BioChem Exam #3 15-19

The concentration of fructose-2,6-bisphosphate in a cell depends on the balance between in synthesis (catalyzed by phosphofructokinase-2) and its breakdown (catalyzed by fructose-1,6-bisphosphatase). The separate enzymes that control the formation and breakdown of fructose-2,6-bisphosphate are themselves controlled by a phosphorylation/dephosphorylation mechanism.

How can the synthesis and breakdown of fructose-2,6-bisphosphate be controlled independently?

The designation delta G knot prime indicates a biological standard state. If prime is omitted, then it is for chemical standard states.

How can you tell if the standard Gibbs free energy given for a reaction is for chemical standard states or biological standard states?

The expression would relate to the intensive extraction of energy from intermediate compounds by redox reactions. Including the pyruvate dehydrogenase reaction, 5 of 9 reactions are redox reactions (in contrast with only 1 of 10 in glycolysis). According, energy is rapidly extracted from carbon compounds (yielding the energy-less CO2) and is transferred to NAD+ and FAD for subsequent utilization.

How could the expression "milking it for all it's worth' relate to the citric acid cycle?

Glucagon is a peptide, whereas epinephrine is an amino acid derivative.

How do glucagon and epinephrine differ in chemical structure?

Hexokinase can add a phosphate group to any of several 6 carbon sugars, whereas glucokinase is specific for glucose. Glucokinase has a lower affinity for glucose than does hexokinase. Consequently, glucokinase tends to deal with an excess of glucose, particularly in the liver. Hexokinase is the usual enzyme for phosphorylating 6-carbon sugars.

How do glucokinase and hexokinase differ in function?

Plant cell walls consist almost exclusively of carbohydrates, whereas bacterial cell walls contain peptides.

How do the cell wall of bacteria differ from those of plants?

The most important aspect of the amplification scheme is that the control mechanisms affect agents that are catalysts themselves. An enhancement by several powers of ten is itself increased by several powers of 10.

How do the control mechanisms in glycogen metabolism lead to amplification of response to a stimulus?

The enzyme beta-amylase is an exoglycosidase, degrading polysaccharides from the ends. The enzyme alpha-amylase is an endoglycosidase, cleaving internal glycosidic bonds.

How do the sites of cleavage of starch differ from one another when the cleavage reaction is catalyzed by alpha amylase and beta amylase?

ATP inhibits phosphofructokinase, consistent with the fact that ATP is produced by later reactions of glycolysis.

How does ATP act as an allosteric effector in the mode action of phosphofructokinase?

If the amount of ADP in a cell increases relative to the amount of ATP, the cell needs energy (ATP). This situation not only favors the reactions of the citric acid cycle, which release energy, activating isocitrate dehydrogenase, but also stimulates the formation of NADH and FADH2 for ATP production by electron transport and oxidative phosphorylation.

How does an increase in the ADP/ATP ratio affect the activity of isocitrate dehydrogenase?

If the amount of NADH in a cell increases relative to the amount of NAD+, the cell has completed number of energy releasing reactions. There is less need for the citric acid cycle to be active; as a result, the activity of pyruvate dehydrogenase is decreased.

How does an increase in the NADH/NAD+ ratio activity of pyruvate dehydrogenase?

Chitin is a polymer of N-acetyl-beta-D-glucosamine, whereas cellulose is a polymer of D-glucose. Both polymer play a structural role, but chitin occurs in the exoskeletons of invertebrates and cellulose primarily in plants.

How does chitin differ from cellulose in structure and function?

In the glucose-6-phosphate reaction, the concentration of substrate is the main determinant of reaction velocity. In the fructose-1,6-bisphosphatase reaction, allosteric effects are the main determinant of reaction velocity.

How does control of the glucose-6-phosphatase reaction?

Fructose-2,6-bisphosphate is an allosteric activator of phosphofructokinase (a glycolytic enzyme) and an allosteric inhibitor of fructose-1,6-bisphosphatase (an enzyme in the pathway of gluconeogenesis).

How does fructose-2,6-bisphosphate play a role as an allosteric effector?

Glycogen and starch differ mainly in the degree of chain branching. Both polymers serve as vehicles for energy storage, glycogen in animals and starch in plants.

How does glycogen differ from starch in structure and function?

In phosphorolysis, a bond is cleaved by adding the elements of phosphoric acid across the bond, whereas in hydrolysis, the cleavage takes place by adding the elements of water across the bond.

How does phosphorolysis differ from hydrolysis?

There is a transporter on the inner mitochondrial matrix that allows pyruvate from the cytosol to pass into the mitochondria.

How does pyruvate from glycolysis get to the pyruvate dehydrogenase complex?

In substrate level phosphorylation, the enrgy of hydrolysis of some compound provides sufficient energy to allow the endergonic phosphorylation of ADP to ATP to take place.

How does substrate level phosphorylation differ from phosphorylation linked to the electron transport chain?

AMP and fructose-2,6-bisphosphate are allosteric activators of phosphofructokinase. They are allosteric inhibitors of fructose-1,6-bisphosphatase.

