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141
An Introduction to Metabolism
The Energy of Life
T
he living cell is a chemical factory in miniature, where thousands of reactions occur within a microscopic space. Sugars can be converted to amino acids that are linked together into proteins when needed. Conversely, when food is di- gested, proteins are dismantled into amino acids that can be converted to sugars. In multicellular organisms, many cells export chemical products that are used in other parts of the organism. The process called cellular respiration drives this cellular economy by extracting the energy stored in sugars and other fuels. Cells apply this energy to perform various types of work, such as the transport of sol- utes across the plasma membrane, which we discussed in Chapter 7. In a more exotic example, the ocean waves shown in Figure 8.1 are brightly illuminated from within by free-floating, single-celled marine organisms called dinoflagellates. These dinoflagellates convert the energy stored in certain organic molecules to light, a process called bioluminescence. Most bioluminescent organ- isms are found in the oceans, but some exist on land, such as the bioluminescent fungus seen at the lower left. Bioluminescence and other metabolic activities car- ried out by a cell are precisely coordinated and controlled. In its complexity, its ef- ficiency, and its responsiveness to subtle changes, the cell is peerless as a chemical factory. The concepts of metabolism that you learn in this chapter will help you understand how matter and energy flow during life’s processes and how that flow is regulated.
▲ Figure 8.1 What causes these breaking waves to glow?
141
K e y C o n C e p t s
8.1 An organism’s metabolism
transforms matter and energy, subject to the laws of thermodynamics
8.2 The free-energy change of
a reaction tells us whether or not the reaction occurs spontaneously
8.3 ATP powers cellular work by
coupling exergonic reactions to endergonic reactions
8.4 Enzymes speed up metabolic
reactions by lowering energy barriers
8.5 Regulation of enzyme activity
helps control metabolism
142 U n i t t w o The Cell
metabolic processes, a basic knowledge of energy is necessary to understand how the living cell works. Although we will use some nonliving examples to study energy, the concepts demonstrated by these examples also apply to bioenergetics , the study of how energy flows through living organisms.
Forms of Energy Energy is the capacity to cause change. In everyday life, en- ergy is important because some forms of energy can be used to do work—that is, to move matter against opposing forces, such as gravity and friction. Put another way, energy is the ability to rearrange a collection of matter. For example, you expend energy to turn the pages of this book, and your cells expend energy in transporting certain substances across membranes. Energy exists in various forms, and the work of life depends on the ability of cells to transform energy from one form to another. Energy can be associated with the relative motion of ob- jects; this energy is called kinetic energy. Moving objects can perform work by imparting motion to other matter: A pool player uses the motion of the cue stick to push the cue ball, which in turn moves the other balls; water gushing through a dam turns turbines; and the contraction of leg muscles pushes bicycle pedals. Thermal energy is kinetic energy associated with the random movement of atoms or molecules; thermal energy in transfer from one object to another is called heat. Light is also a type of energy that can be harnessed to perform work, such as powering photosyn- thesis in green plants. An object not presently moving may still possess energy. Energy that is not kinetic is called potential energy ; it is energy that matter possesses because of its location or struc- ture. Water behind a dam, for instance, possesses energy because of its altitude above sea level. Molecules possess energy because of the arrangement of electrons in the bonds between their atoms. Chemical energy is a term used by biologists to refer to the potential energy available for re- lease in a chemical reaction. Recall that catabolic pathways release energy by breaking down complex molecules. Biolo- gists say that these complex molecules, such as glucose, are high in chemical energy. During a catabolic reaction, some bonds are broken and others formed, releasing energy and resulting in lower-energy breakdown products. This trans- formation also occurs in the engine of a car when the hydro- carbons of gasoline react explosively with oxygen, releasing the energy that pushes the pistons and producing exhaust. Although less explosive, a similar reaction of food molecules with oxygen provides chemical energy in biological systems, producing carbon dioxide and water as waste products. Biochemical pathways, carried out in the context of cellular structures, enable cells to release chemical energy from food molecules and use the energy to power life processes.
C O N C E P T 8.
An organism’s metabolism transforms
matter and energy, subject to the laws
of thermodynamics
The totality of an organism’s chemical reactions is called metabolism (from the Greek metabole, change). Metabo- lism is an emergent property of life that arises from orderly interactions between molecules.
Organization of the Chemistry of Life into
Metabolic Pathways
We can picture a cell’s metabolism as an elaborate road map of the thousands of chemical reactions that occur in a cell, arranged as intersecting metabolic pathways. A metabolic pathway begins with a specific molecule, which is then altered in a series of defined steps, resulting in a certain product. Each step of the pathway is catalyzed by a specific enzyme:
A B C D
Enzyme 1 Enzyme 2 Enzyme 3
Starting molecule
Reaction 1 Reaction 2 Reaction 3 Product
Analogous to the red, yellow, and green stoplights that con- trol the flow of automobile traffic, mechanisms that regulate enzymes balance metabolic supply and demand. Metabolism as a whole manages the material and energy resources of the cell. Some metabolic pathways release en- ergy by breaking down complex molecules to simpler com- pounds. These degradative processes are called catabolic pathways , or breakdown pathways. A major pathway of catabolism is cellular respiration, in which the sugar glucose and other organic fuels are broken down in the presence of oxygen to carbon dioxide and water. (Pathways can have more than one starting molecule and/or product.) Energy that was stored in the organic molecules becomes available to do the work of the cell, such as ciliary beating or mem- brane transport. Anabolic pathways , in contrast, consume energy to build complicated molecules from simpler ones; they are sometimes called biosynthetic pathways. Examples of anabolism are the synthesis of an amino acid from sim- pler molecules and the synthesis of a protein from amino acids. Catabolic and anabolic pathways are the “downhill” and “uphill” avenues of the metabolic landscape. Energy released from the downhill reactions of catabolic pathways can be stored and then used to drive the uphill reactions of anabolic pathways. In this chapter, we will focus on mechanisms common to metabolic pathways. Because energy is fundamental to all
144 U n i t t w o The Cell
spontaneous does not imply that the process would occur quickly; rather, the word signifies that it is energetically favorable. (In fact, it may be helpful for you to think of the phrase “energetically favorable” when you read the formal term “spontaneous.”) Some spontaneous processes, such as an explosion, may be virtually instantaneous, while others, such as the rusting of an old car over time, are much slower. A process that, considered on its own, leads to a decrease in entropy is said to be nonspontaneous: It will happen only if energy is supplied. We know from experience that certain events occur spontaneously and others do not. For instance, we know that water flows downhill spontaneously but moves uphill only with an input of energy, such as when a machine pumps the water against gravity. Some energy is inevitably lost as heat, increasing entropy in the surroundings, so usage of energy ensures that a nonspontaneous process also leads to an increase in the entropy of the universe as a whole.
