) For very dilute solutions, concentrations may be expressed in micromoles per liter (mmol>L = * 10 -6 mol>L) or nanomoles per liter (nmol>L = * 10 -6 mol>L) Concentrations of specific substances are often indicated using brackets For example, 3Na+4 represents sodium ion concentration One should not confuse molarity with molality Molality is the number of moles per kilogram solvent, which in the case of water is liter at 25°C Thus, at 25°C, molarity and molality are approximately the same for aqueous solutions Occasionally, concentrations are expressed in terms of the mass of solute contained in a unit volume of solution—in grams per liter (g/L) or micrograms per liter (mg>L = * 10 -6 g>L), for instance Often in physiology, the unit of volume is a deciliter (dL = 0.1 L), which is equivalent to 100 milliliters (100 mL) The concentration of a solution containing gram of solute per deciliter is frequently expressed as percent (1%) because physiological solutions are mostly water, 100 mL of which weighs 100 grams www.freebookslides.com 92 CHAPTER Cell Metabolism FOCUS ON DIABETES The Law of Mass Action The law of mass action is critical in regulating whole-body metabolism because concentrations of reactants and products in cells and body fluids are constantly changing For example, following a meal, blood glucose levels increase as glucose is absorbed from the gastrointestinal tract into the blood In response, the hormone insulin is released into the bloodstream and travels to various cells in the body to increase glucose uptake into these cells During this post-absorptive state, body cells have ample glucose to use it as their primary source of energy In diabetes no net reaction An equilibrium constant greater than indicates an exergonic reaction in which the net reaction proceeds to the right An equilibrium constant less than indicates an endergonic reaction in which the net reaction proceeds to the left Because K is a constant, an increase in the concentration of reactant would drive the reaction to the right—that is, more product would be produced Likewise, an increase in the concentration of product would drive the reaction to the left; therefore, less product would be produced or the reaction could go in reverse This phenomenon is commonly referred to as the law of mass action As it relates to physiology, the law of mass action can be stated more simply as follows: An increase in the concentration of reactants relative to products tends to push a reaction forward, and an increase in the concentration of products relative to reactants tends to push a reaction in reverse Apply Your Knowledge Given a chemical reaction, reactant L product, the equilibrium constant can be calculated as follows: K = 3product4 3reactant4 If the equilibrium constant is 2, then what is the ratio of reactant to product when the reaction is at equilibrium? Is this an exergonic or endergonic reaction? Answer the same questions for equilibrium constants of 10, 0.1, and 0.01 Chemical equilibrium and the law of mass action are illustrated in Figure 3.2 The two graphs show the change in the concentration of reactant and product for a simple reaction (reactant L product) over time The slope of the curve represents the rate of reaction, with a greater slope indicating a faster rate In Figure  3.2a, the reaction is allowed to proceed until equilibrium This reaction is exergonic because more product than reactant is present at equilibrium In Figure 3.2b, the reaction proceeds to equilibrium, but then more reactant is added Addition of more reactant drives the formation of more product until equilibrium is again established mellitus, however, insulin level or activity is low, such that levels of glucose inside cells remain low, even in the post-absorptive state Thus glucose metabolism is slow and the cell must turn to other molecules as sources of energy, such as lipids and proteins Activation Energy When reactant molecules enter into a reaction, their conversion into product molecules does not occur abruptly Instead, the reacting molecules go into a high-energy intermediate form called a transition state, which then breaks down into the products The reverse reaction (the conversion of products to reactants) also must go through this transition state Thus the transformations that occur in a reaction are continuous and gradual, not sudden, as shown in Figure 3.3a The “hump” in the middle of the curve, known as an activation energy barrier, arises because the potential energy of the transition state is greater than that of either the reactants or the products For example, we previously described the burning of paper as an energy-releasing process However, paper does not spontaneously combust Instead, energy, such as a flame or heat provided through a magnifying glass, is required to initiate this process by overcoming the activation energy barrier For reactants to become products, or vice versa, molecules must have sufficient potential energy to surmount the activation energy barrier To so, they must acquire some “extra” energy, called activation energy, which is the difference between the energy of the transition state and the energy of either the reactants or the products