How does the action of allosteric effectors differ in the reactions catalyzed by phosphofructokinase and fructose-1,6-bisphosphatase?

The ATP cost is the same, but more than 30 ATP can be derived from aerobic metabolism.

How does the cost of storing glucose-6-phosphate (G6P) as glycogen differ from the answer you obtained if G6P were used for energy in aerobic metabolism.

2 different orientations with respect to the sugar ring are possible for the hydroxyl group at the anomeric carbon. The 2 possibilities give rise to the new chiral center.

How does the cyclization of sugars introduce a new chiral center?

There is little effect in the reactions. Both are coenzymes involved in oxidation-reduction reactions. The presence of the phosphate distinguishes 2 separate pools of coenzymes so that different ratios of NADPH/NADP+ versus NADH/NAD+ can be maintained.

How does the difference between NADH and NADPH affect the reactions in which they are involved?

The hydrolysis of fructose-1,6-bisphosphate is a strongly exergonic reaction. The reverse reaction in glycolysis, phosphorylation of fructose-6-phosphate, is irreversible because of the energy supplied by ATP hydrolysis.

How does the hydrolysis of fructose-1,6-bisphosphate bring about the reversal of one of the physiologically irreversible steps of glycolysis?

Humans can digest glucose polymers containing alpha-bonds but not beta. For this reason, glycogen and starch are digestible, whereas cellulose is not. In addition, cellulose is fibrous rather than branched, which makes the polymer insoluble in water and inaccessible to digestion by humans.

How does the presence of alpha bonds versus beta bonds influence the digestibility of glucose polymers by humans? (hint there are 2 effects)

Without the release of chemical energy in exergonic reactions, the endergonic reactions in metabolism, especially those of biosynthesis of DNA and proteins, could not take place.

How does the release of chemical energy make metabolism possible?

In gluconeogenesis, glucose-6-phosphate is dephosphorylated to glucose (the last step of the pathway); in glycolysis, it isomerizes to fructose-6-phosphate (an early step in the pathway).

How does the role of glucose-6-phosphate in gluconeogenesis differ from that in glycolysis?

Glycogen is more extensively branched than starch. It is a more useful storage form of glucose for animals because the glucose can be mobilized more easily when there is a need for energy.

How is it advantageous for animals to convert ingested starch to glucose and then to incorporate the glucose into glycogen?

Anaerobically, 2 ATPs can be produced from one glucose molecule. Aerobically, this figure is 30 to 32, depending on which tissue it is occurring.

How many ATPs can be produced from one molecule of glucose anaerobically? Aerobically?

There are 4 chiral centers in the open chain form of glucose (carbons 2 through 5). Cyclization introduces another chiral center at the carbon involved in hemiacetal formation, giving a total of 5 chiral centers in the cyclic form.

How many chiral centers are there in the open-chain form of glucose? In the cyclic form?

5 enzymes are involved in the pyruvate dehydrogenase complex of mammals. Pyruvate dehydrogenase transfers a 2 carbon unit of TPP and releases CO2. Dihydrolipoyl transacetylase transfers the 2 carbon acetyl unit of lipoic acid and then to coenzyme A. Dihydrolipoyl dehydrogenase re-oxidizes lipoic acid and reduces NAD+ to NADH. Pyruvate dehydrogenase kinase phosphorylates PDH. PDH phosphatase removes the phosphate.

How many enzymes are involved in mammalian pyruvate dehydrogenase? What are their functions?

4 epimers of D-glucose exist, with inversion of configuration at a single carbon. the possible carbons at which this is possible are those numbered 2 through 5.

How many possible epimers of D-glucose exist?

The reshuffling reactions of the pentose phosphate pathway have both an epimerase and an isomerase. Without an isomerase, all the sugars involved are keto sugars, which are not substrates for transaldose, one of the key enzymes in the reshuffling process.

How would it affect the reactions of the pentose phosphate pathway to have an epimerase and not an isomerase to catalyze the reshuffling reactions?

A cellulase (an enzyme that degrades cellulose) needs an active site that can recognize glucose residues joined in a beta-glycosidic linkage and hydrolyze that linkage. An enzyme that degrades starch has the same requirements with regard to glucose residues joined in an alpha-glycosidic linkage.

How would you expect the active site of a cellulase to differ from the active site of an enzyme that degrades starch?

(A) NADH is oxidized, H+ + NADH --> NAD+ + 2 e- + 2H+. The aldehyde is reduced, CH3CH2CHO + 2e- + 2H+ ---> CH3CH2CH2OH. (B) Fe2+ is oxidized, Fe2+ --> Fe3+ + e-. Cu2+ is reduced, Cu2+ + e- --> Cu+

Identify the molecules oxidized and reduced in the following reactions and write the half reactions. (A) CH3CH2CHO + NADH ---> CH3CH2CH2OH + NAD+, (B) Cu2+ (aq) + Fe2+ (aq) --> Cu+ (aq) + Fe3+ (aq)

Greater than 3333 to 1

If a reaction can be written A --> B, and the delta G knot is 20 kJ mol^-1, what would the substrate/product ratio have to be for the reaction to be thermodynamically favorable?

