An Introduction to Metabolism

Important words and concepts from Chapter 6, Campbell & Reece, 2002 (1/14/2005):

by Stephen T. Abedon (abedon.1@osu.edu) for Biology 113 at the Ohio State University

Course-external links are in brackets

Click [index] to access site index

Click here to access text's website

Vocabulary words are found below

(1) Chapter title: An Introduction to Metabolism

(a) Found at this site are additional pages of possibly related interest including: [biochemistry] [enzymes]

(b) [an introduction to metabolism (Google Search)] [reactions and enzymes (Online Biology Book)] [index]

(2) Bioenergetics (see also bioenergetics)

(a) Bioenergetics is "The study of how organisms manage their energy resources."

(b) That is, bioenergetics is the study of how energy moves through and is employed by organisms

(c) (note that apparently bioenergetics has become some kind of New Age therapy -- and with a name like that, is it any wonder? -- but this makes it very difficult to find meaningful links to pages that deal with the science of bioenergetics via searches for that term)

(d) [bioenergetics (Google Search)] [index]

METABOLISM

(3) Metabolism (see also metabolism)

(a) Metabolism is the sum of all of the chemical reactions that occur within an organism

(b) Metabolism = catabolism + anabolism

(c) [metabolism (Google Search)] [anabolic and catabolic pathways (simple, nicely done figure giving overview of integration of catabolism with metabolism) (BSC Courseware)] [index]

(4) Catabolism (see also catabolism)

(a) Catabolic reactions are those metabolic reactions

(i) That yield energy (are involved in the "generation" of cellularly-useful energy)

(ii) Are involved in the breaking down of more-complex molecules to simpler ones

(b) [catabolism (Google Search)] [index]

(5) Anabolism (see also anabolism)

(a) Anabolism is that aspect of metabolism involved in the net use of energy to build more-complex molecules and structures from simpler ones

(b) The root of the word is the same as that employed in the phrase "anabolic steroids" which are steroid drugs employed to "build up" the body, especially in terms of increasing muscle mass [questions and answers about anabolic steroids (NIDA Notes)]

(6) Energy coupling (see also energy coupling)

(a) Anabolism and catabolism are intimately linked (and thereby is all of metabolism) by energy coupling

(b) Energy coupling means that the energy "generated" by catabolic processes is harnessed by cells to perform anabolic processes

(c) "The metabolic pathways intersect in such a way that energy released from the 'downhill' reactions of catabolism can be used to drive the 'uphill' reactions of the anabolic pathways. This transfer of energy from catabolism to anabolism is called energy coupling."

(d) See Figure, Disequilibrium and work in close and open systems

(e) [energy coupling and metabolism (Google Search)] [index]

ENERGY

(7) Energy (see also energy)

(a) Energy is found in various forms

(b) Potential energy is energy that is stored in some manner

(d) Organisms are energy transducers, entities that transform energy from one form into another

(e) For example, energy flows through organisms from the energy of photons to the potential energy found in chemical bonds, and ultimately to the less-useful energy of heat

(a) FAQ: What do you mean by "Energy in bonds"? When electrons are locked into chemical bonds, there is a certain amount of energy associated with those electrons. This is the (chemically available) energy that exists within, for example, the food you eat. Recall that the farther an electron is from the atomic nucleus, the more energy it contains. This distance from an atomic nucleus can be locked into an electron when that electron is locked into a chemical bond. Indeed, one can think of the energy required to drive forward the endergonic dehydration synthesis reaction as energy that becomes trapped in chemical bonds and associated with electrons that are now farther from atomic nuclei than they otherwise might be (in fact, were). Finally, note that all else held constant, an electron that is shared between two atoms possessing relatively equal electronegativity will be trapped at a further distance from the two atomic nuclei than an atom locked between two atoms having dissimilar electronegativities. For example, an electron found between H and O will be much closer to an atomic nuclei (i.e., that of O) than an electron found between C and C, or even O and O.

(f) [energy metabolism (Google Search)] [index]

(8) Thermodynamics (first law of thermodynamics, second law of thermodynamics) (see also thermodynamics, first law of thermodynamics, and second law of thermodynamics)

(a) First law of thermodynamics

(i) Energy can be neither created nor destroyed

(ii) Energy "generated" in any system is instead energy that has been transformed from one state to another (e.g., from chemically stored energy to heat)

(b) Second law

(i) The efficiencies of energy transformation can never equal 100%

(ii) Consequently, all processes lose energy, typically as heat, and therefore are not reversible unless this energy lost may be supplied from the environment

(iii) For chemical reactions that are easily reversed at ambient temperatures, the energy required for the reversal is simply low enough that it can be supplied by the heat of the environment (e.g., the dissociation of water H₂O <==> OH^- + H⁺ is driven in both directions by heat)

(iv) "In performing various kinds of work, living cells unavoidably convert organized forms of energy to heat . . . In machines and organisms, even energy that performs useful work is eventually converted to heat . . . Conversion to heat is the (ultimate) fate of . . . chemical energy."

(c) [thermodynamics, thermodynamics first law, thermodynamics second law, thermodynamics third law (Google Search)] [index]

(9) Organisms are energy transducers (see also energy transduction)

(a) Organisms are transducers of energy (and thereby are less than 100% efficient) who employ the energy they've harnessed to grow, repair, and maintain their bodies, compete with other organisms, and to produce new organisms (babies)

(b) In the process of doing these things, organisms generate waste chemicals and heat

(c) Organisms create local regions of order at the expense of using up some fraction of the total supply of useful energy found in the universe (but don't fret too much, the energy would have been used up anyway)

(d) [energy transduction (Google Search)] [index]

EQUILIBRIUM CHEMISTRY

(10) Chemical disequilibrium

(a) Left to itself, any system will degrade to its most stable state

(b) For an organism this state represents chemical equilibrium

(d) The chemistry of life is one in which energy is obtained from the environment and employed to prevent the attainment of chemical equilibrium

(e) Viable organisms exist in a chemical disequilibrium that is maintained via the harnessing of energy obtained from the organism's environment (e.g., you eat to live)

(f) See Figure: The relationship of free energy to stability, work capacity, and spontaneous change

(g) [chemical disequilibrium (Google Search)] [index]

(11) Harnessing movement toward chemical equilibrium

(a) Catabolic processes represent a chemical movement toward equilibrium

(b) Movement toward equilibrium occurs spontaneously

(d) See Figure, Disequilibrium and work in close and open systems

(e) [movement toward chemical equilibrium (Google Search)] [index]

(12) Harnessing energy to move toward chemical disequilibrium

(a) Anabolic processes represent chemical movement away from equilibrium

(b) Movement away from equilibrium does not occur spontaneously

(d) [movement away from chemical equilibrium (Google Search)] [index]

(13) Coupling movement toward chemical equilibrium and disequilibrium

(a) Energy coupling within organisms represents the linkage of anabolic processes with catabolic processes so that the inevitable tendencies toward chemical equilibrium may be harnessed to drive other aspects of cells away from chemical equilibrium

(b) In other words, the food you eat is driven, for the most part, down a path toward chemical equilibrium so that the energy found in that food may be harnessed to build up and maintain the chemical disequilibrium of your living body

(c) (in terms of the waterfall analogy for energy, catabolism is the movement of water over the falls -- See Figure 6.2: Transformations between kinetic and potential energy; anabolism is the energy-requiring movement of water back up to the reservoir above the falls, and reactions that are spontaneously reversible under physiological conditions are equivalent to the waterfall spray that floats on a breeze back to the waterfall above -- OK, the latter analogy is a little forced but not too terrible especially if the waterfall is very short and the flow over it very slow such that the random movement of water molecules either in the air or within the water results in movement upstream as well as down; if you coupled the waterfall to a turbine, then you would have a coupling between catabolism and anabolism, but of course no turbine/pump is 100% efficient so at least some volume of water runs over the falls whose associated-energy is lost to the environment as heat rather than captured by the turbine -- See Figure 6.7, Disequilibrium and work in close and open systems)