The activation energy is indicated in Figure 3.3b as the vertical distance between the initial or final energies and the peak of the curve Note that for the exergonic reaction shown in the figure, the activation energy for the forward reaction is less than the activation energy for the reverse reaction For an endergonic reaction, the reverse would be true If molecules must acquire extra energy to surmount the activation energy barrier and react, where does this “extra” energy come from? Molecules acquire this energy by colliding with one another, which happens all the time because they are in constant thermal motion Consider, for example, the reaction A + B S C + D For molecules of A and B to react, they first must collide When this happens, some of the molecules’ thermal kinetic energy is converted to potential energy If this gain in potential energy is equal to or greater than the activation energy, then the two molecules will enter the transition state and be converted to the products C and D (Figure 3.4a) www.freebookslides.com CHAPTER Cell Metabolism 93 Activation energy barrier Energy Concentration Reactant Reactants Product Products Time (a) Extent of reaction Add reactant (a) Energy Concentration Reactant Reactants Forward activation energy Product Time Reverse activation energy (b) Figure 3.2 Chemical equilibrium and the law of mass action For a simple exergonic reversible reaction with one reactant converted to one product (reactant L product), the concentrations of reactant (green line) and product (red line) are plotted over time (a) The reaction is allowed to proceed to equilibrium (b) After reaching equilibrium, more reactant is added, which, by the law of mass action, causes the production of more product The significance of the activation energy barrier is that it limits how fast a reaction can go, a topic that is explored in detail in the next section Note, however, that not every collision between reactant molecules produces a reaction, because some collisions not generate enough potential energy to surmount the activation energy barrier The more quickly two molecules about to collide are moving, the more potential energy they gain in the collision If the energy gained is less than the activation energy, then the colliding molecules will not enter the transition state and will not react (Figure 3.4b); instead, they will emerge from the collision unaltered Quick Check 3.2 ➊ In an exergonic reaction, which has more energy—the reactants or the products? ➋ Which factor determines the direction of a reaction? Are reactions that go forward spontaneously exergonic or endergonic? ➌ ➍ Give a brief description of the law of mass action What is activation energy? How does it affect a reaction? Products Extent of reaction (b) Figure 3.3 The activation energy barrier The reactions depicted are energy-releasing reactions (a) An energy diagram similar to that in Figure 3.1a, but with the activation energy barrier included (b) An energy diagram in which the forward and reverse activation energies are indicated by the vertical arrows 3.3 Reaction Rates The rate of a chemical reaction is a measure of how fast it consumes reactants and generates products; it is usually expressed as a change in concentration per unit time (moles/liter-second, or some equivalent) For example, as the reaction A + B S C + D proceeds, the concentrations of A and B diminish while the concentrations of C and D increase The rate of this reaction can be expressed as the change in the concentrations of C or D per unit time The rate of a metabolic reaction is of great physiological significance because proper body function demands that reactions proceed at a rate that matches the body’s needs at the moment Rates higher or lower than required ultimately lead to severe impairment of cellular function Perhaps the most vivid demonstration of this danger occurs in hypothermia, when body temperature falls below normal Any decline in body temperature causes metabolic reactions to slow down, and a decline in core temperature of only a few degrees can cause a person to become weak and disoriented, and possibly even to lose consciousness A  further www.freebookslides.com 94 CHAPTER Cell Metabolism A B Factors Affecting the Rates of Chemical Reactions C Transition state D Energy A+B A+B C+D Reactant and Product Concentrations C+D Extent of reaction (a) A A B B Energy A+B A+B A+B We know from experience that certain chemical reactions progress more quickly than others For example, one oxidation reaction—the combustion of gasoline—can occur with explosive speed, whereas the rusting of iron (another oxidation reaction) occurs so slowly that it may take weeks to see the effects The rate of a reaction is determined by a variety of factors, including (1) reactant and product concentrations, (2) temperature, and (3) the height of the reaction’s activation energy barrier C+D When we speak of the rate of a reaction, we are usually referring to its net rate: the difference between the rate of the forward reaction (reactants S products) and the rate of the reverse reaction (products S reactants) According to the law of mass action, any increase in the concentration of reactants will