The problem with lactic acid is that it is an acid. the H+ produced from lactic acid formation causes the burning muscle sensation. Sodium lactate intravenously is a good way to supply an indirect source of blood glucose.

If lactic acid is the buildup product of strenuous muscle activity, why is sodium lactate often given to hospital patients intravenously?

The size and complexity of the molecule make it more specific for particular enzyme-catalyzed reactions. In addition, it cannot cross membranes, so acyl-CoA molecules and other CoA derivatives can be segregated.

If the reactive part of coenzyme A is the thioester, why is the molecule so complicated?

Law of mass action

In chemistry, the relationship between concentrations of products and reactants in a system at equilibrium.

aldolase

In glycolysis, the enzyme that catalyzes the reverse aldol condensation of fructose-1,6-bisphosphate.

It "costs" 1 ATP equivalent (UTP to UDP) to add a glucose residue to glycogen. In degradation, about 90% of the glucose residues do not require ATP to produce glucose-1-phosphate. The other 10% require ATP to phosphorylate glucose. On average, this is another 0.1 ATP. Thus, the overall "cost" is 1.1 ATP, compared with the 3 ATP that can be derived from glucose-6-phosphate by glycolysis.

In metabolism, glucose-6-phosphate (G6P) can be used for glycogen synthesis or for glycolysis, among other fates. What does it cost, in terms of ATP equivalents, to store G6P as glycogen, rather than to use it for energy in glycolysis? The branched structure to glycogen leads to 90% of glucose residues being released as glucose-1-phosphate and 10% as glucose.

Thiamine pyrophosphate comes from the B1 vitamin thiamine. Lipoic acid is a vitamin. NAD+ comes from the B3 vitamin niacin. FAD comes from the B2 vitamin riboflavin.

In the PDH reaction alone, we can see cofactors that come from 4 different vitamins. What are they?

Starting with glucose-1-phsphate, the net yield is 3 ATP, because one of the priming reactions is no longer used. thus glycogen is more efficient fuel for glycolysis than free glucose.

In the muscles, glycogen is broken down via the following reaction: (glucose)n + Pi --> Glucose-1-phosphate + (Glucose)n-1 What would be the ATP yield per molecule of glucose in the muscle if glycogen were the source of the glucose?

The citric acid cycle takes place in the mitochondrial matrix. Glycolysis takes place in the cytosol.

In what part of the cell does the citric acid cycle take place? Does this differ from the part of the cell where glycolysis occurs?

The hexokinase molecule changes shape drastically on binding to substrate, consistent with the induced fit theory of an enzyme adapting itself to its substrate.

In what way is the observed mode of action of hexokinase consistent with the induced-fit theory of enzyme action?

Conversion of pyruvate to acetyl-CoA, conversion of iso-citrate to alpha-ketoglutarate, conversion of alpha-ketoglutarte to succinyl-CoA, conversion of succinate to fumarate, and conversion of malate to oxaloacetate.

In which steps of the aerobic processing of pyruvate are reduced electron carriers produced?

Conversion of pyruvate to acetyl-CoA, conversion of iso-citrate to alpha-ketoglutarate, conversion of alpha-ketoglutarte to succinyl-CoA,

In which steps of the aerobic processing of pyruvate is CO2 produced?

The conversion of fumarate to malate is a hydration reaction, not a redox reaction.

Is the conversion of fumarate to malate a redox (electron transfer) reaction? Why?

Phosphoenolpyruvate + ADP --> Pyruvate + ATP Delta G knot prime = -31.4 kJ/mol ADP + Pi -> ATP Delta G knot prime = 30.5 kJ/mol sum Delta G knot prime = -0.9 kJ/mol Thus, the reaction is thermodynamically possible under standard conditions.

Is the following reaction thermodynamically possible: Phosphoenolpyruvate + Pi + 2ADP --> Pyruvate + 2ATP Does this reaction happen in nature? Why?

The glycogen synthase reaction is exergonic overall because it is coupled to phosphate ester hydrolysis.

Is the glycogen synthase reaction exergonic or endergonic? What is the reason?

The reaction of 2-phosphoglycerate to phosphoenolpyruvate is a dehydration (loss of water) rather than a redox reaction.

Is the reaction of 2-phosphoglycerate to phosphoenolpyruvate a redox reaction? Why?

There is a connection and it is one of the most important points in chapter 15. It can e expressed in the equation delta G knot = -RTInKeq

Is there a connection between the free-energy change for a reaction and its equilibrium constant? If there is a connection, what is it?

In red blood cells, the presence of the reduced form of glutathione is necessary for the maintenance of the sulfhydryl groups of hemoglobin and other proteins in their reduced forms, as well as for keeping the Fe(II) of hemoglobin in its reduced form. Glutathione also maintains the integrity of red cells by reacting with peroxides that would otherwise degrade fatty acid side chains in the cell membrane.

List 2 ways in which glutathione functions in red blood cells.

NADPH has one more phosphate group than NADH (at the 2' position of the ribose ring of the adenine nucleotide portion of the molecule). NADH is produced in oxidative reactions that give rise to ATP. NADPH is a reducing agent in biosynthesis. The enzymes that use NADH as a coenzyme are different from those that require NADPH.