Biological Order and Disorder
Living systems increase the entropy of their surroundings, as predicted by thermodynamic law. It is true that cells create ordered structures from less organized starting materials. For example, simpler molecules are ordered into the more complex structure of an amino acid, and amino acids are ordered into polypeptide chains. At the organismal level as well, complex and beautifully ordered structures result from biological processes that use simpler starting materials (Figure 8.4). However, an organism also takes in organized forms of matter and energy from the surroundings and re- places them with less ordered forms. For example, an animal obtains starch, proteins, and other complex molecules from the food it eats. As catabolic pathways break these molecules down, the animal releases carbon
▲ Figure 8.4 Order as a characteristic of life. Order is evident in the detailed structures of the sea urchin skeleton and the succulent plant shown here. As open systems, organisms can increase their order as long as the order of their surroundings decreases.
What happens to this energy after it has performed work? The second law of thermodynamics helps to answer this question.
The Second Law of Thermodynamics
If energy cannot be destroyed, why can’t organisms simply recycle their energy over and over again? It turns out that during every energy transfer or transformation, some energy becomes unavailable to do work. In most energy transfor- mations, more usable forms of energy are at least partly con- verted to thermal energy and released as heat. Only a small fraction of the chemical energy from the food in Figure 8.3a is transformed into the motion of the brown bear shown in Figure 8.3b; most is lost as heat, which dissipates rapidly through the surroundings. In the process of carrying out chemical reactions that perform various kinds of work, living cells unavoidably con- vert other forms of energy to heat. A system can put this energy to work only when there is a temperature difference that results in thermal energy flowing as heat from a warmer location to a cooler one. If temperature is uniform, as it is in a living cell, then the heat generated during a chemi- cal reaction will simply warm a body of matter, such as the organism. (This can make a room crowded with people uncomfortably warm, as each person is carrying out a multi- tude of chemical reactions!) A logical consequence of the loss of usable energy as heat to the surroundings is that each energy transfer or transfor- mation makes the universe more disordered. Scientists use a quantity called entropy as a measure of disorder, or ran- domness. The more randomly arranged a collection of mat- ter is, the greater its entropy. We can now state the second law of thermodynamics : Every energy transfer or transfor- mation increases the entropy of the universe. Although order can increase locally, there is an unstoppable trend toward randomization of the universe as a whole. In many cases, increased entropy is evident in the physi- cal disintegration of a system’s organized structure. For example, you can observe increasing entropy in the gradual decay of an unmaintained building. Much of the increasing entropy of the universe is less obvious, however, because it takes the form of increasing amounts of heat and less or- dered forms of matter. As the bear in Figure 8.3b converts chemical energy to kinetic energy, it is also increasing the disorder of its surroundings by producing heat and small molecules, such as the CO (^2) it exhales, that are the break- down products of food. The concept of entropy helps us understand why certain processes are energetically favorable and occur on their own. It turns out that if a given process, by itself, leads to an increase in entropy, that process can proceed without re- quiring an input of energy. Such a process is called a spon- taneous process. Note that as we’re using it here, the word
C h a p t e r 8 An Introduction to Metabolism 145
dioxide and water—small molecules that possess less chemical energy than the food did (see Figure 8.3b). The depletion of chemical energy is accounted for by heat gen- erated during metabolism. On a larger scale, energy flows into most ecosystems in the form of light and exits in the form of heat (see Figure 1.10). During the early history of life, complex organisms evolved from simpler ancestors. For instance, we can trace the ancestry of the plant kingdom from much simpler organisms called green algae to more complex flowering plants. However, this increase in organization over time in no way violates the second law. The entropy of a particular system, such as an organism, may actually decrease as long as the total entropy of the universe—the system plus its surroundings—increases. Thus, organisms are islands of low entropy in an increasingly random universe. The evolution of biological order is perfectly consistent with the laws of thermodynamics.
C o n C e p t C h e C K 8. 1
- m a k e c o n n e c t i o n s how does the second law of thermodynamics help explain the diffusion of a sub- stance across a membrane? (see Figure 7.10.)
- Describe the forms of energy found in an apple as it grows on a tree, then falls, then is digested by someone who eats it.
- w h a t i F? if you place a teaspoon of sugar in the bot- tom of a glass of water, it will dissolve completely over time. Left longer, eventually the water will disappear and the sugar crystals will reappear. explain these observa- tions in terms of entropy. For suggested answers, see appendix a.
C O N C E P T 8.
The free-energy change of a reaction
tells us whether or not the reaction
occurs spontaneously
The laws of thermodynamics that we’ve just discussed apply to the universe as a whole. As biologists, we want to under- stand the chemical reactions of life—for example, which reactions occur spontaneously and which ones require some input of energy from outside. But how can we know this without assessing the energy and entropy changes in the en- tire universe for each separate reaction?
Free-Energy Change, ΔG
Recall that the universe is really equivalent to “the system” plus “the surroundings.” In 1878, J. Willard Gibbs, a profes- sor at Yale, defined a very useful function called the Gibbs
free energy of a system (without considering its surround- ings), symbolized by the letter G. We’ll refer to the Gibbs free energy simply as free energy. Free energy is the portion of a system’s energy that can perform work when tempera- ture and pressure are uniform throughout the system, as in a living cell. Let’s consider how we determine the free-energy change that occurs when a system changes—for example, during a chemical reaction. The change in free energy, ΔG, can be calculated for a chemical reaction by applying the following equation: ΔG = ΔH - TΔS
This equation uses only properties of the system (the re- action) itself: ΔH symbolizes the change in the system’s enthalpy (in biological systems, equivalent to total energy); ΔS is the change in the system’s entropy; and T is the abso- lute temperature in Kelvin (K) units (K = °C + 273; see Appendix C). Once we know the value of ΔG for a process, we can use it to predict whether the process will be spontaneous (that is, whether it is energetically favorable and will occur without an input of energy). More than a century of experi- ments has shown that only processes with a negative ΔG are spontaneous. For ΔG to be negative, ΔH must be negative (the system gives up enthalpy and H decreases) or TΔS must be positive (the system gives up order and S increases), or both: When ΔH and TΔS are tallied, ΔG has a negative value (ΔG 6 0) for all spontaneous processes. In other words, every spontaneous process decreases the system’s free en- ergy, and processes that have a positive or zero ΔG are never spontaneous. This information is immensely interesting to biologists, for it gives us the power to predict which kinds of change can happen without an input of energy. Such spontaneous changes can be harnessed to perform work. This principle is very important in the study of metabolism, where a major goal is to determine which reactions can supply energy for cellular work.