bring about an increase in the forward rate without affecting the reverse rate Likewise, any increase in the concentration of products will cause the reverse rate to increase without affecting the forward rate Therefore, an increase in the concentration of reactants relative to products will increase the net rate in the forward direction Conversely, an increase in the concentration of products relative to reactants will decrease the net forward rate and, if the change in concentration is large enough, can even make the reaction go in reverse The effect of reactant and product concentrations on reaction rates reflects the fact that concentrations affect the frequency of collisions between molecules: As the concentration of molecules increases, the number of collisions occurring in a given time period also increases Temperature Extent of reaction (b) Figure 3.4 Effect of the activation energy barrier (a) Collision of two reactant molecules, A and B, with enough energy to enter the transition state The energy of the collision surmounts the activation energy barrier, resulting in the formation of products C and D (b) Collision of A and B with insufficient energy to enter the transition state The activation energy barrier is not surmounted, so no reaction occurs In general, the rate of a reaction increases with increasing temperature and decreases as the temperature falls We refrigerate food, for example, because cooling slows down the rate of decomposition reactions, which helps the food “keep” longer Temperature influences reaction rates because it affects the frequency and energy of molecular collisions As temperature increases, the average kinetic energy of molecules increases, which increases the energy of collisions The result is an increase in the proportion of collisions having enough energy to surmount the activation energy barrier, which in turn increases the rate of a reaction Q As the activation energy barrier is lowered, does the energy change in the reaction increase, decrease, or stay the same? drop in temperature can precipitate cardiac arrest (stoppage of the heartbeat) and death Later in this section, we will see that metabolic reactions are accelerated or catalyzed by special molecules called enzymes, and that the rates of metabolic reactions are normally regulated through changes in enzyme activity First, however, we begin our exploration of reaction rates by examining the factors that affect the rates of chemical reactions in general The Height of the Activation Energy Barrier The height of the activation energy barrier differs among reactions All else being equal, the rate of a reaction increases as the height of the barrier decreases The reason for this is that at any given temperature, only a fraction of the collisions between molecules have sufficient energy to surmount the barrier and produce a reaction (Figure 3.5) As the height of the barrier decreases, the proportion of collisions having the requisite energy increases—not because the collisions themselves are any more energetic, but because the minimum energy requirement for a “successful” collision has been www.freebookslides.com CHAPTER High activation energy barrier Number of reactants Low activation energy barrier reduced (This situation is analogous to a high-jump competition: If the bar is lowered, the number of contestants making a successful jump will increase.) Note that as the height of the activation energy barrier decreases, rates of both the reverse reaction and the forward reaction increase because the activation energy of both reactions becomes lower The net rate of the reaction still increases, despite the increase in the rate of the reverse reaction; this trend occurs for reasons beyond the scope of this book Enzyme Reaction Catalyzed RNA polymerase DNA uncoiling and synthesis of RNA DNA polymerase DNA uncoiling and synthesis of DNA Protein kinase Phosphorylation of a protein Phosphoprotein phosphatase Dephosphorylation of a protein Catalase Breakdown of hydrogen peroxide to water and oxygen Hexokinase Phosphorylation of glucose ATP synthase Synthesis of ATP through oxidative phosphorylation Lactate dehydrogenase Conversion of lactic acid to pyruvic acid Glucose-6-phosphatase Removal of phosphate from glucose-6-phosphate Carbonic anhydrase Conversion of carbonic acid to water and carbon dioxide Amylase Breakdown of complex carbohydrates Lipase Breakdown of triglycerides to monoglycerides and fatty acids Sucrase Breakdown of sucrose to glucose and fructose the substrate to generate a product molecule, which is subsequently released Thus the action of the enzyme can be written as a two-step reaction: E The Role of Enzymes in Chemical Reactions If you were to set up a typical metabolic reaction by mixing reactants together in a beaker, it would proceed very slowly In fact, most metabolic reactions would proceed too slowly to be compatible with life These reactions are able to proceed at considerably faster rates in cells because of the presence of enzymes, biomolecules (almost always proteins) specialized to act as catalysts, a general term for substances that increase the rates of chemical reactions In this section, we examine how enzymes accomplish