GIBBS FREE ENERGY

(14) Exergonic reaction (see also exergonic reaction)

(a) An exergonic reaction net-generates (gives off) energy (e.g., heat)

(b) That is, the products of such a reaction possess less stored energy than do the reactants

(d) Exergonic reactions move reactants in the direction of chemical equilibrium (or, in some cases and more-easily visualized, towards physical equilibrium with exergonic processes that are not chemical reactions)

(e) See Figure: The relationship of free energy to stability, work capacity, and spontaneous change

(f) Approximate synonyms of exergonic include

(i) Decrease in free energy (-DG)

(ii) Increase in stability

(iii) Spontaneous

(iv) Downhill

(v) Movement towards equilibrium

(vi) ATP producing

(vii) Catabolism

(g) (remember exergonic as in explosion, a very spontaneous reaction)

(h) [exergonic, exergonic reaction, exergonic reactions (Google Search)] [index]

(15) Endergonic reaction (see also endergonic reaction)

(a) An endergonic reaction is one that requires a net input of energy in order to proceed

(b) The products of endergonic reactions possess more energy than do the reactants

(d) Endergonic reactions (or processes) move away from chemical equilibrium

(e) (remember endergonic as in energy must be put into the system to drive it forward)

(f) Approximate synonyms of endergonic include

(i) Increase in free energy (+DG)

(ii) Decrease in stability

(iii) Non-spontaneous

(iv) Uphill

(v) Movement away from equilibrium

(vi) ATP requiring

(vii) Anabolism

(g) FAQ: Exergonic, exothermic, and spontaneity? To those of you who are having troubling dealing with the terms exergonic and endergonic because you learned these concepts in chemistry class using the terms exothermic and endothermic, here's an attempt at a clarification. I follow this with a restatement of activation energy and why it is that all reactions can have an activation energy, regardless of whether those reactions are endergonic or exergonic. First, the various terms are not quite synonymous (i.e., neither exergonic and exothermic are synonymous nor endergonic and endothermic). However, if you find it easier to think of them as synonymous, then go for it. The goal is to get across the concept of how some reactions require a net input of energy in order to go forward (endergonic and, often, endothermic) while others net give off energy (exergonic and, also typically, exothermic). Note that the -thermic terms tend to be limited to describing heat energy while the -gonic terms are broader, referring to free energy. That is, two possible things can drive a reaction spontaneously forward: A release of energy as reactants go to products or an increase in entropy as reactants go to products. The -thermic terms more or less only deal with the former while the -gonic terms consider both. Second, keep in mind that even exergonic reactions will require some input of energy. That is, the exergonic term does not mean no input of energy. Instead it means that the reactions net generate energy. In other words, when you sum together input energy and output energy, exergonic reactions will have produced more energy than they have consumed. The initial input of energy is called activation energy. See figure 6.9 of your text where the curve first rises (indicating a requirement for an input of energy, i.e., activation energy) then drops as this exergonic reaction goes to completion. If the drop results in the (free) energy associated with the products being less (i.e., the curve is lower) than that associated with reactants, then it is an exergonic reaction. If the drop results in the (free) energy associated with the products being more than that associated with the reactants, then it is an endergonic reaction, and clearly some net amount of energy must have been pumped into the system: what you ended with has more energy associated with it than what you started with! Finally, keep in mind that the term "spontaneous" does not mean, in a chemical sense, that a reaction will happen fast. For a chemical reaction to happen at all, it must either be spontaneous or energy must be supplied to drive the reaction forward. The rate at which a reaction goes forward, however, depends on the amount of activation energy necessary to initiate the reaction. If a lot of activation energy is required, then the reaction will tend to not go forward (all else held constant). If little activation energy is required, then the reaction will tend to go forward very readily. These are difficult concepts. In some ways understanding them too well may be counter-productive to your understanding of biology at this level. Just keep in mind that some reactions require a net input of (free) energy to be driven forward, while other reactions net give off some amount of (free) energy as they go forward, but all reactions require some input of (free) energy (activation energy) before they can go forward.

(h) [endergonic, endergonic reaction, endergonic reactions (Google Search)] [index]

ENERGY COUPLING

(16) Coupling endergonic and exergonic reactions (see also energy coupling)

(a) In organisms, endergonic and exergonic reactions are coupled

(b) That is, those reactions that give off a net amount of energy are used to drive forward those reactions that absorb a net amount of energy

(17) Adenosine triphosphate (ATP) (AMP, ADP) (see also ATP)

(a) Endergonic and exergonic reactions (anabolism and catabolism) are linked by an energy storage molecule called adenosine triphosphate (ATP)

(b) ATP is a nucleoside, which is a nucleic acid lacking a phosphate group (this way they can name ATP in a way that indicates the number of phosphates explicitly, i.e.,

(i) adenosine = no phosphates

(ii) adenosine monophosphate (AMP) = adenosine + 1 phosphate

(iii) adenosine diphosphate (ADP) = adenosine + 2 phosphates

(iv) adenosine triphosphate (ATP) = adenosine + 3 phosphates)

(d) See Figure, The structure and hydrolysis of ATP

(e) The most-common reaction in which ATP liberates energy to power anabolic processes is ATP hydrolysis

(f) See Figure: The ATP cycle

(g) [ATP, adenosine triphosphate (Google Search)] [index]

(18) ATP catabolism (ATP hydrolysis) (see also ATP hydrolysis)

(a) The following reaction is ATP hydrolysis:

(i) ATP + H₂O + activation energy à ADP + P_i + energy

(b) Note that this reaction releases energy (i.e., it is exergonic) which is true in general for hydrolysis reactions (i.e., hydrolysis is an example of a catabolic reaction)

(d) [ATP catabolism, ATP hydrolysis (Google Search)] [index]

(19) ATP is a product of catabolism

(a) The reverse reaction of ATP hydrolysis, that which generates ATP from ADP -- i.e., ADP + P_i + energy à ATP + H₂O -- is the dominant useful product of catabolic reactions

(b) Note that this reaction requires energy (i.e., it is endergonic) which is true in general for dehydration synthesis (i.e., dehydration synthesis is an example of an anabolic reaction)

(c) (The catabolic processes that drive the production of ATP -- either directly or indirectly -- include glycolysis, the Krebs cycle, and chemiosmosis which your text covers in chapter 9)

(d) [ATP synthesis (Google Search)] [chemistry of ATP synthesis (heavy-duty chemistry) (Metabolic Pathways in Biochemistry)] [index]

(20) How ATP works

(a) ATP is often said to possess high-energy bonds

(b) In fact, what ATP possesses are relatively low energy bonds, but ones that are readily broken (i.e., ATP hydrolysis has a low energy of activation) and the breaking of those bonds (i.e., ATP hydrolysis) supplies enough energy to power the individual steps of most anabolic reactions

(c) See Figure, The structure and hydrolysis of ATP

(d) One reason for ATP's instability has to do with the high charge density of all of the linked phosphates

(e) Enzymes are employed to harness the energy released by the loss of a phosphate from ATP to do specific, energy-requiring (endergonic) tasks

(f) See Figure, Energy coupling by phosphate transfer

ENERGY OF ACTIVATION

(21) Activation energy (transition state) (see also activation energy)

(a) The hydrolysis of ATP to form ADP is an example of a spontaneous reaction that readily proceeds (ADP = adenosine diphosphate)

(b) Not all spontaneous reactions (i.e., exergonic reactions) readily occur

(c) This is because most reactions, including ATP hydrolysis, require an input of energy before a chemical reaction will proceed, even if the chemical reaction ultimately gives back more energy than it receives (any reaction that does not require such an input of activation energy has, in fact, already occurred -- right?)