Free Energy, Stability, and Equilibrium As we saw in the previous section, when a process occurs spontaneously in a system, we can be sure that ΔG is nega- tive. Another way to think of ΔG is to realize that it repre- sents the difference between the free energy of the final state and the free energy of the initial state: ΔG = Gfinal state - Ginitial state
Thus, ΔG can be negative only when the process involves a loss of free energy during the change from initial state to final state. Because it has less free energy, the system in its final state is less likely to change and is therefore more stable than it was previously.
C h a p t e r 8 An Introduction to Metabolism 147
reactant and product, 25°C, pH 7), 686 kcal (2,870 kJ) of energy are made available for work. Because energy must be conserved, the chemical products of respiration store 686 kcal less free energy per mole than the reactants. The products are, in a sense, the spent exhaust of a process that tapped the free energy stored in the bonds of the sugar molecules. It is important to realize that the breaking of bonds does not release energy; on the contrary, as you will soon see, it requires energy. The phrase “energy stored in bonds” is shorthand for the potential energy that can be released when new bonds are formed after the original bonds break, as long as the products are of lower free energy than the reactants. An endergonic reaction is one that absorbs free energy from its surroundings (^) (Figure 8.6b). Because this kind of reaction essentially stores free energy in molecules (G in- creases), ΔG is positive. Such reactions are nonspontaneous, and the magnitude of ΔG is the quantity of energy required to drive the reaction. If a chemical process is exergonic (downhill), releasing energy in one direction, then the re- verse process must be endergonic (uphill), using energy. A reversible process cannot be downhill in both directions. If ΔG = - 686 kcal/mol for respiration, which converts glucose and oxygen to carbon dioxide and water, then the reverse process—the conversion of carbon dioxide and water to glu- cose and oxygen—must be strongly endergonic, with ΔG = +686 kcal/mol. Such a reaction would never happen by itself. How, then, do plants make the sugar that organisms use for energy? Plants get the required energy—686 kcal to make a mole of glucose—from the environment by captur- ing light and converting its energy to chemical energy. Next, in a long series of exergonic steps, they gradually spend that chemical energy to assemble glucose molecules.
Equilibrium and Metabolism
Reactions in an isolated system eventually reach equilibrium and can then do no work, as illustrated by the isolated hydro electric system in Figure 8.7. The chemical reactions of metabolism are reversible, and they, too, would reach
with a net release of free energy (Figure 8.6a). Because the chemical mixture loses free energy (G decreases), ΔG is neg- ative for an exergonic reaction. Using ΔG as a standard for spontaneity, exergonic reactions are those that occur spon- taneously. (Remember, the word spontaneous implies that it is energetically favorable, not that it will occur rapidly.) The magnitude of ΔG for an exergonic reaction represents the maximum amount of work the reaction can perform.* The greater the decrease in free energy, the greater the amount of work that can be done. We can use the overall reaction for cellular respiration as an example:
C 6 H12O 6 + 6 O 2 S 6 CO 2 + 6 H 2 O ΔG = - 686 kcal/mol (-2,870 kJ/mol)
For each mole (180 g) of glucose broken down by respiration under what are called “standard conditions” (1 M of each
Progress of the reaction
Progress of the reaction
Free energy
Reactants
Products
Amount of energy released (Δ G < 0)
Amount of energy required (Δ G > 0)
Energy
Energy
Products
Reactants Free energy
(a) Exergonic reaction: energy released, spontaneous
(b) Endergonic reaction: energy required, nonspontaneous
▼ Figure 8.6 Free energy changes (Δ G ) in exergonic and endergonic reactions.
*The word maximum qualifies this statement, because some of the free en- ergy is released as heat and cannot do work. Therefore, ΔG represents a theo- retical upper limit of available energy.
Δ G < 0 Δ G = 0
▲ Figure 8.7 Equilibrium and work in an isolated hydroelectric system. Water flowing downhill turns a turbine that drives a genera- tor providing electricity to a lightbulb, but only until the system reaches equilibrium.
148 U n i t t w o The Cell
their metabolic pathways never reach equilibrium and can continue to do the work of life. Stepping back to look at the big picture, we can see once again how important it is to think of organisms as open systems. Sunlight provides a daily source of free energy for an ecosystem’s plants and other photosynthetic organisms. Animals and other nonphotosynthetic organisms in an eco- system must have a source of free energy in the form of the organic products of photosynthesis. Now that we have ap- plied the free-energy concept to metabolism, we are ready to see how a cell actually performs the work of life.
equilibrium if they occurred in the isolation of a test tube. Because systems at equilibrium are at a minimum of G and can do no work, a cell that has reached metabolic equilib- rium is dead! The fact that metabolism as a whole is never at equilibrium is one of the defining features of life. Like most systems, a living cell is not in equilibrium. The constant flow of materials in and out of the cell keeps the metabolic pathways from ever reaching equilibrium, and the cell continues to do work throughout its life. This prin- ciple is illustrated by the open (and more realistic) hydro- electric system in (^) Figure 8.8a. However, unlike this simple system in which water flowing downhill turns a single turbine, a catabolic pathway in a cell releases free energy in a series of reactions. An example is cellular respiration, illustrated by analogy in Figure 8.8b. Some of the revers- ible reactions of respiration are constantly “pulled” in one direction—that is, they are kept out of equilibrium. The key to maintaining this lack of equilibrium is that the product of a reaction does not accumulate but instead becomes a re- actant in the next step; finally, waste products are expelled from the cell. The overall sequence of reactions is kept going by the huge free-energy difference between glucose and oxygen at the top of the energy “hill” and carbon di- oxide and water at the “downhill” end. As long as our cells have a steady supply of glucose or other fuels and oxygen and are able to expel waste products to the surroundings,
Δ G < 0
Δ G < 0
Δ G < 0
Δ G < 0
(a)
(b) A multistep open hydroelectric system. Cellular respiration is analogous to this system: Glucose is broken down in a series of exergonic reactions that power the work of the cell. The product of each reaction is used as the reactant for the next, so no reaction reaches equilibrium.
An open hydroelectric system. Water flowing through a turbine keeps driving the generator because intake and outflow of water keep the system from reaching equilibrium.