List 3 differences in structure or function between NADH and NADPH.

Oxidative decarboxylation

Loss of carbon dioxide accompanied by oxidation.

The part of the active site that binds to NADH would be the part that is most conserved, since many dehydrogenases use that coenzyme.

Many NADH-linked dehydrogenases have similar active sites. Which part of glyceraldehyde-3-phosphate dehydrogenase would be the most conserved between other enzymes?

Yes, not only is citric acid completely degraded to carbon dioxide and water, but it is also readily absorbed into the mitochondrion.

Many soft drinks contain citric acid as a significant part of their flavor. Is this a good nutrient?

There would be 15 possible isozymes of LDH, combining 3 different subunits into combinations of 4. Besides the 5 isozymes containing only M and H, there would also be C4, CH3, C2H2, CH2M, C2HM, C3M, and CM3.

Many species have a 3rd type of LDH subunit that is found predominantly in the testes. If this subunit, called C, were expressed in other tissues and could combine with the M and H subunits, how many LDH isozymes would be possible? What would their compositions be?

Glyoxysomes

Membrane enclosed organelles that contain the enzymes of the glyoxylate cycle.

enantiomers

Mirror-image, non-superimposable stereoisomers.

stereoisomers (optical isomers)

Molecules that differ from each other only in their configuration (3D shape).

Animals that have been run to death have accumulated large amounts of lactic acid in their muscle tissue, accounting for the sour taste of the meat.

Most hunters know that meat from animals that have been run to death tastes sour. Why is this so?

With few exceptions, a biochemical reaction typically results in only one chemical modification of the substrate. Accordingly, several to many steps are needed to reach the ultimate goal.

Most metabolic pathways are relatively long and appear to be very complex. For example, there are 10 individual chemical reactions in glycolysis, converting glucose to pyruvate. Why is it complex?

Isozymes

Multiple forms of an enzyme that catalyze the same overall reaction but have subtle physical and kinetic parameters

The following series of reactions exchanges NADH for NADPH. Oxaloacetate + NADH + H+ --> Malate + NAD+ Malate + NADP+ --> Pyruvate + CO2 + NADPH + H+

NADH is an important coenzyme in catabolic processes, whereas, NADPH appears in anabolic processes. How can an exchange of the two can be effected?

Differences; sucrose contains fructose, whereas lactose contains galactose. Sucrose has an a beta (1 -> 2) glycosidic linkage. Similarities: sucrose and lactose are both disaccharides, and both contain glucose.

Name 2 differences between sucrose and lactose. Name 2 similarities.

Allosteric effects and covalent modification are 2 important forms of control of enzymatic action. Covalent modification plays a more important role than allosteric effects in glycogen breakdown.

Name 2 forms of control of enzymatic action. Which of the 2 is more important in control of glycogen synthesis?

Glycogen synthase is subject to covalent modification and to allosteric control. The enzyme is active in its phosphorylated form and inactive when dephosphorylated. AMP is an allosteric inhibitor of glycogen synthase, whereas ATP and glucose-6-phosphate are allosteric activators.

Name two control mechanisms that play a role in glycogen biosynthesis. Give an example of each.

D-Mannose and D-galactose are both epimers of D-glucose, with inversion of configuration around carbon atoms 2 and 4, respectively; D-ribose has only 5 carbons, but the rest of the sugars named in this question have 6.

Name which, if any, of the following are epimers of D-glucose: D-mannose, D-galactose, D-ribose

All groups are aldose-ketose pairs.

Name which, if any, of the following groups are not aldose-ketose pairs: D-ribose and D-ribulose, D-glucose and D-fructose, D-glyceraldehyde and dihydroxyacetone.

The digestive tract of these animals contains bacteria that have the enzyme to hydrolyze cellulose.

No animal can digest cellulose. Reconcile this statement with the fact that many animals are herbivores that depend heavily on cellulose as a food source.

diastereomers

Non-superimposable, non-mirror image stereoisomers.

Alpha-ketoglutarate dehydrogenase complex

One of the enzymes of the citric acid cycle; it catalyzes the conversion of alpha-ketoglutarate to succinyl-CoA

anomers

One of the possible stereoisomers formed when a sugar assumes the cyclic form.

Group 1: catabolism, oxidative, energy-yielding. Group 2: anabolism, reductive, energy-requiring

Organize the following words into 2 related groups: catabolism, energy-requiring, reductive, anabolism, oxidative, energy-yielding.

Each glucose residue is added to the growing glycogen molecule by transfer from UDPG.

Outline the role of UDPG in glycogen biosynthesis.

starches

Polymers of glucose that play an energy-storage role in plants.

Oxidation-reduction reactions

Reactions that involve transfer of electrons from one reactant to another.

(A) Using a high energy phosphate to phosphorylate a substrate. (B) Changing the form of a molecule without changing its empirical formula (i.e., replacing one isomer for another) (C) Performing an aldol cleavage of a sugar to yield 2 smaller sugars or sugar derivatives. (D) Changing the oxidation state of a substrate by removing hydrogen while simultaneously changing the oxidation state of the coenzyme (NADH, FADH2, etc.)