(d) See Figure, An energy profile of an exergonic reaction

(e) The energy that must be added to reactants to initiate a reaction is known as activation energy

(f) Think of activation energy as being that energy that is necessary to push the reactant(s) into a structure that is intermediate (a.k.a., the transition state) between the structure of the reactants and that of the products

(g) [activation energy (Google Search)] [index]

(22) Heat energy (see also waste heat)

(a) In most of the reactions you are used to observing, heat supplies the energy of activation

(b) That is, the random jostling that heat represents will, from time to time, successfully jostle reactants into a state resembling products, thus allowing the reaction to proceed

(c) See Figure, An energy profile of an exergonic reaction

(d) This is a very inefficient process since it occurs by random interactions between molecules

(e) To make the process go faster by adding more heat, this inefficiency is not overcome; instead increasing temperature increases the total number (and intensity) of interactions, thus increasing the total number jostlings that leads to the formation of products

(23) Low temperature stability

(a) The requirement for heat to drive many reactions forward (by supplying the activation energy) explains why the components of organisms are relatively stable: the breakdown of most biological molecules requires sufficient activation energy that it does not occur or occurs only rarely at normal body temperatures

(b) This requirement for heat activation of chemical reactions also explains why high temperatures can be very damaging to living things: heat drives the activation of many spontaneous reactions that essentially degrade the body molecule by molecule (i.e., towards equilibrium), but these reactions either do not occur or occur only very slowly at normal body temperatures

(c) FAQ: Low temperature stability, could you explain? (i) Chemical stability results from most chemical reactions requiring a significant input of energy before they can proceed. All reactions that require this energy input are so unstable they have probably already occurred! Without that input of energy, reactions don't start, so therefore they don't occur. If reactants are not converted to products, then we might say that the reactants are stable under the existing conditions. In non-catalyzed reactions, the only way to speed up a reaction is to supply heat (or some other form of energy). The heat supplies the activation energy. Speeding up the reaction means that it happens faster. Slowing down the reaction means that it happens more slowly. If heat is used to speed up a reaction, then removing heat should slow down the reaction. If you remove enough heat, you will slow the reaction down to essentially nil. Heat is proportional to temperature. Thus, it is possible to lower temperatures sufficiently far that a given reaction does not occur. We would therefore describe the reactants as being stable at that temperature. All living forms of life exist at a temperature that is low enough that its biomolecules exist in a relatively stable state. Thus, we can owe the existence of organisms to the requirement for activation energy to effect the degradation of biomolecules. So long as temperatures are sufficiently low, then these biomolecules don't degrade, i.e., they exist stably at these relatively low temperatures.

(d) FAQ: Low temperature stability, could you explain? (ii) The temperature stability of lipids can be described in similar terms (i.e., above) except that it is not covalent bonds that are being broken. Instead, it is weaker bonds that occur between hydrophobic molecules. The number of these bonds is proportional to how closely the two hydrophobic molecules can pack together. The more closely together they can pack, the more bonds. The more bonds, the more temperature stability (i.e., the more heat required to separate the molecules from each other). Double bonds in fatty acids put kinks in these fatty acids. Kinks inhibit close packing between the two fatty acids. Consequently, kinks lower higher-temperature stability. Why have them then? Because they simultaneously increase lower-temperature fluidity.

Stability (supplemental discussion)

· To be unstable, something must have the potential to change into something else that possesses less free energy (i.e., potential to change to lower free energy state or substance).

· To be unstable, releasing something's ability to change into something else must be relatively easy (i.e., requiring little energy).

· Stability = low free energy

· Stability = high activation energy

· Something can be high in free energy but still quite stable: high activation energy can be almost as good an indicator of high stability as low free-energy content

ENZYMES

(24) Enzymes (see also enzyme)

(a) Enzymes are organic catalysts generally consisting of proteins

(b) Catalysts are molecules that speed up reactions by lowering energies of activation

(c) Particularly, what catalysts do is to more-efficiently direct heat energy (or other sources of energy such as ATP) so that reactants are much more likely to be driven to a transition state, for a given input of energy, than they would were processes driven only by random interactions between molecules

(d) See Figure, Enzymes lower the barrier of activation energy

(e) Furthermore, catalysts are not used up in the course of a reaction, but instead may be reused again and again

(f) By using enzymes, cells control when, where, and how fast the chemical reactions that are useful to the cell will proceed

(g) This control forms the basis of how living things maintain their highly organized (and liquid) complexity

(h) [enzymes (Google Search)] [index]

(25) Substrate (see also substrate)

(a) The reactants acted upon by an enzyme are called a substrates

(b) A typical enzyme-catalyzed chemical reaction may be summarized by the following outline:

enzyme

substrate(s) ------------------------> product(s)

(c) Depending on the enzyme/reaction, enzyme-mediated reactions may be reversible or not reversible, just as some not-catalyzed reactions are reversible whereas other not-catalyzed reactions are not reversible

(d) [enzyme substrate (Google Search)] [index]

(26) Enzyme specificity (see also enzyme specificity and specificity)

(a) Enzymes are capable of distinguishing between typically even closely related compounds

(b) That is, most enzymes will act on one substrate but not necessarily on structurally closely related substrates

(d) [enzyme specificity (Google Search)] [index]

ACTIVE SITE

(27) Active site (catalytic site) (see also active site)

(a) An enzyme's active site is a pocket or groove that indents into the hydrophilic surface of an enzyme

(b) The active site is where the substrate binds and catalysis occurs

(d) Typically only a few amino acids directly serve to define the active site

(e) These amino acids that are found in the active site are not necessarily located adjacently in the protein's primary structure (that is, only through the complex folding of the protein do amino acids become located adjacent within the active site)

(f) The rest, not active site portion of the protein serves to:

(i) Maintain the conformation (e.g., stability) of the active site

(ii) Effect various means of control over the active site

(iii) Attaches the enzyme to other molecules

(g) [enzyme active site (Google Search)] [index]

(28) Induced fit (see also induced fit)

(a) Enzyme specificity occurs as a consequence of the compatibility of the fit between substrate(s) and active site

(b) Active sites are not rigid complements of substrate structure, however

(c) Instead, active sites are capable of responding to the presence of the substrate by changing shape (i.e., the physical state of active sites as well as proteins is more liquid phase than solid phase)

(d) By changing shape the active site may initially take on a conformation that is conducive to the diffusion of the substrate(s) into the active site

(e) Once the substrate has diffused into the active site, the active site then takes on a conformation that actively binds the substrate(s) in place

(f) This change in enzyme/active site conformation in response to the presence of a substrate is called induced fit

(g) See Figure, The induced fit between an enzyme and its substrate

(h) [induced fit enzyme (Google Search)] [index]

(29) Enzyme-substrate complex (see also enzyme-substrate complex)

(a) The complex formed between the enzyme's active site and the substrate(s) is called an enzyme-substrate complex

(b) Typically weak bonds hold together enzyme-substrate complexes (e.g., hydrogen bonds, ionic bonds -- that is, the interaction between enzymes and substrates is an important example of the fluid nature of life at the level of molecular interactions)

(c) The bonds between the substrate and enzyme more-specifically are between the substrate and the amino-acid R groups defining the active site

(d) [enzyme-substrate complex (Google Search)] [index]

ENZYME CATALYSIS

(30) Enzyme-mediated catalysis, overview

(a) Below is an overview of enzyme-mediated catalysis; notice how dependent all of the steps are on life's literally fluid nature

(b) See Figure, Example of an enzyme-catalyzed reaction: Hydrolysis of sucrose

(c) See Figure, The catalytic cycle of an enzyme

(d) Substrate(s) diffuse from the surrounding medium into the active site

(e) The presence of the correct substrate(s) in the active site induces the active site to change conformation such that the substrate(s) are now actively bound