this task and how the regulation of enzyme activity controls reaction rates according to the body’s needs Mechanisms of Enzyme Action Cells contain a wide variety of enzymes, each specialized to catalyze a particular reaction or group of related reactions (Table 3.1 lists some of the key enzymes found in the human body, along with their functions.) To catalyze a reaction, an enzyme molecule must first bind to a reactant molecule, which in the context of enzymecatalyzed reactions is called a substrate The enzyme then acts on 95 TABLE 3.1 Sample of Enzymes Energy of reactants Figure 3.5 Energy of reactant molecules The energy of individual reactant molecules varies, but roughly follows a bell-shaped population curve For reactants to be converted to products, their energy must be greater than the activation energy barrier If the activation energy barrier is relatively low, a higher proportion of reactants will have enough energy to be converted to product (all reactants to the right of the low activation energy barrier line on the graph) In contrast, when the activation energy barrier is relatively high, few reactants will have enough energy to be converted to product (only those reactants with energy above the high activation energy barrier line on the graph) Cell Metabolism enzyme + S substrate L E#S enzymesubstrate complex L P product + E enzyme The double arrow in the first step (the binding step) signifies that it is possible for the substrate to bind to the enzyme and then be released before the enzyme has a chance to act on it (see Figure 3.6a) Such binding is said to be reversible because the substrate interacts with the protein through weak interactions and can readily dissociate from the enzyme after binding to it (Toolbox: Ligand-Protein Interactions, p 97) If the substrate molecule stays bound to the enzyme long enough, it will eventually be converted to product in the second step (the catalytic step) After the catalytic step, the enzyme molecule emerges from the reaction in the same form as it entered, indicating that it is neither consumed nor otherwise altered in the reaction The enzyme is then free to act on a new substrate molecule and generate another product In fact, a single enzyme molecule is capable of catalyzing a reaction repeatedly and theoretically could generate an unlimited quantity of product As indicated by the double arrow, the enzyme can also catalyze the reaction in reverse, such that the product is converted back to substrate www.freebookslides.com 96 CHAPTER Cell Metabolism Enzyme free to bind with substrate molecule In reality, most enzymes act on two or more different substrates and generate more than one product Enzyme E Active site Substrate Specificity S Substrate S Substrate binds to enzyme molecule Substrate may leave active site unchanged P E S Product leaves enzyme Enzyme-substrate complex E P (a) Substrate may be converted to product by enzyme Product Enzyme E Active site SA SD Substrate A Substrate D SB SC Substrate B Substrate C (b) Figure 3.6 The role of substrate specificity in the mechanism of enzyme action (a) The mechanism of enzyme action The closeness of fit between substrate molecule S and the enzyme’s active site enables binding and the formation of an enzyme-substrate complex After binding, the substrate may leave the active site unchanged, or it may be converted to product P by the enzyme The product then exits the active site, leaving the enzyme free to bind another substrate molecule and catalyze the reaction again (b) Substrate specificity Because only the shape of candidate substrate SC is complementary to the enzyme’s active site, only it can bind with the enzyme Although the preceding reaction illustrates the essentials of enzyme action, it pertains to only the simplest type of enzymatic reaction, in which an enzyme acts on just one substrate molecule at a time to generate a single product, as expressed in the following shorthand notation: E S ¡ P Enzymes are generally able to catalyze one particular reaction because they have the ability to “recognize” and bind to only one particular type of substrate, a phenomenon referred to as substrate specificity This specificity is not necessarily absolute, however: Some enzymes are able to act on a wide variety of substrate molecules as long as they have certain characteristics One example is pepsin, an enzyme that is secreted by cells in the stomach lining and breaks proteins in food into smaller polypeptide fragments Pepsin can act on almost any protein, so long as the protein contains certain amino acids, but it cannot act on other constituents of food, such as fats or carbohydrates The basis of substrate specificity relates to the complementary shapes of the enzyme and substrate molecules: Only if a substrate molecule closely fits and binds to a particular site on the enzyme molecule, called the active site, can the enzyme act on the substrate and catalyze the reaction As illustrated in Figure 3.6b, uncomplementary “candidate” substrate molecules cannot fit into the active site very well and, therefore, are not acted upon by the enzyme Two models currently describe the mechanism of enzyme binding: the lock-and-key model (Figure 