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

(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)] [basic energy concepts (T. Paustian’s Microbiology Textbook)] [index]

METABOLISM

(3) 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

(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)] [types of catabolic pathways (T. Paustian’s Microbiology Textbook)] [index]

(5) 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)]

(c) [anabolism, anabolic steroids (Google Search)] [anabolism, summary of anabolism (T. Paustian’s Microbiology Textbook)] [index]

(6) 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 6.7, Disequilibrium and work in close and open systems

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

ENERGY

(7) 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)

(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

(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 6.5: 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 6.7, 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

(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 6.5: 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

(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

(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)

(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) = adnosine + 1 phosphate

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

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

(d) See figure 6.8, 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 6.10: The ATP cycle

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

(18) ATP catabolism (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 6.8, 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 6.9, Energy coupling by phosphate transfer

ENERGY OF ACTIVATION

(21) Activation energy (transition state)

(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 6.12, 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

(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 6.12, 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 hydrophoblic 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

(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 6.13, 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

(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

(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)

(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

(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 6.14, The induced fit between an enzyme and its substrate

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

(29) 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 6.11, Example of an enzyme-catalyzed reaction: Hydrolysis of sucrose

(c) See Figure 6.15, 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

(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 6.16, Environmental factors affecting enzymes

ENZYME ACCESSORIES

(34) Cofactors

(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

(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

(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

(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 6.17, Inhibition of Enzyme Activity (b)

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

(38) Noncompetitive inhibitors

(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 6.17, Inhibition of Enzyme Activity (c)

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

(39) Allosteric inhibitors

(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 6.18 Allosteric regulation of enzyme activity

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

(40) Activators

(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 6.18 Allosteric regulation of enzyme activity

(41) 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 6.20, Cooperativity

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

(42) 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 6.19, Feedback inhibition

(h) See Figure 1.8, 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 6.21, 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 phosphage 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 monosacharide 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 anitparallel 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