Several of the enzymes of glycolysis fall into classes that we will see often in metabolism. What reaction types are catalyzed by each of the following: (A) Kinases (B) Isomerases (C) Aldolases (D) Dehydrogenases

A positive delta G knot prime does not necessarily mean that the reaction has a positive delta G. Substrate concentrations can make a negative delta G out of a positive delta G knot prime.

Several reactions have very positive delta G knot values. How can this be explained, given that these reactions do occur in the cell?

Sprints and similar short periods of exercise rely on anaerobic metabolism as a source of energy, producing lactic acid. Longer periods of exercise draw on aerobic metabolism and will produce lactic acid.

Short periods of exercise, such as sprints, are characterized by lactic acid production and the condition known as oxygen debt. Give a reason why this is so.

The enrgy released by all he reactions of glycolysis is 184.5 kJ mol^-1 glucose^-1. The energy released by glycolysis drives the phosphorylation of 2 ADP to ATP for each molecule of glucose, trapping 61.0 kJ mol^-1 glucose^-1. The estimate of 33% efficiency comes from the calculation (61.0/184.5) x 100 = 33%

Show how the estimate of 33% efficiency of energy use in anaerobic glycolysis is derived.

(A) By using only the oxidative reactions. (B) By using the oxidative reactions, the transaldolase and transketolase reactions in reverse. (C) By using glycolytic reactions and the transaldolase and transketolase reactions in reverse.

Show how the pentose phosphate pathway, which is connected to the glycolytic pathway, can do the following. (A) Make both NADPH and pentose phosphates, in roughly equal amounts. (B) Make mostly or only NADPH (C) Make mostly or only pentose phosphates.

In both pathways, the overall reaction is ATP + 2H2O --> AMP + 2 Pi. thermodynamic parameters, such as energy, are additive. The overall energy is the same because the overall pathway is the same.

Show that the hydrolysis of ATP to AMP and 2Pi releases the same amount of energy by either of the 2 following pathways. Pathway 1 ATP + H2O--> ADP + Pi ADP + H2O--> AMP + Pi Pathway 2 ATP + H2O--> AMP + Pi (pyrophosphate) PPi + H2O--> AMP + Pi

Add the delta G knot prime mol^-1 values for the reactions from glucose to glyceraldehyde-3-phosphate. The result is 2.5 kJ mol^-1 = 0.6 kcal mol^-1

Show that the reaction Glucose --> 2 Glyceraldehyde-3-phosphate is slightly endergonic (delta G knot = 2.2 kJ mol^-1 = 0.53 kcal mol^-1); that is, it is not too far from equilibrium.

Carbon-1 of glyceraldehyde is the aldehyde group. It changes oxidation state to a carboxylic acid, which is phosphorylated simultaneously.

Show the carbon atom that changes oxidation state during the reaction catalyzed by glyceraldehyde-3-phosphate dehydrogenase. What is the functional group that changes during the reaction?

Phosphoenolpyruvate --> pyruvate + Pi delta G knot prime = -61.9 kJ mol^-1 = -14.8 kcal mol^-1 ADP + Pi --> ATP delta G knot prime = 30.5 kJ mol^-1 = 7.3 kcal mol^-1 Phosphoenolpyruvate + ADP --> Pyruvate + ATP delta G knot prime = -31.4 kJ mol^-1 = -7.5 kcal mol

Show, by a series of equations, the energetics of phosphorylation of ADP by phosphoenolpyruvate.

Athletes try t increase their stores of glycogen before an event. The most direct way to increase the amount of this polymer of glucose is to eat carbohydrates.

Some athletes eat high diets in carbohydrates before an event. Suggest a biochemical basis for this practice.

The sum of the energies of the individual reactions is -44.3 kJ (-10.6 kcal) for each mole of acetyl-CoA that enters the cycle.

Some reactions of the citric acid cycle are endergonic. How is this so?

epimers

Stereoisomers that differ only in configuration around one of several chiral carbon atoms.

oligosaccharides

Sugars linked by glycosidic bonds

Reducing sugars

Sugars that have a free carbonyl group, one that can react with an oxidizing agent.

amino sugars

Sugars with a substituted amino group as part of its structure

Muscle tissue uses large quantities of glucose, producing lactate in the process. the liver is an important site of gluconeogenesis to recycle the lactate to glucose.

Suggest a reason or reasons why the Cori cycle takes place in the liver and in muscle.

Having different reducing agents for anabolic and catabolic pathways keeps the pathways separate metabolically. thus, they are subject to independent control and do not waste energy.

Suggest a reason why a different reducing agent (NADPH) is used in anabolic reactions rather than NADH, which plays a role in catabolic ones.

Sugar nucleotides are diphosphates. The net result is hydrolysis to 2 phosphate ions, releasing more energy and driving the addition of glucose residues to glycogen in the direction of polymerization.

Suggest a reason why sugar nucleotides, such as UDPG, play a role in glycogen synthesis, rather than sugar phosphates, such as glucose-6-phosphate.