▲ Figure 8.8 Equilibrium and work in open systems.
C o n C e p t C h e C K 8. 2
- Cellular respiration uses glucose and oxygen, which have high levels of free energy, and releases Co 2 and water, which have low levels of free energy. is cellular respiration spontaneous or not? is it exergonic or endergonic? what happens to the energy released from glucose?
- how would the processes of catabolism and anabolism relate to Figure 8.5c?
- w h a t i F? some nighttime partygoers wear glow-in- the-dark necklaces. the necklaces start glowing once they are “activated” by snapping the necklace in a way that allows two chemicals to react and emit light in the form of chemiluminescence. is the chemical reaction ex- ergonic or endergonic? explain your answer. For suggested answers, see appendix a.
C O N C E P T 8.
ATP powers cellular work by coupling
exergonic reactions to endergonic
reactions
A cell does three main kinds of work:
- Chemical work, the pushing of endergonic reactions that would not occur spontaneously, such as the synthesis of polymers from monomers (chemical work will be dis- cussed further here and in Chapters 9 and 10)
- Transport work, the pumping of substances across mem- branes against the direction of spontaneous movement (see Chapter 7)
- Mechanical work, such as the beating of cilia (see Chapter 6), the contraction of muscle cells, and the movement of chromosomes during cellular reproduction A key feature in the way cells manage their energy re- sources to do this work is energy coupling , the use of an exergonic process to drive an endergonic one. ATP is re- sponsible for mediating most energy coupling in cells, and in most cases it acts as the immediate source of energy that powers cellular work.
150 U n i t t w o The Cell
(less stable) than the original unphosphorylated molecule (Figure 8.10). Transport and mechanical work in the cell are also nearly always powered by the hydrolysis of ATP. In these cases, ATP hydrolysis leads to a change in a protein’s shape and often its ability to bind another molecule. Sometimes this occurs via a phosphorylated intermediate, as seen for the transport protein in Figure 8.11a. In most instances of mechanical work involving motor proteins “walking” along
P
P (^) i
(^1) P (^) i 2
Glutamic acid Ammonia
Δ G Glu = +3.4 kcal/mol
Δ G Glu = +3.4 kcal/mol
Δ G Glu = +3.4 kcal/mol
Net Δ G = –3.9 kcal/mol
Δ G ATP = –7.3 kcal/mol
ATP + ADP^ + ADP^ +
ATP
Glu Glutamine
Glu
NH 3
Glu +^ NH^3 +
NH 2
NH 3
Glutamic acid Phosphorylated intermediate
Glu Glu Glutamine
Glu
NH (^2)
GluNH^2 + ADP^ +
1 2
(a) Glutamic acid conversion to glutamine. Glutamine synthesis from glutamic acid (Glu) by itself is endergonic (Δ G is positive), so it is not spontaneous.
(b) Conversion reaction coupled with ATP hydrolysis. In the cell, glutamine synthesis occurs in two steps, coupled by a phosphorylated intermediate. ATP phos- phorylates glutamic acid, making it less stable. Ammonia displaces the phosphate group, forming glutamine.
(c) Free-energy change for coupled reaction. Δ G for the glutamic acid conversion to glutamine (+3.4 kcal/mol) plus Δ G for ATP hydrolysis (–7.3 kcal/mol) gives the free-energy change for the overall reaction (–3.9 kcal/mol). Because the overall process is exergonic (net Δ G is negative), it occurs spontaneously.
▲ Figure 8.10 How ATP drives chemical work: Energy coupling using ATP hydrolysis. In this example, the exergonic process of ATP hydrolysis is used to drive an endergonic process— the cellular synthesis of the amino acid glutamine from glutamic acid and ammonia.
m a k e c o n n e c t i o n s Referring to Figure 5.14, explain why glutamine (Gln) is diagrammed as a glutamic acid (Glu) with an amino group attached.
Motor protein
ATP (^) ATP
Transport protein Solute Vesicle Cytoskeletal track
Solute transported
P (^) i
ADP + P (^) i ATP^ ADP + P (^) i
P
(a) Transport work: ATP phosphorylates transport proteins. (b) Mechanical work: ATP binds noncovalently to motor proteins and then is hydrolyzed.
Protein and vesicle moved
▲ Figure 8.11 How ATP drives transport and mechanical work. ATP hydrolysis causes changes in the shapes and binding affinities of proteins. This can occur either (a) directly, by phosphorylation, as shown for a membrane protein carrying out active transport of a solute (see also Figure 7.15), or (b) indirectly, via noncovalent binding of ATP and its hydrolytic products, as is the case for motor proteins that move vesicles (and other organelles) along cytoskeletal “tracks” in the cell (see also Figure 6.21).
cytoskeletal elements (Figure 8.11b), a cycle occurs in which ATP is first bound noncovalently to the motor protein. Next, ATP is hydrolyzed, releasing ADP and (^) ~P (^) i. Another ATP molecule can then bind. At each stage, the motor pro- tein changes its shape and ability to bind the cytoskeleton, resulting in movement of the protein along the cytoskeletal track. Phosphorylation and dephosphorylation promote crucial protein shape changes during many other important cellular processes as well.
C h a p t e r 8 An Introduction to Metabolism 151
The Regeneration of ATP An organism at work uses ATP continuously, but ATP is a renewable resource that can be regenerated by the addition of phosphate to ADP (Figure 8.12). The free energy required to phosphorylate ADP comes from exergonic breakdown reactions (catabolism) in the cell. This shuttling of inorganic phosphate and energy is called the ATP cycle, and it couples the cell’s energy-yielding (exergonic) processes to the energy- consuming (endergonic) ones. The ATP cycle proceeds at an astonishing pace. For example, a working muscle cell recycles its entire pool of ATP in less than a minute. That turnover represents 10 million molecules of ATP consumed and re- generated per second per cell. If ATP could not be regener- ated by the phosphorylation of ADP, humans would use up nearly their body weight in ATP each day. Because both directions of a reversible process cannot be downhill, the regeneration of ATP is necessarily endergonic: ADP + (^) ~P (^) i S ATP + H 2 O ΔG = +7.3 kcal/mol (+30.5 kJ/mol) (standard conditions) Since ATP formation from ADP and (^) ~P (^) i is not spontane- ous, free energy must be spent to make it occur. Catabolic (exergonic) pathways, especially cellular respiration, pro- vide the energy for the endergonic process of making ATP. Plants also use light energy to produce ATP. Thus, the ATP cycle is a revolving door through which energy passes dur- ing its transfer from catabolic to anabolic pathways.