(f) The change in conformation also causes the R groups of active-site amino acids to interact with the substrate such that the active site fits the transition state better than it fits the substrate

(g) The subsequently induced strain corresponds to the energy of activation that is indirectly supplied by heat in not-catalyzed reactions

(h) This subtle and highly directed straining of the substrate(s) is one of things responsible for the ability of enzymes to lower activation energies ("distorting the substrate reduces the amount of thermal energy that must be absorbed in order to achieve a transition state"), i.e., by applying energy just where it is needed, much energy can be saved (basically this is the same premise that is behind the use of space heaters to keep one room or one area of a house particularly warm)

(i) Once activation energy has been thusly supplied, the reaction can continue on to form the product(s)

(j) The conformation of the enzyme following catalysis is then such that the product(s) does not strongly bind, allowing the product to diffuse away

(k) The enzyme is now ready to receive another substrate(s) molecule(s)

(l) When product(s) concentrations are high relative to substrate(s) concentrations, however, enzymes often can reverse these steps resulting in the catalysis of the reverse reaction (if any such reaction is thermodynamically plausible)

(31) Additional mechanisms of catalysis

(a) The chemical mechanisms enzymes employ to catalyze reactions are numerous and include (and are not necessarily mutually exclusive):

(i) Active sites can bind two or more substrates in proper orientations so that new bonds between substrates can form

(ii) Active sites can stress the substrate into the transition state

(iii) Active sites can maintain conducive physical environments (e.g., pH)

(iv) Active sites can participate directly in the reaction (e.g., forming transient covalent bonds with substrates)

(v) Active sites can carry out a sequence of manipulations in a defined temporal order (e.g., step A à step B à step C)

ENZYME KINETICS

(32) Enzyme saturation (see also enzyme saturation and saturation)

(a) Enzymes can very rapidly turn over (i.e., catalytically act upon) substrate (thousands of times per second = thousands of substrate molecules per second)

(b) When substrate-to-enzyme concentrations are sufficiently high, substrate can diffuse into active sites faster than enzymes can catalyze substrates

(d) Only at this point is the rate of a reaction dependent on the speed of the enzyme

(e) Otherwise the rate of reactions are predominantly dependent on substrate concentrations (and, for reversible reactions, product concentrations as well)

(f) "When an enzyme population is saturated, the only way to increase productivity is to add more enzyme. Cells sometimes do this by making more enzyme molecules."

(g) [enzyme saturation (Google Search)] [index]

(33) Physical effects on enzyme activity (enzyme activity)

(a) If we saturate an enzyme with substrate (i.e., high substrate concentration per unit enzyme), we can measure enzyme activity, which is basically the speed, or turnover rate, seen when the enzyme's rate of activity is not limited by substrate availability

(b) Various changes to an enzyme's environment can modify this activity

(c) Particularly, enzymes have activities that are optimized for certain ranges of physical and chemical parameters, very typically which are nearly exactly those ranges of physical and chemical parameters in which the enzyme's function evolved

(d) See Figure, Environmental factors affecting enzymes

ENZYME ACCESSORIES

(34) Cofactors (see also cofactor)

(a) Cofactors are non-protein, non-substrate adjuncts required for protein activity and often directly involved in active site chemistry, i.e., they are different from molecules that serve simply as enzyme activators

(b) Cofactors may be organic or inorganic (e.g., metal atoms such as zinc, iron, copper, etc.)

(d) [enzyme cofactor, enzyme cofactors (Google Search)] [index]

(35) Coenzyme (see also coenzyme)

(a) If organic, a cofactor is called a coenzyme

(b) Many of the vitamins you need in your diet are used as or modified to be coenzymes

(36) Inhibitors (see also enzyme inhibitor)

(a) Certain substances can function to inhibit enzyme activity

(b) Typically this inhibition occurs only following the binding of the inhibitor (in some manner) to some specific location on the enzyme

(d) ("Irreversible inhibition occurs only rarely in vivo, but there are a few important cases of which you should be aware. Usually these are cases of poisoning. [For example,] Cyanide is found in the seeds of some fruits and can react with the metal ions found in some enzymes.")

(e) [enzyme inhibitor, enzyme inhibitors (Google Search)] [index]

CONTROL OF ENZYME ACTIVITY

(37) Competitive inhibitors (see also competitive inhibition)

(a) Competitive inhibitors bind directly to the active sites of the enzyme whose function they are inhibiting

(b) These are competitive in the sense that they are reversibly bound and that with sufficient concentrations substrates can "compete" for access to the active site, thereby displacing, at least temporarily, the competitive inhibitor

(c) Thus, competitive inhibition may be overcome by increasing concentration of substrate that is in contact with the inhibited enzyme

(d) See Figure, Inhibition of Enzyme Activity (b)

(e) [competitive inhibition, competitive inhibitor, competitive inhibitors (Google Search)] [index]

(38) Noncompetitive inhibitors (see also competitive inhibition)

(a) Noncompetitive inhibitors bind enzymes other than at the enzyme's active site

(b) Noncompetitive inhibitors cannot be competed off of enzymes by increasing substrate concentrations (because the inhibitor and the substrate bind at different locations on the enzyme)

(c) See Figure, Inhibition of Enzyme Activity (c)

(d) [noncompetitive inhibition, noncompetitive inhibitor, noncompetitive inhibitors (Google Search)][index]

(39) Allosteric inhibitors (see also allosteric inhibition)

(a) Allosteric inhibitors are noncompetitive inhibitors that are capable of inhibiting the proper functioning of the active sites of enzyme subunits in addition to the active site found in the subunit to which the inhibitor is bound

(b) For example, assume that an enzyme consists of otherwise identical subunits A, B, C, and D; an allosteric inhibitor may bind to A and that binding is sufficient to inhibit the activity of not just A but of B, C, and D as well

(c) See Figure Allosteric regulation of enzyme activity

(d) [allosteric inhibition, allosteric inhibitor, allosteric inhibitors (Google Search)] [allosteric enzyme inhibition (Natural Toxins Research Initiative)][index]

(40) Activators (see also enzyme activator)

(a) In addition to inhibitors, there exist molecules, called activators, that are capable of stabilizing or enhancing enzyme activity by binding to sites other than the active site

(b) See Figure Allosteric regulation of enzyme activity

(41) Cooperativity (see also cooperativity)

(a) In some cases the binding of substrate to one subunit of an enzyme can increase the activity of adjacent subunits on the same enzyme

(b) In this case the substrate is essentially acting as an "allosteric" activator of the other subunits

(c) Hemoglobin's binding to oxygen is a classic example of this cooperativity between enzyme subunits (hemoglobin's job is not exactly enzymatic, however, since this protein serves as the reusable oxygen carrier molecule found in the blood rather than serving as a chemical catalyst, though one could argue that the reaction catalyzed by hemoglobin is the reversible binding of molecular oxygen)

(d) See Figure, Cooperativity

(e) [enzyme cooperativity (Google Search)] [index]

(42) Feedback inhibition (see also feedback inhibition)

(a) Biological systems do their best to avoid wasting either time or materials

(b) One way biological systems accomplish this avoidance is by controlling the activity of enzymes

(d) Basically the product of an enzyme or series of enzymes (pathway) will serve to negatively regulate the enzyme or pathway

(e) That is, when end product is sufficiently plentiful, the end product will significantly inhibit at least one enzyme of a series responsible for making that end product

(f) Ideally the enzyme blocked will be the first enzyme on a pathway that is dedicated to making that end product and only that end product (i.e., the point of commitment to making a given end product)

(g) See Figure, Feedback inhibition

(h) See Figure, Regulation by feedback inhibition

(i) [feedback inhibition (Google Search)] [index]

(43) Enzyme localization

(a) Biological systems can also minimize waste by possessing efficient physical structure

(b) That is, cells are more than just bags of water solution, they are more organized, possessing greater structure than that

(d) For example, enzymes that supply substrates to other enzymes will be located very closely together

(e) Enzymes also are often located within the same structure, e.g., as components of giant enzyme complexes or within the same membrane-enclosed structure

(f) Substrate and enzyme concentrations can also be maintained at high levels by maintaining enzymes and substrates within small volumes

(g) Thus, cell structure contributes (often dramatically) to metabolic function (indeed, tissue and organ structure, e.g., the stomach, can perform similar functions at macroscopic scales)

(h) See Figure, Organelles and structural order in metabolism

GLYCOLYSIS PREVIEW

(44) (if there is time, we will go over glycolysis as an example of enzyme mediated metabolism)

QUESTION RE: FIRST MIDTERM EXAM

(45) FAQ: If it's not too much trouble, would you please advise the specific molecules for which you want us to know how to draw (or recognize) their structures?