This polymer would be expected to have a structural role. The presence of the beta-glycosidic linkage makes it useful as food only to termites or to ruminants, such as cows and horses; these animals harbor bacteria capable of attacking the beta-linkage in their digestive tracts.

Suppose that a polymer of glucose with alternating alpha (1-->4) and beta (1-->4) glycosidic linkages has just been discovered. Would you expect this polymer to have primarily a structural role or an energy storage role in organisms? What sort of organisms, if any, could use this polysaccharide as a food source?

configuration

The 3D arrangement of groups around a chiral carbon atom.

Glutamic acid has an acid side chain with a pKa of 4.25. Therefore, it would be negatively charged at pH 8.6 and the H subunit would move more toward the anode (+) than the M subunit. Thus LDH 1, would move the farthest. LDH 5, which is M4, would move the least, with other isozymes migrating between those 2 extremes proportional to their H content.

The M and H subunits of lactate dehydrogenase have very similar sizes and shapes but differ in amino acid composition. If the only difference between the 2 were that the H subunit had a glutamic acid in a position where the M subunit had a serine, how would the 5 isozymes of LDH separate on electrophoresis using a gel at pH 8.6?

phosphorolysis

The addition of phosphoric acid across a bond, such as the glycosidic bond in glycogen, giving glucose phosphate and a glycogen remainder one residue shorter; it is analogous to hydrolysis (addition of water across a bond)

Glycolysis

The anaerobic breakdown of glucose to three-carbon compounds.

Catabolism

The breakdown of nutrients to provide energy.

anomeric carbon

The chiral center created when a sugar cyclizes.

The sprint is essentially anaerobic and lactate from glucose by glycolysis. Lactate is then recycled to glucose by gluconeogenesis.

The concentration of lactate in blood rises sharply during a sprint and declines slowly for about an hour afterward. What causes the rapid rise in lactate concentration? What causes the decline in lactate concentration after the run?

Substrate cycling

The control process in which opposing reactions are catalyzed by different enzymes.

The overall delta G knot prime = -260.4 kJ mol^-1 or -62.3 kcal mol^-1. The reaction is exergonic, because it has a large, negative delta G knot prime.

The delta G knot for the reaction Citrate ----> Isocitrate is +6.64 kJ mol^-1 = +1.59 kcal mol^-1. The delta G knot for the reaction Isocitrate ---> alpha Ketoglutarate is -267 kJ mol^-1 = -63.9 kcal mol^-1. What is the delta G knot for the conversion of citrate to alpha ketoglutarate? Is it exergonic or endergonic, why?

Phosphorylase beta

The dephosphorylated form of glycogen phosphorylase.

Lactose

The disaccharide formed when galactose and glucose are bonded together.

Sucrose

The disaccharide formed when glucose and fructose are bonded together.

Isocitrate lyase

The enzyme that catalyzes the cleavage of isocitrate to glyoxylate and succinate.

Enolase

The enzyme that catalyzes the conversion of 2-phosphoglycerate to phosphoenolpyruvate

Alcohol dehydrogenase

The enzyme that catalyzes the conversion of acetaldehyde to ethanol.

triosephosphate isomerase

The enzyme that catalyzes the conversion of dihydroxyacetone phosphate to glyceraldehyde-3-phosphate.

Fumarae

The enzyme that catalyzes the conversion of fumarate to malate.

glucose phosphate isomerase

The enzyme that catalyzes the conversion of glucose-6-phosphate to fructose-6-phosphate

Malate dehydrogenase

The enzyme that catalyzes the conversion of malate to oxaloacetate.

Succinate dehydrogenase

The enzyme that catalyzes the conversion of succinate to fumarate.

Succinyl-CoA synthetase

The enzyme that catalyzes the conversion of succinyl-CoA and GDP to succinate and GTP, releasing CoA-SH.

Pyruvate kinase

The enzyme that catalyzes the final step common to all forms of glycolysis.

Isocitrate dehydrogenase

The enzyme that catalyzes the first of the two oxidative decarboxylations of the citric acid cycle.

Citrate synthase

The enzyme that catalyzes the first step of the citric acid cycle.

Glycogen synthase

The enzyme that catalyzes the growth of glycogen chains.

Phosphoglyceromutase

The enzyme that catalyzes the isomerization of 3-phosphoglycerate to 2-phosphoglycerate.

Phosphoglucomutase

The enzyme that catalyzes the isomerization of glucose-1-phosphate to glucose-6-phosphate.

Glycogen phosphorylase

The enzyme that catalyzes the phosphorolysis of glycogen to give glucose-1-phosphate.

Malate synthase

The enzyme that catalyzes the reaction of glyoxylate with acetyl-CoA to produce malate.

Branching enzyme

The enzyme that catalyzes the reactions needed to introduce a branch point during the synthesis of glycogen.

Phosphoglycerate kinase

The enzyme that catalyzes the transfer of a phosphate group from 1,3-biphophoglycerate to ATP.

The 2nd half reaction (the 1 involving NADH) is that of oxidation; the 1st half reaction (the one involving O2) is that of reduction. The overall reaction is 1/2 O2 + NADH + H+ ---> H2O + NAD+. O2 is the oxidizing agent and NADH is the reducing reagent.