ATP synthesis from ADP + requires energy.
ATP hydrolysis to ADP + yields energy.
Energy for cellular work (endergonic, energy-consuming processes)
Energy from catabolism (exergonic, energy-releasing processes)
ADP +
ATP +^ H 2 O
P (^) i
P (^) i
P (^) i
▲ Figure 8.12 The ATP cycle. Energy released by breakdown reac- tions (catabolism) in the cell is used to phosphorylate ADP, regenerat- ing ATP. Chemical potential energy stored in ATP drives most cellular work.
C o n C e p t C h e C K 8. 3
- how does atp typically transfer energy from exergonic to endergonic reactions in the cell?
- which of the following has more free energy: glutamic
acid + ammonia + atp or glutamine + aDp + ~p i? explain
your answer.
- m a k e c o n n e c t i o n s Does Figure 8.11a show passive or active transport? explain. (see Concepts 7.3 and 7.4.) For suggested answers, see appendix a.
C O N C E P T 8.
Enzymes speed up metabolic reactions
by lowering energy barriers
The laws of thermodynamics tell us what will and will not happen under given conditions but say nothing about the rate of these processes. A spontaneous chemical reaction oc- curs without any requirement for outside energy, but it may occur so slowly that it is imperceptible. For example, even though the hydrolysis of sucrose (table sugar) to glucose and fructose is exergonic, occurring spontaneously with a release of free energy (ΔG = - 7 kcal/mol), a solution of sucrose dis- solved in sterile water will sit for years at room temperature with no appreciable hydrolysis. However, if we add a small amount of the enzyme sucrase to the solution, then all the sucrose may be hydrolyzed within seconds, as shown below:
Sucrose (C 12 H22 O 11 )
Glucose (C 6 H 12 O 6 )
Fructose (C 6 H 12 O 6 )
O H^2 O OH HO
Sucrase
How does the enzyme do this? An enzyme is a macromolecule that acts as a catalyst , a chemical agent that speeds up a reaction without being consumed by the reaction. In this chapter, we are focusing on enzymes that are proteins. (Some RNA molecules, called ribozymes, can function as enzymes; these will be discussed in Chapters 17 and 25.) Without regulation by enzymes, chemical traffic through the pathways of metabolism would become terribly congested because many chemical reactions would take such a long time. In the next two sections, we will see why spontaneous reactions can be slow and how an enzyme changes the situation.
The Activation Energy Barrier Every chemical reaction between molecules involves both bond breaking and bond forming. For example, the hydro- lysis of sucrose involves breaking the bond between glucose and fructose and one of the bonds of a water molecule and then forming two new bonds, as shown above. Changing one molecule into another generally involves contorting the start- ing molecule into a highly unstable state before the reaction can proceed. This contortion can be compared to the bend- ing of a metal key ring when you pry it open to add a new key. The key ring is highly unstable in its opened form but returns to a stable state once the key is threaded all the way onto the ring. To reach the contorted state where bonds can change, reactant molecules must absorb energy from their surround- ings. When the new bonds of the product molecules form, energy is released as heat, and the molecules return to stable shapes with lower energy than the contorted state.
C h a p t e r 8 An Introduction to Metabolism 153
substrate to the product (or products) of the reaction. The overall process can be summarized as follows: Enzyme + Enzyme- Enzyme + Substrate(s) ∆ substrate ∆ Product(s) complex For example, the enzyme sucrase (most enzyme names end in
- ase) catalyzes the hydrolysis of the disaccharide sucrose into its two monosaccharides, glucose and fructose (see p. 151): Sucrase + Sucrase- Sucrase + Sucrose + ∆ sucrose-H 2 O ∆ Glucose + H2 O complex Fructose The reaction catalyzed by each enzyme is very specific; an enzyme can recognize its specific substrate even among closely related compounds. For instance, sucrase will act only on sucrose and will not bind to other disaccharides, such as maltose. What accounts for this molecular recogni- tion? Recall that most enzymes are proteins, and proteins are macromolecules with unique three-dimensional config- urations. The specificity of an enzyme results from its shape, which is a consequence of its amino acid sequence. Only a restricted region of the enzyme molecule actually binds to the substrate. This region, called the active site , is typically a pocket or groove on the surface of the enzyme where catalysis occurs (^) (Figure 8.15a). Usually, the active site is formed by only a few of the enzyme’s amino acids, with the rest of the protein molecule providing a framework that determines the shape of the active site. The specificity of an enzyme is attributed to a complementary fit between the shape of its active site and the shape of the substrate. An enzyme is not a stiff structure locked into a given shape. In fact, recent work by biochemists has shown clearly that enzymes (and other proteins as well) seem to “dance” between subtly different shapes in a dynamic equilibrium, with slight differ- ences in free energy for each “pose.” The shape that best fits the substrate isn’t necessarily the one with the low- est energy, but during the very short time the enzyme takes on this shape, its active site can bind to the substrate. It has been known for more than 50 years that the active site itself is also not a rigid receptacle for the substrate. As the substrate enters the active site, the enzyme changes shape slightly due to interactions between the substrate’s chemical groups and chemical groups on the side chains of the amino acids that form the active site. This shape change makes the active site fit even more snugly around the substrate (Figure 8.15b). The process is like
reaction exergonic. Enzymes can only hasten reactions that would eventually occur anyway, but this enables the cell to have a dynamic metabolism, routing chemicals smoothly through metabolic pathways. Also, enzymes are very specific for the reactions they catalyze, so they determine which chem- ical processes will be going on in the cell at any given time.
Substrate Specificity of Enzymes
The reactant an enzyme acts on is referred to as the en- zyme’s substrate. The enzyme binds to its substrate (or sub- strates, when there are two or more reactants), forming an enzyme-substrate complex. While enzyme and substrate are joined, the catalytic action of the enzyme converts the
Free energy
Progress of the reaction
Reactants
Products
Δ G is unaffected by enzyme
E (^) A without enzyme
Course of reaction without enzyme EA with enzyme is lower
Course of reaction with enzyme
▲ Figure 8.14 The effect of an enzyme on activation energy. Without affecting the free-energy change (Δ G ) for a reaction, an en- zyme speeds the reaction by reducing its activation energy (EA).
(a)
Substrate
Active site
Enzyme-substrate complex
Enzyme
In this space-filling model of the enzyme hexokinase (blue), the active site forms a groove on the surface. The enzyme’s substrate is glucose (red).
(b) When the substrate enters the active site, it forms weak bonds with the enzyme, inducing a change in the shape of the protein. This change allows additional weak bonds to form, causing the active site to enfold the substrate and hold it in place.