(a) I believe the comprehensive answer to that question is:

(i) Glucose (including carbon numbering)

(ii) ribose (including carbon numbering plus where the phosphate and the nitrogenous bases are attached--though not the latter structures)

(iii) Deoxyribose

(iv) An amino acid

(v) The various functional groups as discussed in your text

(vi) The oxidation of carbon, particularly from the perspective of what functional groups are attached as carbon becomes increasingly oxidized

(vii) Be able to recognize a steroid/cholesterol

(viii) The difference between a starch (e.g., amylose) and cellulose. And don't forget about branches in starches

(ix) The difference between a ketose and an aldose

(x) The difference between a hexose and various other carbon-numbered sugars

(xi) The difference between a ring form and a linear form of a monosaccharide

(xii) The difference between a monosaccharide and a disaccharide and a polysaccharide

(xiii) A peptide bond

(xiv) A structural vs. geometric isomer vs. enantiomers (and/or stereoisomers--I don't make much of a big deal of the difference)

(xv) A chiral carbon vs. a non-chiral carbon

(xvi) A hydrocarbon vs. a non-hydrocarbon

(xvii) Dehydration synthesis vs. hydrolysis, including the involvement of energy

(xviii) What is a fat, and how is a fat formed?

(xix) What is a phospholipid?

(xx) The structure of water

(xxi) The structure of a hydrogen bond

(xxii) A non-polar covalent bond

(xxiii) A polar covalent bond

(xxiv) An ionic bond

(xxv) You probably should also have some sense of what a phosphodiester linkage is as well as glycosidic linkage

(xxvi) Don't forget about the antiparallel nature of the double helix, or the sugar-phosphate backbone

(xxvii) Don't forget what inorganic phosphate looks like

(xxviii) What is a cis double bond vs. a trans double bond?

(xxix) What do unsaturated vs. saturated fatty acids look like?

(xxx) Is guanine a purine, or is it a pyrimidine? Ditto, Adenine, thymine, and cytosine

(xxxi) What does a water molecule in ice look like

(b) Basically, you are responsible for what I lectured on, in particular what is found in the online lecture notes. No, you do not need to know the structures of the nitrogenous bases, the amino acid R groups, or the exact structure of cholesterol...

(c) I hope that isn't too overwhelming. There is a lot of material to learn in biology, even if presented in a simplified form. By all means ask any additional questions that you may have, and I'll see you on Tuesday to answer additional questions.

VOCABULARY

(46) Vocabulary [index]

(a) Activation energy

(b) Activators

(d) Additional mechanisms of catalysis

(e) Adenosine triphosphate

(f) Allosteric inhibitors

(g) Anabolism

(h) ATP

(i) ATP catabolism

(j) ATP hydrolysis

(k) ATP is a product of catabolism

(l) Bioenergetics

(m) Catabolism

(n) Chemical disequilibrium

(o) Coenzyme

(p) Cofactors

(q) Competitive inhibitors

(r) Cooperativity

(s) Coupling endergonic and exergonic reactions

(t) Coupling movement toward chemical equilibrium and disequilibrium

(u) Endergonic reaction

(v) Energy

(w) Energy coupling

(x) Enzymes

(y) Enzyme localization

(z) Enzyme-mediated catalysis

(aa) Enzyme saturation

(bb) Enzyme specificity

(cc) Enzyme-substrate complex

(dd) Exergonic reaction

(ee) Feedback inhibition

(ff) First law of thermodynamics

(gg) Harnessing energy to move toward chemical disequilibrium

(hh) Harnessing movement toward chemical equilibrium

(ii) Heat energy

(jj) How ATP works

(kk) Induced fit

(ll) Inhibitors

(mm) Low temperature stability

(nn) Metabolism

(oo) Noncompetitive inhibitors

(pp) Organisms are energy transducers

(qq) Physical effects on enzyme activity

(rr) Second law of thermodynamics

(ss) Substrate

(tt) Thermodynamics

(47) Practice questions [index]

(a) Describe in simple terms how the second law of thermodynamics impacts on biological systems.

(b) Cells harness chemical reactions that are moving toward equilibrium to do what? (note: neither catabolism nor exergonic nor their ilk are answers)

(d) Give an example of a specific exergonic chemical reaction that is particularly biologically useful, in part because it requires only a low energy of activation. You do not need to show all atoms or bonds (i.e., abbreviations are acceptable) but do name all chemical players.

(e) Name a type of bond that typically binds substrates to enzyme active sites.

(f) What does the concept of "induced fit" mean?

(g) A molecule which can bind to a region of an enzyme other than the active site and which can serve to stabilize or enhance enzyme activity is called a(n) __________.

(h) In terms of reaction energetics, how do enzymes speed up biochemical reactions. (To answer this question, think in terms of energy profiles with and without catalysis.)

(i) The weak bonds which hold a substrate within an active site are typically between the substrate and what structures associated with the amino acids making up the enzyme molecule?

(j) Catabolism + __________ = Metabolism.

(k) According to the second law of thermodynamics, energy transformations can never be 100% efficient. That means that energy is lost every time its form is changed. To what form of energy is the lost energy typically lost to?

(l) To perturb a system (any system) away from equilibrium, __________ (general term) must typically be added to the system

(m) The exergonic reaction which most typically is harnessed to power endergonic reactions in biological systems is what? (show the chemical equation)

(n) The reason that spontaneous reactions do not all immediately occur is a consequence of a requirement for __________ to start a reaction going. This requirement is typically lowered by enzymes, thus explaining, in general terms, their ability to catalyze biological reactions.

(o) The reactants in enzymatically-catalyzed reactions are described by a different general term (i.e., something other than "reactant"). That term is __________.

(p) In an enzyme, name two important roles that the non-active site of the protein (i.e., the rest of the protein) performs.

(q) In an enzyme-substrate complex, the weak bonds between the enzyme's active site and substrate, that serve to hold the substrate within the active site, etc., typically are formed between the substrate and the __________ located in the active site.

(r) Enzyme saturation refers to what?

(s) Distinguish "noncompetitive enzyme inhibitor" from "competitive enzyme inhibitor".

(t) The binding of the products of an enzyme pathway to the enzymes found at the beginning of the pathway, in such as way as to prevent the use (execution) of the pathway, is termed __________.

(u) Reactions that are not catalyzed do not necessarily occur even if they are otherwise spontaneous. To go forward, such reactions require an input of energy. What typically supplies the energy (recall that we are concerned here with reactions that are not catalyzed)?

(v) Give an example of an exergonic reaction. Be sure to include all chemical players (i.e., reactants and products) and to place "energy" on the appropriate side.

(w) A pocket or groove indenting into the hydrophilic surface of an enzyme, where substrates bind and catalysis occurs, is called a(n) __________.

(x) In terms of metabolism, what is energy coupling?

(y) In terms of thermodynamic principles, why are some chemical reactions not reversible?

(z) In the chemistry of life, what is employed to prevent the attainment of chemical equilibrium?