3.6) and the inducedfit model (Figure 3.7) In the lock-and-key model, the substrate matches the active site just as a key matches a lock, with this relationship explaining substrate specificity The downside of this model is that it does not explain the reversibility of most enzymecatalyzed reactions—if the enzyme fits the substrate, then it cannot also fit the product for the reverse reaction The newer inducedfit model is more amenable to explaining reversible reactions In this model, the substrate fits the active site more like a foot fits a sock than like a lock fits a key; the shapes are similar but not precisely complementary When the substrate binds to the enzyme, it induces a conformational change in the enzyme to produce a better fit, much like a foot inside a sock makes the sock take on the shape of the foot Cofactors and Coenzymes Although enzymes are proteins, many possess additional nonprotein components called cofactors, which are necessary for the enzymes to function properly Many enzymes contain metal ions such as iron, copper, and zinc, which function as cofactors by Product Substrate S Substrate S E P E E Enzyme P Product Enzyme E Enzyme Figure 3.7 Induced-fit model of enzyme activity In this model, both the substrate and the product can bind to the active site, allowing the reaction to proceed in reverse Enzyme www.freebookslides.com CHAPTER Cell Metabolism TOOLBOX Ligand-Protein Interactions When a substrate binds to an enzyme, it does so through weak interactions (hydrogen bonds, ionic bonds, and van der Waals forces, but not covalent bonds) Molecules that interact with proteins in this manner are called ligands Thus we can generalize the interaction between proteins and ligands as a reversible reaction: The strength of the interaction between a protein and a ligand, called affinity, depends on the degree of complementary shape and the number and strength of the chemical interactions In the following example, ligand A forms more ionic bonds with the protein than ligand B Therefore, the protein has a greater affinity for ligand A protein + ligand L protein ¬ ligand Ligands can bind to proteins because they have a shape complementary to a portion of the protein, called the binding site, much like a key has a complementary shape to a lock Ligands are also chemically attracted to protein binding sites The binding between a ligand and a protein is specific because only certain ligands fit the binding site + – – – Binding site Protein The interaction between proteins and ligands follows the law of mass action—that is, an increase in the amount of either protein or ligand increases the number of proteins with bound ligand This is illustrated in the following graph, which shows the relationship between the number of proteins with bound ligand and the concentration of ligand Two curves are shown, one for a low concentration of protein and one for a higher concentration + – + + + + Protein Ligand B A higher affinity increases the likelihood that a given protein will have a ligand bound to it In terms of a population of proteins, a higher affinity means more proteins will have ligand bound to them This situation is shown in the following graph for the binding of ligand A or B to the protein, assuming only one ligand is present at a time High [protein] Number of bound ligand Ligand A Number of bound ligand Ligand + – + + – – Low [protein] Ligand A Ligand B Ligand concentration Several types of protein-ligand interactions occur in the body, as shown in the following table and discussed throughout the text Ligand concentration Protein Ligand Function Enzyme Substrate Catalyze chemical reactions in the body Enzyme Modulator Allosteric regulation of enzyme activity Receptor Chemical messenger (e.g., neurotransmitters, hormones) Communicate messages between cells Carrier Solute Transport solutes across plasma membranes Carrier Solute Transport solutes in blood 97 www.freebookslides.com 98 CHAPTER Cell Metabolism binding tightly to the side chains of certain amino acids, thereby holding the enzyme in its normal conformation Without these ions, the enzymes’ shapes would be altered, causing them to lose their activity Other enzymes contain vitamins (various organic molecules of which only trace amounts are required for proper functioning of the body, but which must be obtained through the diet) or vitamin derivatives as cofactors Apply Your Knowledge Alcohol dehydrogenase, an enzyme found in the stomach and liver, removes ethanol from the body by oxidizing it to acetaldehyde Zinc is a cofactor for alcohol dehydrogenase If a person’s intake of zinc were deficient, how would this deficiency affect the activity of alcohol dehydrogenase and the person’s ability to tolerate alcohol? Some vitamin-derived cofactors function as coenzymes, molecules that not themselves have catalytic activity but nonetheless participate directly in the reactions catalyzed by their enzyme partners A given coenzyme may be used by more than one type of enzyme; often a coenzyme can dissociate from one enzyme and bind to another, enabling it to participate in more than one reaction In a few cases, coenzymes are permanently bound to their partner enzymes Usually