The following half reactions play important roles in metabolism. 1/2 O2 + 2H+ + 2 e- --> H2O and NADH + H+ ----> NAD+ + 2H+ + 2 e-. Which of these 2 is a half reaction of oxidation? Which one is reduction? Write the equation for the overall reaction. Which reagent is the oxidizing agent (electron acceptor)? Which reagent is the reducing (electron donor)?

reduction

The gain of electrons.

The citric acid cycle occurs in the mitochondrial matrix, which is more selective in its permeability than the plasma membrane.

The intermediates of glycolysis are phosphorylated, but those of the citric acid cycle are not. Why?

phosphofructokinase

The key allosteric control enzyme in glycolysis; it catalyzes the phosphorylation of fructose-6-phosphate.

oxidation

The loss of electrons

The enzyme contains a phosphate group on a suitable amino acid, such as serine, threonine, or histidine. the substrate donates its phosphate group from the C-3 position to another amino acid on the enzyme, subsequently receiving one that started out on the enzyme. Thus, the 32P that was on the substrate is transferred to the enzyme, while an unlabeled phosphorus is put on the C-2 position.

The mechanism involved in the reaction catalyzed by phosphoglyceromutase is known to involve a phosphorylated enzyme intermediate. If 3-phosphoglycerate is radioactively labeled with 32P, the product of the reaction, 2-phosphoglycerate, does not have any radioactive label. Design a mechanism to explain these facts.

Mitochondrial matrix

The part of the mitochondrion enclosed by the inner mitochondrial membrane.

Anaerobic glycolysis

The pathway of conversion of glucose to lactate; distinguished from glycolysis, which is the conversion of glucose to pyruvate.

Gluconeogenesis

The pathway of synthesis of glucose from lactate.

Phosphorylase alpha

The phosphorylated form of glycogen phosphorylase.

antigenic determinants

The portions of a molecules that antibodies recognize as foreign and to which they bind.

Coupling

The process by which an exergonic reaction provides energy for an endergonic one.

activation in bioenergetics

The process of bonding a metabolite to another molecule so that the next reaction of the metabolite is energetically favorable.

Intermembrane space

The region between the inner and outer mitochondrial membranes.

Standard states

The standard set of conditions used for comparisons of chemical reactions.

L-Sorbitol was named early in biochemical history as a derivative of L-sorbose. Reduction of D-glucose gives a hydroxy sugar that could easily be named D-glucitol, but it was originally named L-sorbitol and the name stuck.

The sugar alcohol often used in "sugarless" gums and candies is L-sorbitol. Much of this alcohol is prepared by reduction of D-glucose. Compare these 2 structures and explain how this can be.

Metabolism

The sum total of all biochemical reactions that take place in an organism.

Anabolism

The synthesis of biomolecules from simpler compounds.

Glucose-6-phosphate is oxidized, and NADP+ is reduced. NADP+ is the oxidizing agent and glucose-6-phosphate is the reducing agent

There is a reaction in carbohydrate metabolism in which glucose-6-phosphate reacts with NADP+ to give 6-phosphoglucono-gamma-lactone and NADPH. In this reaction, which substance is oxidized, and which one is reduced? Which one is the oxidizing agent, and which one is the reducing?

FAD is reduced, and succinate is oxidized. FAD is the oxidizing agent and succinate is the reducing agent.

There is a reaction in which succinate reacts with FAD to give fumarate and FADH2. In this reaction, which substance is oxidized, and which one is reduced? Which one is the oxidizing agent, and which one is the reducing?

Lactose is a disaccharide of glucose and galactose. There is no energy cost in the hydrolysis of the bond between the 2 monosaccharides, so essentially there are 2 hexoses yields the same amount of energy, the aerobic processing of lactose would lead to 60 to 64 ATPs, depending on the tissue and on the shuttle system used.

Using the information found in chapters 17-19, calculate the amount of ATP that can be produced from 1 molecule of lactose metabolized aerobically through glycolysis and the citric acid cycle.

NADH and FADH2 are indirect sources of energy produced in the TCA cycle, GTP is a direct source of energy.

What 3 molecules produced during the citric acid cycle are an indirect or direct source of high energy compounds?

Glucose-6-phosphate can be converted to glucose (gluconeogenesis), glycogen, pentose phosphates (pentose phosphate pathway), or pyruvate (glycolysis).

What are 4 possible metabolic fates of glucose-6-phosphate?

Glycoproteins are ones in which carbohydrates are covalently bonded to proteins. They play a role in eukaryotic cell membranes, frequently as recognition sites for external molecules. Antibodies (immunoglobulins) are glycoproteins.

What are glycoproteins? What are some of their biochemical roles?

The cell walls of plants consist mainly of cellulose, whereas those of bacteria consist mainly of polysaccharides with peptide crosslinks.

What are some of the main differences between the cell walls of plants and those of bacteria?

ATP and NADH are the 2 most common inhibitors

What are the 2 most common inhibitors of steps of the citric acid cycle and the reaction catalyzed by pyruvate dehydrogenase?