(aa) Net movement away from chemical equilibrium

(i) Is an exergonic process

(ii) Is used to produce ATP

(iii) Does not occur spontaneously

(iv) Powers anabolic processes

(v) None of the above

(bb) Give a specific example of an endergonic reaction. Please at least show the atoms involved in the reaction (plus energy) but you may describe or name the molecules involved rather than explicitly presenting the rest of their molecular structure.

(cc) Show the chemical reaction representing ATP hydrolysis. There should be two reactants and two products, plus energy should be located on the correct side of the equation. Don't forget to indicate in the equation whether or not the reaction is reversible.

(dd) Why don't all spontaneous reactions readily occur?

(ee) What general name does one use to describe that broad class of proteins that function in metabolic processes to lower the activation energy required to initiate specific chemical reactions?

(ff) Fill in the blank:

enzyme

___________ ------------------------> product(s)

(gg) What does enzyme specificity refer to?

(hh) Describe the amino acids found in an enzyme's active site in terms of the enzyme's primary structure

(ii) Give an example of a typical type of bond (be specific) that holds together an enzyme-substrate complex.

(jj) To effect catalysis, an enzyme's __________ can stress the substrate into the transition state.

(kk) When an enzyme population is fully active and saturated with substrate, what can a cell do to further increase the rate of the reaction that is catalyzed by this enzyme?

(ll) What is a cofactor?

(mm) In general, what must an inhibitor do to impact on the activity of an enzyme?

(i) Bind to an enzyme

(ii) Bind to an enzyme's active site

(iii) Denature an enzyme

(iv) Modify an enzyme's primary structure

(v) Salt-out an enzyme

(nn) Other than by changing enzyme or inhibitor concentrations, how can competitive inhibition be overcome?

(oo) Name a property of an enzyme that must exist for that enzyme to be susceptible to allosteric inhibitors or to cooperativity. That is, in principle not all enzymes are susceptible to these effects. Why not?

(pp) Given feedback inhibition, when product is sufficiently plentiful, what happens?

(qq) In general catabolic processes break down more-complex molecules into simpler ones plus, in the course of these chemical reactions, yield __________.

(i) Adenosine diphosphate

(ii) Divalent cations

(iii) Energy

(iv) Glucose

(v) Proteins

(rr) What molecule does the body most typically employ to couple catabolism to anabolism?

(ss) Energy that is stored in some manner is generally (i.e., from physics) termed __________.

(i) Chemical energy

(ii) Metabolic energy

(iii) Potential energy

(iv) Reduced energy

(v) Stored energy

(tt) Distinguish exergonic from endergonic (being sure, as always, to convince me that you are aware of which term is associated with which description).

(uu) Which is the odd phenomenon out?

(i) ATP producing

(ii) Catabolism

(iii) Decrease in free energy (-DG)

(iv) Downhill

(v) Movement away from equilibrium

(vi) Spontaneous

(vv) ATP + __________ à ADP + Pi + energy

(ww) True or False, ATP hydrolysis has a high energy of activation.

(xx) An intermediate structure between reactants and produces is achieved via the application of __________ energy, typically supplied by heat in not-catalyzed chemical reactions.

(yy) How can a reaction be exergonic if an input of activation energy is required to initiate the reaction?

(zz) A catalyst is a molecule that __________ a reaction by lowering the __________ energy associated required to initiate a reaction.

(aaa) The ability of enzymes to distinguish between even very similar substrates is known as enzyme __________.

(bbb) In biological systems an organic catalyst that is bound to one or more reactants together are called a(n) __________.

(i) Apoenzyme

(ii) Enzymatic reaction

(iii) Enzyme-substrate complex

(iv) Lock and key

(v) Reactive enzyme

(ccc) What dose it mean for an enzyme to be saturated?

(ddd) Distinguish cofactor from coenzyme. Remember to associate terms with their definitions.

(eee) Inhibitors that reversibly bind to active sites are said to be __________ inhibitors.

(fff) __________ are substances (not reactants) capable of binding to sites other than an enzyme's active site and that binding serves to enhance (increase) an enzyme's activity.

(ggg) Give one strategy, other than producing excessively large amounts of each, that a cell might employ to maintain enzyme and substrate concentrations both at high concentrations.

(hhh) What is "Energy Coupling"?

(iii) Most potential energy in biological systems is stored within __________, such as those associated with carbohydrates, fats, and ATP.

(jjj) Energy can be neither created nor destroyed, though it may (and often is) transformed from one state to another. What, then, is the second law of thermodynamics?

(kkk) In terms of chemical equilibrium, describe the role of energy in an organism's metabolism.

(lll) In organisms such as ourselves, the energy required to move away from chemical equilibrium is harnessed from what? (no, "food" is not a sufficient answer)

(mmm) A chemical reaction that can occur spontaneously __________.

(i) Cannot exist

(ii) Is exergonic

(iii) Moves away from chemical equilibrium

(iv) Requires a net input of energy

(v) Requires an input of energy

(nnn) One of these concepts does not go with the others. Which one?

(i) Increase in free energy (+DG)

(ii) Decrease in stability

(iii) Non-spontaneous

(iv) Uphill

(v) Movement away from equilibrium

(vi) ATP producing

(vii) Anabolism

(ooo) Are dehydration synthesis reactions typically anabolic or catabolic?

(ppp) What is the relationship between activation energy and chemical stability?

(qqq) Typical properties of catalysts are that they lower energies of activation and __________.

(i) Always consist of proteins

(ii) Are not used up in reactions

(iii) Destabilize the transition state

(iv) Modify reaction spontaneities

(v) Poorly control metabolisms

(rrr) Typically a groove into the surface of a globular protein, an enzyme's site of catalysis is more typically called a(n) _________.

(sss) The non-active site portion of enzymes serves a variety of roles including maintaining the conformation (e.g., stability) of the active site, attaching the enzyme to other molecules, and __________.

(ttt) True or False, the high rigidity of an enzyme's active site gives rise to concept of induced fit.

(uuu) When substrate can diffuse into an enzyme's active site faster than an enzyme can effect catalysis, then the enzyme is maximally active and is said to be _________. Only at this point is the rate of a reaction dependent on the speed of the enzyme (i.e., on its turnover rate).

(vvv) Cofactors are not simply protein activators. What are they?

(www) Where specifically on enzymes do competitive inhibitors (but not noncompetitive inhibitors) typically bind?

(xxx) The term "Allosteric" describes

(i) Something that binds to a different subunit

(ii) Something that binds to an active site

(iii) Something that does not bind to an active site

(iv) Something that increases enzyme activity

(v) Something that is acted upon catalytically by an enzyme

(yyy) Cooperativity refers to the allosteric _________ of certain enzymes.

(zzz) In terms of enzymes, what is feedback inhibition?

(aaaa) Define "Catabolism".

(bbbb) What does "Energy Coupling" mean?

(cccc) State the First and Second laws of thermodynamics.

(dddd) Which represents the Potential Energy low, Chemical Equilibrium or Chemical Disequilibrium?

(eeee) __________ processes represent chemical movement away from equilibrium.

(ffff) Which requires a greater net input of energy, an exergonic process or an endergonic process?

(gggg) Is ATP hydrolysis endergonic or exergonic?

(hhhh) It is the requirement for __________ __________ to initiate chemical reactions that accounts for the room-temperature stability of molecules possessing high levels of free energy, such as glucose.

(iiii) When we consider enzyme-catalyzed reactions we employ a different term to describe "reactants", though we retain the term "products" for both enzyme catalyzed and not catalyzed reactions. What is this equivalent-to-"reactants" term employed when considering enzyme-catalyzed reactions?

(jjjj) The region of an enzyme at which substrates are bound to enzymes, so that the enzymes may effect catalysis, is the __________.

(kkkk) What is "Induced Fit"?