▲ Figure 8.15 Induced fit between an enzyme and its substrate.
154 U n i t t w o The Cell
brief covalent bonding between the substrate and the side chain of an amino acid of the enzyme. Subsequent steps of the reaction restore the side chains to their original states, so that the active site is the same after the reaction as it was before. The rate at which a particular amount of enzyme converts substrate to product is partly a function of the initial concen- tration of the substrate: The more substrate molecules that are available, the more frequently they access the active sites of the enzyme molecules. However, there is a limit to how fast the reaction can be pushed by adding more substrate to a fixed concentration of enzyme. At some point, the concen- tration of substrate will be high enough that all enzyme mol- ecules have their active sites engaged. As soon as the product exits an active site, another substrate molecule enters. At this substrate concentration, the enzyme is said to be saturated, and the rate of the reaction is determined by the speed at which the active site converts substrate to product. When an enzyme population is saturated, the only way to increase the rate of product formation is to add more enzyme. Cells often increase the rate of a reaction by producing more enzyme molecules. You can graph the overall progress of an enzy- matic reaction in the scientific skills exercise.
a clasping handshake, with binding between enzyme and substrate becoming tighter after the initial contact. This so-called induced fit brings chemical groups of the active site into positions that enhance their ability to catalyze the chemical reaction.
Catalysis in the Enzyme’s Active Site
In most enzymatic reactions, the substrate is held in the active site by so-called weak interactions, such as hydro- gen bonds and ionic bonds. R groups of a few of the amino acids that make up the active site catalyze the conversion of substrate to product, and the product departs from the ac- tive site. The enzyme is then free to take another substrate molecule into its active site. The entire cycle happens so fast that a single enzyme molecule typically acts on about a thousand substrate molecules per second, and some en- zymes are even faster. Enzymes, like other catalysts, emerge from the reaction in their original form. Therefore, very small amounts of enzyme can have a huge metabolic im- pact by functioning over and over again in catalytic cycles. Figure 8.16 shows a catalytic cycle involving two substrates and two products. Most metabolic reactions are reversible, and an enzyme can catalyze either the forward or the reverse reaction, de- pending on which direction has a negative ΔG. This in turn depends mainly on the relative concentrations of reactants and products. The net effect is always in the direction of equilibrium. Enzymes use a variety of mechanisms that lower activation energy and speed up a reaction (see Figure 8.16, step^3 ):
- When there are two or more reactants, the active site provides a template on which the substrates can come together in the proper orientation for a reaction to occur between them.
- As the active site of an enzyme clutches the bound sub- strates, the enzyme may stretch the substrate molecules toward their transition-state form, stressing and bending critical chemical bonds that must be broken during the reaction. Because EA is proportional to the difficulty of breaking the bonds, distorting the substrate helps it ap- proach the transition state and thus reduces the amount of free energy that must be absorbed to achieve that state.
- The active site may also provide a microenvironment that is more conducive to a particular type of reaction than the solution itself would be without the enzyme. For example, if the active site has amino acids with acidic R groups, the active site may be a pocket of low pH in an otherwise neutral cell. In such cases, an acidic amino acid may facilitate H+^ transfer to the substrate as a key step in catalyzing the reaction.
- Amino acids in the active site directly participate in the chemical reaction. Sometimes this process even involves
Enzyme-substrate complex
Enzyme
Products
4 Products are released.
4
Active site is available for two new substrate molecules.
5
Substrates
2
Substrates are converted to products.
3
Substrates are held in active site by weak interactions, such as hydrogen bonds and ionic bonds.
1 Substrates enter active site; enzyme changes shape such that its active site enfolds the substrates (induced fit).
▲ Figure 8.16 The active site and catalytic cycle of an enzyme. An enzyme can convert one or more reactant molecules to one or more product molecules. The enzyme shown here converts two sub- strate molecules to two product molecules. D r a w i t The enzyme-substrate complex passes through a transition state (see Figure 8.13). Label the part of the cycle where the transition state occurs.
156 U n i t t w o The Cell
Enzyme Inhibitors
Certain chemicals selectively inhibit the action of specific enzymes. Sometimes, the inhibitor attaches to the enzyme by covalent bonds, in which case the inhibition is usually irreversible. Many enzyme inhibitors, however, bind to the enzyme by weak interactions, and when this occurs the inhi- bition is reversible. Some reversible inhibitors resemble the normal substrate molecule and compete for admission into the active site (^) (Figure 8.18a and b). These mimics, called competitive inhibitors , reduce the productivity of enzymes by blocking substrates from entering active sites. This kind of inhibition can be overcome by increasing the concentra- tion of substrate so that as active sites become available, more substrate molecules than inhibitor molecules are around to gain entry to the sites. In contrast, noncompetitive inhibitors do not directly compete with the substrate to bind to the enzyme at the active site (^) (Figure 8.18c). Instead, they impede enzymatic reactions by binding to another part of the enzyme. This interaction causes the enzyme molecule to change its shape
Just as each enzyme has an optimal temperature, it also has a pH at which it is most active. The optimal pH values for most enzymes fall in the range of pH 6–8, but there are exceptions. For example, pepsin, a digestive enzyme in the human stomach, works best at pH 2. Such an acidic envi- ronment denatures most enzymes, but pepsin is adapted to maintain its functional three-dimensional structure in the acidic environment of the stomach. In contrast, trypsin, a digestive enzyme residing in the alkaline environment of the human intestine, has an optimal pH of 8 and would be dena- tured in the stomach (Figure 8.17b).
Cofactors
Many enzymes require nonprotein helpers for catalytic activity. These adjuncts, called cofactors , may be bound tightly to the enzyme as permanent residents, or they may bind loosely and reversibly along with the substrate. The cofactors of some enzymes are inorganic, such as the metal atoms zinc, iron, and copper in ionic form. If the cofactor is an organic molecule, it is referred to, more specifically, as a coenzyme. Most vitamins are important in nutrition because they act as coenzymes or raw materials from which coenzymes are made.
pH
0 1 2 3 4 5 6 7 8 9 10
20 40 60 80 100 120
(a) Optimal temperature for two enzymes
(b) Optimal pH for two enzymes
Temperature (°C)
Optimal pH for pepsin (stomach enzyme)
Optimal pH for trypsin (intestinal enzyme)
Optimal temperature for typical human enzyme (37°C)
Optimal temperature for enzyme of thermophilic (heat-tolerant) bacteria (77°C)
0
Rate of reaction
Rate of reaction
▲ Figure 8.17 Environmental factors affecting enzyme activ- ity. Each enzyme has an optimal (a) temperature and (b) pH that favor the most active shape of the protein molecule.