a coenzyme carries particular chemical groups from one reaction to another Like enzymes, coenzymes are not permanently altered by the reactions in which they participate and, therefore, can be used over and over again Three coenzymes are particularly important in energy metabolism: flavin adenine dinucleotide (FAD), a derivative of vitamin B2 (riboflavin); nicotinamide adenine dinucleotide (NAD), a derivative of vitamin B3 (niacin); and coenzyme A (CoA), a derivative of vitamin B5 (pantothenic acid) FAD and NAD participate as hydrogen (electron) carriers in certain oxidation-reduction reactions, shuttling electrons from one place to another inside cells FAD acquires electrons by picking up pairs of hydrogen atoms and in the process becomes reduced to FADH2: another pair of electrons We will see several examples of NAD + and FAD at work later in the chapter CoA picks up chemical groups called acetyl groups (¬ CH2COOH) in certain metabolic reactions and carries them to other reactions In the process, each CoA becomes covalently bound to an acetyl group, forming a compound called acetylcoenzyme A (acetyl CoA) The role of CoA in glucose oxidation is described later in this chapter Factors Affecting the Rates of Enzyme-Catalyzed Reactions Enzymes accelerate metabolic reactions by reducing the height of the activation energy barrier This relationship can be seen in Figure 3.5, by considering the high activation energy level in the absence of enzyme and the low activation energy level in the presence of enzyme Clearly, more molecules have sufficient energy to overcome the activation energy barrier in the presence of enzyme Note that the height of the activation energy barrier does not affect the overall energy change of a reaction (∆E ), which depends only on the difference in energy between reactants and products Therefore, enzymes cannot affect either the direction of a reaction or the amount of energy it releases or requires; instead, they can affect only the rate at which a reaction occurs The rate at which an enzyme can catalyze a reaction is, in turn, affected by several factors, including (1) the enzyme’s catalytic rate, (2) the substrate concentration, (3) the enzyme concentration, and (4) the affinity of the enzyme for the substrate Catalytic Rate The catalytic rate of an enzyme is a measure of how many product molecules it can generate per unit time, assuming that the active site is always occupied by a substrate molecule As such, the catalytic rate reflects how fast an enzyme can carry out the catalytic step of the two-step sequence previously described Some enzymes are inherently faster than others in catalyzing reactions and can convert thousands of substrate molecules into products each second; other enzymes might take more than a minute to act on a single substrate molecule Other things being equal, the rate of an enzymatic reaction increases as the enzyme’s catalytic rate increases FAD + H S FADH2 Subsequently, FADH2 releases these electrons to other electron acceptors In so doing, it reverts to its oxidized form, FAD, which is then free to pick up another pair of electrons NAD + also carries pairs of electrons, but in a different manner: It picks up one electron in a hydrogen atom and the other as a free electron, which it takes from a hydrogen atom, leaving a hydrogen ion (H+) in solution Thus the reduction of NAD + occurs as follows: NAD + + H S NADH + H+ In this process, NAD +, which carries a single positive charge, is reduced to NADH, which carries no charge (The positive charge is canceled by the negative charge of the acquired electron.) Subsequently, NADH releases its pair of electrons to other electron acceptors through the reverse of the previous reaction and is transformed into the oxidized form NAD +, which is free to pick up Substrate Concentration The rate of an enzyme-catalyzed reaction increases as the substrate concentration increases based on the law of mass action An increase in the number of substrate molecules increases the likelihood that a substrate will be bound to an enzyme—and an enzyme can catalyze a reaction only when substrate is bound to it In addition, an enzyme can be used over again Once one substrate has been converted to product and the product released, the enzyme can bind to another substrate and convert it to product Thus, when the substrate concentration is low, more time will pass before the next substrate molecule binds to the enzyme, and as a result its active site will remain unoccupied for a greater percentage of the time Under these conditions, the reaction rate will be low because for much of the time the enzyme is idle By comparison, at higher substrate concentrations, less time will pass before the next substrate molecule comes along This means that the enzyme’s active site will be occupied more of the time, which gives the www.freebookslides.com CHAPTER High [E] Maximum rates Reaction rate Low [E] Cell Metabolism 99 Figure 3.8 shows two curves, one for a low concentration of enzyme and the other for a higher concentration Note that for any given concentration of substrate, the reaction rate is faster for the higher concentration of enzyme Also note that even though a maximum