(llll) Under "Additional Mechanisms of Catalysis" I describe a number chemical mechanisms that enzymes can employ to catalyze reactions, e.g., stress substrates into the transition state. Name/describe a second.

(mmmm) When substrate is so numerous (high concentration) that substrate can diffuse into active sites faster than enzymes can catalyze the substrate, then an enzyme is said to be __________.

(nnnn) Distinguish enzyme "Cofactor" from enzyme "Coenzyme".

(oooo) Describe how a competitive inhibitor acts to inhibit enzyme-mediated catalysis, make sure that you distinguish this mechanism from that of noncompetitive inhibitors.

(pppp) In order for cooperativity to occur, an enzyme must be composed of more than one __________.

(qqqq) In feedback inhibition the product of an enzymatic pathway will serve to do what?

(rrrr) Bonus: fill in the blank and tell what this graph is describing (credit only for both correct):

(ssss) The study of how organisms manage their energy resources is called __________.

(tttt) A catabolic reaction typically is one that yields energy or __________.

(uuuu) What is energy coupling?

(vvvv) Matching: (a) first law of thermodynamics, (b) second law of thermodynamics.

(i) All processes lose energy, typically as heat: __________

(ii) Energy generated in any system is transformed from one state into another: __________

(iii) The efficiencies of energy transformation can never equal 100%: __________

(wwww) Organisms create local regions of order at the expense of using up some fraction of the total supply of useful __________ found in the universe.

(xxxx) The chemistry of life is one in which energy is obtained from the environment and employed to prevent the attainment of chemical __________.

(yyyy) Matching: (a) catabolism, (b) anabolism, (c) neither, (d) both.

(i) Exergonic: __________

(ii) Output harnessed to perform useful work: __________

(iii) Spontaneous: __________

(iv) Towards equilibrium: __________

(zzzz) What does the abbreviation "ATP" stand for?

(aaaaa) Complete the reaction: ATP + __________ + activation energy à ADP + P_i + energy

(bbbbb) The energy that must be added to reactants to initiate a reaction is known as __________.

(ccccc) True or False, increasing the temperature of reactions increases the efficiency of inter-molecular interactions (i.e., between reactants), leading to product formation occurring at a greater rate.

(ddddd) In biological systems, typically organic catalysts are described as (i.e., given the name) __________.

(eeeee) What is a substrate? (looking for definition)

(fffff) The __________ of an enzyme is where catalysis occurs.

(ggggg) The change in enzyme/active site conformation in response to the presence of a substrate is called __________.

(hhhhh) Scan (or find in PPT presentation) Figure 6.12 and have students write an essay describing the figure and what is going on.

(iiiii) The chemical mechanisms enzymes employ to catalyze reactions are numerous and include all of the following except:

(i) Active sites can bind two or more substrates in proper orientations so that new bonds between substrates can form

(ii) Active sites can increase the temperature of reactions

(iii) Active sites can maintain conducive physical environments (e.g., pH)

(iv) Active sites can participate directly in the reaction (e.g., forming transient covalent bonds with substrates)

(v) Active sites can stress the substrate into the transition state

(jjjjj) Under what circumstances is the bulk rate (i.e., that seen across the entire reaction vessel) of an enzyme-catalyzed reaction dependent solely on the speed of the enzyme?

(kkkkk) Many of the minerals you need in your diet are used as enzyme __________.

(i) Coenzymes

(ii) Cofactors

(iii) Inhibitors

(iv) Substrates

(v) None of the above

(lllll) Describe the site of binding of a non-competitive inhibitor. Yes, you can use negative terms to describe the site if you like.

(mmmmm) What is cooperativity?

(48) Practice question answers [index]

(a) biological systems must take in food (or other sources of energy) to stay alive and will tend to give off waste heat.

(b) generate ATP.

(c) Exergonic reactions are spontaneous while endergonic reactions are not spontaneous, i.e., they won't go forward without some input of energy.

(d) ATP + H₂O --> ADP + P_i + energy.

(e) ionic bond, hydrogen bond.

(f) It means that the active site is induced to take on a conformation which is complementary to that of the substrate(s) (the lock to the substrate's key) only upon exposure of the active site to a substrate(s) molecule and, furthermore, that the active site loses that substrate specific conformation following the diffusion of catalyzed substrate (i.e., product) out of the active site.

(g) activator.

(h) Enzymes serve to lower the activation energy of reactions, consequently increasing rate at which they proceed. They do this by acting specifically to stabilize the transition state rather than expending thermal motion on random efforts to achieve this stabilization.

(i) Certain amino acid R groups present in the region of the active site.

(j) Anabolism

(k) Heat

(l) Energy

(m) ATP + HOH à ADP + Pi

(n) Activation energy

(o) Substrate

(p) (i) maintains the conformation of the active site, (ii) effects various means of control over the active site, (iii) attaches the enzyme to other molecules

(q) R groups and functional groups are good answers; protein backbone is not a correct answer

(r) When substrate concentrations are so high that the rate of a reaction in a cell becomes dependent on the speed of the enzyme rather than on the concentration of substrate

(s) The former does not bind to the active site, while the latter does bind to the active site, thus excluding the substrate(s)

(t) feedback inhibition

(u) heat

(v) e.g., ATP + HOH à ADP + Pi + energy

(w) active site

(x) Energy coupling means that the energy liberated in catabolic processes is harnessed to drive forward anabolic processes

(y) A consequence of the second law of thermodynamics is that the energy lost to the environment in the course of a spontaneous chemical reaction may be in excess of that available from the environment to drive the reverse reaction forward; consequently, many reactions are not reversible and, in fact, the only reactions that are reversible are those whose free energy change going from reactants to products and then from reactants back to products is sufficiently small that it may be supplied by ambient heat

(z) Energy obtained from the environment… ultimately that energy is converted to and then used, to a large extent, as ATP

(aa) (iii) Does not occur spontaneously

(bb) This could be an example of dehydration synthesis, e.g., the synthesis of maltose from two glucose molecules: G-OH + HO-G + energy à G-O-G + H₂O where G-OH is glucose and G-O-G is maltose

(cc) ATP + H₂O à ADP + Pi + energy; the reaction is not reversible (that is, to push the reaction to the left, the reaction must be coupled to another reaction that supplies sufficient free energy to overcome the free-energy cost of phosphorylating ADP; sufficient energy to do this is not obtainable from the environment, hence the reaction is not reversible)

(dd) Even spontaneous reactions require an initial input of energy, called activation energy, to drive the reaction forward; the description spontaneous refers to the net gain in free energy that results from the reaction going to completion, not that the reaction is highly likely or that the reactants are highly unstable

(ee) Enzyme

(ff) Substrate(s)

(gg) The substrates an enzyme is capable of acting on is typically very limited; thus, only specific substrates are acted upon by a given enzyme, the enzyme is specific in what molecules it can use as substrates

(hh) The amino acids found in the active site of an enzyme are not necessarily found adjacent in terms of the enzyme's primary structure

(ii) Hydrogen bond, ionic bond, Van der Waals interactions, but not covalent bond since these are involved only in a minority of such interactions

(jj) Active site

(kk) Make more enzyme

(ll) A cofactor is a non-protein, non-substrate molecule or ion that is required by an enzyme for activity

(mm) (i) bind to an enzyme

(nn) Competitive inhibition may be overcome by increasing substrate concentration in contact with the inhibited enzyme (thus distinguishing competitive inhibition from noncompetitive inhibition)

(oo) The enzyme must have more than one subunit

(pp) With feedback inhibition, sufficiently plentiful product serves to inhibit the enzymes involved production of this product

(qq) (iii) Energy

(rr) ATP

(ss) (iii) Potential

(tt) An exergonic reaction produces more energy than it consumes such that products possess less free energy than reactants; an endergonic reaction, on the other hand, requires more energy than it produces and products possess more free energy than reactants