D r a w i t Given that a mature lysosome has an internal pH of around 4.5, draw a curve in (b) showing what you would predict for a lysosomal enzyme, labeling its optimal pH.
(a) Normal binding
(b) Competitive inhibition
(c) Noncompetitive inhibition
Substrate Active site
Enzyme
Competitive inhibitor
Noncompetitive inhibitor
A substrate can bind normally to the active site of an enzyme.
A competitive inhibitor mimics the substrate, competing for the active site.
A noncompetitive inhibitor binds to the enzyme away from the active site, altering the shape of the enzyme so that even if the substrate can bind, the active site functions less effectively, if it all.
▼ Figure 8.18 Inhibition of enzyme activity.
C h a p t e r 8 An Introduction to Metabolism 157
in such a way that the active site becomes less effective at catalyzing the conversion of substrate to product. Toxins and poisons are often irreversible enzyme inhibi- tors. An example is sarin, a nerve gas. Sarin was released by terrorists in the Tokyo subway in 1995, causing the death of several people and injury to many others. This small molecule binds covalently to the R group on the amino acid serine, which is found in the active site of acetylcholines- terase, an enzyme important in the nervous system. Other examples include the pesticides DDT and parathion, inhibi- tors of key enzymes in the nervous system. Finally, many antibiotics are inhibitors of specific enzymes in bacteria. For instance, penicillin blocks the active site of an enzyme that many bacteria use to make their cell walls.
The Evolution of Enzymes
e v o l u t i o n (^) Thus far, biochemists have discovered and named more than 4,000 different enzymes in various spe- cies, most likely a very small fraction of all enzymes. How did this grand profusion of enzymes arise? Recall that most enzymes are proteins, and proteins are encoded by genes. A permanent change in a gene, known as a mutation, can result in a protein with one or more changed amino acids. In the case of an enzyme, if the changed amino acids are in the active site or some other crucial region, the altered en- zyme might have a novel activity or might bind to a different substrate. Under environmental conditions where the new function benefits the organism, natural selection would tend to favor the mutated form of the gene, causing it to persist in the population. This simplified model is generally accepted as the main way in which the multitude of different enzymes arose over the past few billion years of life’s history. Data supporting this model have been collected by re- searchers using a lab procedure that mimics evolution in natural populations. One group tested whether the function of an enzyme called β-galactosidase could change over time in populations of the bacterium Escherichia coli (E. coli). β-galactosidase breaks down the disaccharide lactose into the simple sugars glucose and galactose. Using molecular techniques, the researchers introduced random mutations into E. coli genes and then tested the bacteria for their abil- ity to break down a slightly different disaccharide (one that has the sugar fucose in place of galactose). At the end of the experiment, the “evolved” enzyme bound the new substrate several hundred times more strongly, and broke it down 10 to 20 times more quickly, than did the original enzyme. The researchers found that six amino acids had changed in the enzyme altered in this experiment. Two of these changed amino acids were in the active site, two were nearby, and two were on the surface of the protein (^) (Figure 8.19). This experiment and others like it strengthen the notion that a few changes can indeed alter enzyme function.
Two changed amino acids were found near the active site.
Active site
Two changed amino acids were found in the active site.
Two changed amino acids were found on the surface. ▲ Figure 8.19 Mimicking evolution of an enzyme with a new function. After seven rounds of mutation and selection in a lab, the enzyme β-galactosidase evolved into an enzyme specialized for break- ing down a sugar different from lactose. This ribbon model shows one subunit of the altered enzyme; six amino acids were different.
C o n C e p t C h e C K 8. 4
- Many spontaneous reactions occur very slowly. why don’t all spontaneous reactions occur instantly?
- why do enzymes act only on very specific substrates?
- w h a t i F? Malonate is an inhibitor of the enzyme succinate dehydrogenase. how would you determine whether malonate is a competitive or noncompetitive inhibitor?
- m a k e c o n n e c t i o n s in nature, what conditions could lead to natural selection favoring bacteria with enzymes that could break down the fucose-containing disaccharide discussed above? see the discussion of natural selection in Concept 1.2. For suggested answers, see appendix a.
C O N C E P T 8.
Regulation of enzyme activity helps
control metabolism
Chemical chaos would result if all of a cell’s metabolic pathways were operating simultaneously. Intrinsic to life’s processes is a cell’s ability to tightly regulate its metabolic pathways by controlling when and where its various en- zymes are active. It does this either by switching on and off the genes that encode specific enzymes (as we will discuss in Unit Three) or, as we discuss here, by regulating the activity of enzymes once they are made.
Allosteric Regulation of Enzymes In many cases, the molecules that naturally regulate en- zyme activity in a cell behave something like reversible
C h a p t e r 8 An Introduction to Metabolism 159
Localization of Enzymes Within the Cell The cell is not just a bag of chemicals with thousands of dif- ferent kinds of enzymes and substrates in a random mix. The cell is compartmentalized, and cellular structures help bring order to metabolic pathways. In some cases, a team of enzymes for several steps of a metabolic pathway are as- sembled into a multienzyme complex. The arrangement facilitates the sequence of reactions, with the product from the first enzyme becoming the substrate for an adjacent enzyme in the complex, and so on, until the end product is released. Some enzymes and enzyme complexes have fixed locations within the cell and act as structural components of particular membranes. Others are in solution within par- ticular membrane-enclosed eukaryotic organelles, each with its own internal chemical environment. For example, in eu- karyotic cells, the enzymes for cellular respiration reside in specific locations within mitochondria (Figure 8.22). In this chapter, you have learned that metabolism, the intersecting set of chemical pathways characteristic of life, is a choreographed interplay of thousands of different kinds of cellular molecules. In the next chapter, we will explore cellular respiration, the major catabolic pathway that breaks down organic molecules, releasing energy that can be used for the crucial processes of life.
the affinity for oxygen of the remaining binding sites. Thus, where oxygen is at high levels, such as in the lungs or gills, hemoglobin’s affinity for oxygen increases as more binding sites are filled. In oxygen-deprived tissues, however, the re- lease of each oxygen molecule decreases the oxygen affinity of the other binding sites, resulting in the release of oxygen where it is most needed. Cooperativity works similarly in multisubunit enzymes that have been studied.