reaction rate occurs under both concentrations of enzyme, the maximum reaction rate is faster when the concentration of enzyme is greater Affinity The affinity of an enzyme is a measure of how tightly sub- Figure 3.8 Influence of substrate concentration on the rate of an enzyme-catalyzed reaction Binding of substrate to the enzyme increases with increasing [S] until high substrate concentrations are reached, in which case all enzyme molecules are bound (100% saturation) At a higher concentration of enzyme, more substrate can bind enzyme and a faster reaction rate will be achieved Q As the reaction rate is increasing, is the concentration of free (unbound) enzyme molecules increasing or decreasing? enzyme more opportunity to catalyze the reaction Consequently, the reaction rate will be higher Figure 3.8 shows how the rate of an enzyme-catalyzed reaction varies with the substrate concentration, [S], and enzyme concentration At lower and moderate concentrations, the rate of the reaction increases as [S] increases, as we would expect At higher concentrations, however, the curve levels off, indicating that further increases in [S] fail to raise the rate appreciably Given a fixed enzyme concentration, when [S] is very high, the active site of every enzyme molecule is occupied by substrate virtually 100% of the time, and the enzyme is said to be 100% saturated (The percent saturation of an enzyme indicates the proportion of time that the active site is occupied; thus, at 25% saturation, the active site is occupied 25% of the time.) Raising [S] beyond this point does not cause any further increase in the rate because all of the enzyme molecules are already bound to substrates and are already catalyzing the formation of products Under these conditions, the rate of the reaction is limited only by the enzyme’s catalytic rate and its concentration When the concentration of enzyme increases, the reaction can occur at a faster rate for any given concentration of substrate, as described next Enzyme Concentration The catalytic rate of an enzyme influences the rate of an enzymatic reaction by determining how fast individual enzyme molecules can convert substrates to products In addition, the rate of an enzymatic reaction increases in direct proportion to the enzyme concentration based on the law of mass action As described earlier for substrate concentration, an increase in the number of enzyme molecules increases the likelihood that a substrate will be bound to an enzyme and, therefore, converted to product Because enzymes are proteins, enzyme concentration may be varied by regulating the rate of protein synthesis and degradation, as described in Chapter Enzyme with high affinity for substrate Enzyme with low affinity for substrate Difference in reaction rate at low [S] Reaction rate Substrate concentration [S] strate molecules bind to its active site (Affinity is a general term referring to the attraction between two objects.) Generally speaking, higher affinities translate into higher rates for enzyme-catalyzed reactions This makes intuitive sense when you consider that an enzyme’s active site must be occupied by a substrate molecule before the enzyme can catalyze any reaction When substrate molecules are present at a given concentration, an enzyme’s active site will be occupied a greater percentage of the time if the enzyme has a high affinity for the substrate If the affinity is lower, the active site will be occupied for less of the time, all else being equal Therefore, a high-affinity enzyme is able to generate more product molecules in a given length of time A high affinity implies a close fit between an enzyme’s active site and a substrate molecule Such a fit maximizes the area of contact between substrate and enzyme, thereby maximizing any attractive forces that might exist between the two Affinity is also influenced by other factors that increase this force of attraction, such as the presence of opposite electrical charges on the enzyme and the substrate Figure 3.9 shows how the degree of saturation of an enzyme and, hence, the rate at which it can catalyze a reaction are affected not only by the substrate concentration but also by the affinity of the enzyme for the substrate At a given substrate concentration, an enzyme with higher affinity will exhibit a higher degree of saturation than will an enzyme with lower affinity, so it reaches its maximum rate at lower substrate concentrations The maximum rate for a given concentration of enzyme will not be altered, however Low [S] Substrate concentration [S] Figure 3.9 Influence of enzyme-substrate affinity on the rate of an enzyme-catalyzed reaction Plots of reaction rate versus substrate concentration are shown for two enzymes having different affinities for the substrate For purposes of comparison, it is assumed that the two enzymes have the same catalytic rate and are present at the same concentration Note that at lower substrate concentrations, the enzyme with higher affinity is able to catalyze the reaction at a faster rate .. .PRINCIPLES OF Human Physiology Sixth Edition Global Edition CINDY L STANFIELD University of South Alabama )BSMPX
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