(uu) (vi) Movement away from equilibrium

(vv) Water

(ww) False

(xx) Activation

(yy) The chemical conversion of any reactants to products requires an input of energy (i.e., activation energy); a requirement for activation energy does not determine whether or not a reaction is exergonic; in fact, in an exergonic reaction the production of products simple results in the freeing of more energy than was required to initiate (activation energy) the reaction; for an exergonic reaction the opposite is true: the formation of the products releases less energy than the activation energy required to initiate the reaction

(zz) Speeds up; activation

(aaa) Specificity

(bbb) (iii) Enzyme-substrate complex

(ccc) It means that substrate is pouring into active site as rapidly as catalysis is occurring/product is leaving such that the overall rate of a reaction is no longer controlled by substrate concentration but instead is controlled by the inherent rate of enzyme-mediated catalysis

(ddd) A coenzyme is an organic cofactor while cofactors may be both organic or inorganic

(eee) Competitive

(fff) Activators

(ggg) Close localization of enzymes supplying substrates to subsequent enzymes along a biochemical pathway; location of enzymes within the same structure (e.g., components of the same enzyme complex); co-location within a low-volume cellular compartment such as an membrane-enclosed structure

(hhh) Energy coupling means that the energy derived from reactions that net give off energy (exergonic reactions) supply the energy to drive forward reactions that require energy (endergonic reactions)

(iii) Chemical bonds

(jjj) Second laws basically states that during the transformation of energy from one state to another the transformation cannot be 100% efficient but instead some energy always ends up no longer being available to do work

(kkk) Energy is used to drive metabolic reactions away from equilibrium

(lll) Chemical bonds, catabolic reactions, catabolism, exergonic reactions, spontaneous reactions, or ATP

(mmm) (ii) Is exergonic

(nnn) (vi) ATP producing

(ooo) Anabolic: they require energy to go forward

(ppp) The greater the activation energy, the greater the stability

(qqq) (ii) Are not used up in reactions

(rrr) Active site

(sss) Controlling the activity of the enzyme

(ttt) False

(uuu) Saturated

(vvv) Cofactors are substances typically found at enzyme active sites that are required (usually directly involved in) catalytic activity

(www) Active sites

(xxx) (iii) Something that binds to a different subunit

(yyy) Activation

(zzz) Feedback inhibition is the inhibition of enzyme activity given sufficient densities of products of the reaction catalyzed by the enzyme or by the biochemical pathway in which the enzyme participates

(aaaa) Catabolism includes those chemical reactions occurring within an organism that are energy yielding, generally taking larger substances and breaking them down into smaller ones via exergonic reactions

(bbbb) Energy coupling is the powering of endergonic reactions via the energy released from exergonic reactions; metabolically this often occurs via that synthesis of ATP via energy derived from catabolic reactions and then the powering of anabolic reactions via the hydrolysis of this ATP

(cccc) First Law: Energy can neither be created nor destroyed, only change in form. Second Law: These changes in form can never be 100% efficient.

(dddd) Chemical equilibrium

(eeee) Endergonic/anabolic

(ffff) Endergonic

(gggg) Exergonic

(hhhh) Activation energy

(iiii) Substrate

(jjjj) Active site

(kkkk) Induced fit is the modification of the shape of an enzyme's active site following the binding of substrate

(llll) E.g., modification of local pH, bringing two substrates into close proximity, participating chemically in the reaction, placing reaction steps into proper temporal sequence

(mmmm) Saturated

(nnnn) A cofactor is an organic or inorganic, non-protein molecule that modifies enzyme activity; a coenzyme is an organic cofactor

(oooo) A competitive inhibitor binds, reversibly, to the active site, thereby sterically preventing substrate binding

(pppp) Subunit/polypeptide

(qqqq) Inhibit the entire pathway, usually be inhibiting the first dedicated enzyme to that pathway

(rrrr) Bonus: substrate concentration and this is an enzyme-saturation curve

(ssss) Bioenergetics

(tttt) Decreases order, breaks down molecules from more complex to simpler forms

(uuuu) Energy coupling is the use by biological systems of the energy generated by catabolic (energy liberating) reactions to drive forward anabolic (energy requiring) reactions

(vvvv) (i) b, (ii) a, (iii) b

(wwww) Energy

(xxxx) Equilibrium

(yyyy) (i) a, (ii) a, (iii) a, (iv) a

(zzzz) Adenosine TriPhosphate

(aaaaa) H₂O

(bbbbb) Activation energy

(ccccc) False (there is no increase in efficiency)

(ddddd) Enzymes

(eeeee) A substrate is reactant in an enzyme-catalyzed reaction

(fffff) Active site

(ggggg) Induced fit

(hhhhh) Sdfsdf

(iiiii) (ii) Active sites can increase the temperature of reactions

(jjjjj) When the enzyme is saturated with substrate

(kkkkk) (ii) Cofactors

(lllll) Somewhere other than blocking the active site

(mmmmm) Cooperativity is "allosteric activation" of adjacent subunits. In particular, the activation of adjacent subunits of an enzyme when a given subunit is activated

Chapter 6, exam questions:

(#) What is the significance of enzyme localization?

A: metabolic pathways can work more efficiently if enzymes supplying substrates to the enzyme catalyzing the next reaction step are located close to each other. In this way the local concentration of the substrate around an enzyme is elevated.

(#) When the product of an enzyme or series of enzymes (i.e., a pathway) serves to negatively regulate the enzyme or pathway, this is called __________ inhibition.

A: feedback

(#) When a substrate acts as an "allosteric" activator of the other subunits of a multi-subunit enzyme, we describe this process as:

(i) Allosteric activation

(ii) Competitive activation

(iii) Cooperativity

(iv) Enzyme saturation

(v) Positive control

A: (iii) Cooperativity

(#) What is the difference between a competitive and non-competitive enzyme inhibitor?

A: A competitive inhibitor binds at an enzyme's active site and can be diluted away and/or competed away by the substrate whereas a non-competitive inhibitor does not and cannot.

(#) When substrate-to-enzyme concentrations are sufficiently high, substrate can diffuse into active sites faster than enzymes can catalyze substrate. At this point the enzyme is said to be __________.

(i) Activated

(ii) Functional

(iii) Inhibited

(iv) Localized

(v) Saturated

A: (v) Saturated

(#) In addition to stressing the substrate into the transition state, name two additional ways by which an enzyme can facilitate the catalysis of a chemical reaction.

A: binding two or more substrate molecules in proper orientation, maintaining conducive physical environment, participate directly in reactions, sequence manipulations in a defined temporal order

(#) Active sites are capable of responding to the presence of the substrate by changing shape. This is a concept known as __________ fit.

A: induced

(#) An enzyme-substrate complex forms typically via weak bonds between a substrate and an enzyme's __________.

A: Active site

(#) By using __________, cells control when, where, and how fast the chemical reactions that are useful to the cell will proceed.

A: enzymes

(#) Explain what a transition state is in terms of activation energy.

A: A transition state is a structure that is intermediate between substrate(s) and product(s) and typically this state is unstable and can be achieved only via an input of energy. This required energy for the achievement of the transition state we call activation energy.

(#) Most of the ATP found in cells is produced using energy released over the course of __________.

(i) ADP hydrolysis

(ii) Anabolic reactions

(iii) ATP hydrolysis

(iv) Catabolic reactions

(v) None of the above

A: Catabolic reactions

(#) What is an Endergonic reaction?

A: An endergonic reaction has a DG that is greater than zero (i.e., positive DG) and therefore requires a net input of energy to move forward.

(#) True or False, Catabolic processes represent a chemical movement away from equilibrium.

A: False.

(#) All processes lose energy, typically as heat, and therefore are not reversible unless this energy lost may be supplied from the environment. This inefficiency is a consequence of what is described as the _________ law of thermodynamics.

A: 2^nd.