Feedback Inhibition
When ATP allosterically inhibits an enzyme in an ATP- generating pathway, the result is feedback inhibition, a com- mon mode of metabolic control. In feedback inhibition , a metabolic pathway is halted by the inhibitory binding of its end product to an enzyme that acts early in the path- way. Figure 8.21 shows an example of feedback inhibition operating on an anabolic pathway. Some cells use this five- step pathway to synthesize the amino acid isoleucine from threonine, another amino acid. As isoleucine accumulates, it slows down its own synthesis by allosterically inhibiting the enzyme for the first step of the pathway. Feedback inhibition thereby prevents the cell from making more isoleucine than is necessary and thus wasting chemical resources.
Active site available; pathway can proceed
Isoleucine used up by cell
Isoleucine binds to allosteric site.
Initial substrate (threonine)
Threonine in active site
Enzyme 1 (threonine deaminase)
Active site of enzyme 1 is no longer able to cata- lyze the conversion of threonine to interme- diate A; pathway is halted.
End product (isoleucine)
Intermediate A
Intermediate B
Enzyme 2
Intermediate C
Enzyme 3
Enzyme 4
Intermediate D
Enzyme 5
Feedback inhibition
▲ Figure 8.21 Feedback inhibition in isoleucine synthesis.
Mitochondria
1
μm
The matrix contains enzymes in solution that are involved in one stage of cellular respiration. Enzymes for another stage of cellular respiration are embedded in the inner membrane. ▲ Figure 8.22 Organelles and structural order in metabolism. Organelles such as the mitochondrion (TEM) contain enzymes that carry out specific functions, in this case cellular respiration.
C o n C e p t C h e C K 8. 5
- how do an activator and an inhibitor have different ef- fects on an allosterically regulated enzyme?
- regulation of isoleucine synthesis is an example of feedback inhibition of an anabolic pathway. with that in mind, explain how atp might be involved in feedback inhibition of a catabolic pathway. For suggested answers, see appendix a.
160 U n i t t w o The Cell
protein phosphorylation) also causes changes in the shape and binding affinities of transport and motor proteins.
- Catabolic pathways drive regeneration of ATP from ADP + (^) ~P (^) i. ? (^) Describe the ATP cycle: How is ATP used and regenerated in a cell?
C O N C E P T 8.
Enzymes speed up metabolic reactions by lowering energy
barriers (pp. 151–157)
- In a chemical reaction, the energy necessary to break the bonds of the reactants is the activation energy , EA.
- Enzymes lower the EA barrier:
SuMMAry OF KEy COnCEPTS
C O N C E P T 8.
An organism’s metabolism transforms matter and energy,
subject to the laws of thermodynamics (pp. 142–145)
- Metabolism is the collection of chemical reactions that occur in an organism. Enzymes catalyze reactions in intersecting metabolic pathways , which may be catabolic (breaking down molecules, releasing energy) or anabolic (building molecules, consuming energy).
- Energy is the capacity to cause change; some forms of energy do work by moving matter. Kinetic energy is associated with motion and includes thermal energy associated with random motion of atoms or molecules. Heat is thermal energy in trans- fer from one object to another. Potential energy is related to the location or structure of matter and includes chemical energy possessed by a molecule due to its structure.
- The first law of thermodynamics , conservation of energy, states that energy cannot be created or destroyed, only trans- ferred or transformed. The second law of thermodynamics states that spontaneous processes , those requiring no outside input of energy, increase the entropy (disorder) of the universe. ? Explain how the highly ordered structure of a cell does not conflict with the second law of thermodynamics.
C O N C E P T 8.
The free-energy change of a reaction tells us whether or not
the reaction occurs spontaneously (pp. 145–148)
- A living system’s free energy is energy that can do work under cellular conditions. The change in free energy (ΔG) during a bio- logical process is related directly to enthalpy change (ΔH) and to the change in entropy (ΔS): ΔG = ΔH - TΔS. Organisms live at the expense of free energy. A spontaneous process occurs with no energy input; during such a process, free energy decreases and the stability of a system increases. At maximum stability, the system is at equilibrium and can do no work.
- In an exergonic (spontaneous) chemical reaction, the products have less free energy than the reactants (-ΔG). Endergonic (nonspontaneous) reactions require an input of energy (+ΔG). The addition of starting materials and the removal of end prod- ucts prevent metabolism from reaching equilibrium. ? Explain the meaning of each component in the equation for the change in free energy of a spontaneous chemical reaction. Why are spontaneous reactions important in the metabolism of a cell?
C O N C E P T 8.
ATP powers cellular work by coupling exergonic reactions to
endergonic reactions (pp. 148–151)
- ATP is the cell’s energy shuttle. Hydrolysis of its terminal phos- phate yields ADP and (^) ~P (^) i and releases free energy.
- Through energy coupling , the exergonic process of ATP hydro- lysis drives endergonic reactions by transfer of a phosphate group to specific reactants, forming a phosphorylated inter- mediate that is more reactive. ATP hydrolysis (sometimes with
8 Chapter Review
Free energy
Progress of the reaction
Reactants
Products
Δ G is unaffected by enzyme
E (^) A without enzyme
Course of reaction without enzyme EA with enzyme is lower
Course of reaction with enzyme
- Each enzyme has a unique active site that binds one or more substrate(s) , the reactants on which it acts. It then changes shape, binding the substrate(s) more tightly ( induced fit ).
- The active site can lower an EA barrier by orienting substrates correctly, straining their bonds, providing a favorable microenvi- ronment, or even covalently bonding with the substrate.
- Each enzyme has an optimal temperature and pH. Inhibitors reduce enzyme function. A competitive inhibitor binds to the active site, whereas a noncompetitive inhibitor binds to a dif- ferent site on the enzyme.
- Natural selection, acting on organisms with variant enzymes, is responsible for the diversity of enzymes found in organisms. ? (^) How do both activation energy barriers and enzymes help maintain the structural and metabolic order of life?
C O N C E P T 8.
Regulation of enzyme activity helps control metabolism
(pp. 157–159)
- Many enzymes are subject to allosteric regulation : Regulatory molecules, either activators or inhibitors, bind to specific regu- latory sites, affecting the shape and function of the enzyme. In cooperativity , binding of one substrate molecule can stimulate binding or activity at other active sites. In feedback inhibition , the end product of a metabolic pathway allosterically inhibits the enzyme for a previous step in the pathway.
- Some enzymes are grouped into complexes, some are incorpo- rated into membranes, and some are contained inside organ- elles, increasing the efficiency of metabolic processes. ? (^) What roles do allosteric regulation and feedback inhibition play in the metabolism of a cell?