A variety of reactions in which amino acids are converted to citric acid cycle intermediates are considered anaplerotic. In addition, pyruvate + CO2 can form oxaloacetate via pyruvate carboxylase.

What are the anaplerotic reactions in mammals?

The citric acid cycle is also called the Krebs cycle, the tricarboxylic acid cycle, and the TCA cycle.

What are the different names used to describe the pathway discussed in chapter 19?

The enzymes that reduce NAD+ are all soluble, matrix enzymes, while succinate dehydrogenase is membrane-bound. The NAD+-linked dehydrogenases all catalyze oxidations that involve carbons and oxygens, such as an alcohol group being oxidized to an aldehyde or aldehyde to carboxylic acid. The FAD-linked dehydrogenase oxidizes a carbon-carbon single bond to a double bond

What are the major differences between the oxidations in the citric acid cycle that use NAD+ as an electron acceptor and ones that uses FAD?

Individuals who lack the gene that directs the synthesis of the M form of the enzyme can carry on glycolysis in their livers but experience muscle weakness because they lack the enzyme in muscle.

What are the metabolic effects of not being able to produce the M subunit of phosphofructokinase?

(A) The aldehyde is the oxidizing agent; NADH is the reducing agent. (B) Cu2+ is the oxidizing agent; Fe2+ is the reducing agent.

What are the oxidizing agent and reducing agents in the following reactions? (A) CH3CH2CHO + NADH ---> CH3CH2CH2OH + NAD+, (B) Cu2+ (aq) + Fe2+ (aq) --> Cu+ (aq) + Fe3+ (aq)

Pyruvate can be converted to lactate, ethanol, or acetyl-CoA.

What are the possible metabolic fates of pyruvate?

The reactions proceed by the same mechanism and use the same cofactors. the difference is the initial substrate, which is pyruvate or alpha-ketoglutarate. During the course of the reaction, pyruvate dehydrogenase shuttles an acetyl unit through the reaction while alpha-ketoglutarate dehydrogenase shuttles a succinyl unit.

What are the similarities and differences between the reactions catalyzed by pyruvate dehydrogenase and alpha ketoglutarte dehydrogenase?

Vitamin C is a lactone (a cyclic ester) with a double bond between 2 of the ring carbons. The presence of the double bond makes it susceptible to air oxidation.

What are the structural differences between vitamin C and sugars? These structural differences play a role in the susceptibility of this vitamin to air oxidation?

ATP is less stable than ADP and Pi because of the charge distribution and loss of the resonance stabilization in the phosphate ion. There is stabilization (dispersal of energy) when ATP is hydrolyzed, leading to a negative free-energy change. ADP + Pi + H+ --> ATP + H2O Delta G knot prime = 30.5 kJ mol^-1 or 7.3 kcal mol^-1

What are the usual ionic forms of ATP and ADP in typical cells? Does this information have any bearing on the free-energy change for the conversion of ATP to ADP.

The conversion of isocitrate to succinate and glyoxylate catalyzed by isocitrate lyase and the conversion of glyoxylate and acetyl-CoA to malate catalyzed by malate synthase.

What are unique reactions of the glyoxylate cycle?

The free energy change can be used to predict the spontaneity of a reaction under conditions of constant temperature and pressure.

What conditions are necessary for the free energy change to be used to predict the spontaneity of a reaction?

Reaction would take place only if it is coupled to an exergonic reaction.

What do the following indicators tell you about whether a reaction can proceed as written? (A) The standard free-energy change is positive.

Reaction would proceed only if coupled to an exergonic reaction.

What do the following indicators tell you about whether a reaction can proceed as written? (B) The free energy change is positive.

Reaction would proceed as written.

What do the following indicators tell you about whether a reaction can proceed as written? (C) The reaction is exergonic.

It means that the reaction catalyzed by the enzyme produces the product that is part of the name and does not require a direct input of energy from a high energy phosphate. Thus, citrate synthase catalyzes the synthesis of citrate without using ATP to do it.

What does it mean when an enzyme has the name synthase?

A synthetase is an enzyme that synthesizes a molecule and uses a high energy phosphate in the process.

What does it mean when an enzyme is called a synthetase?

The bubbles in beer are CO2, produced by alcoholic fermentation. Tired and aching muscles are caused in part by a buildup of lactic acid, a product of anaerobic glycolysis.

What does the material of chapter 17 have to do with beer? What does it have to do with tired and aching muscles?

NAD+ and FAD are the primary electron acceptors of the citric acid cycle.

What electron acceptors play a role in the citric acid cycle?

Transketolase catalyzes the transfer of a 2 carbon unit, whereas transaldolase catalyzes the transfer of a 3 carbon unit.

What is a major difference between transketolase and transaldolase?

A reducing sugar is one that has a free aldehyde group. The aldehyde is easily oxidized, thus reducing the oxidizing agent.

What is a reducing sugar?

Fluoroacetate is a poison that is produced naturally in some plants and is also used as a poison against undesirable pests. It is poisonous because it is used by citrate synthase to make fluorocitrate, which is an inhibitor of the citric acid cycle.

What is fluoroacetate? Why is it used?

Amphibolic means that the pathway is involved in both catabolism and anabolism.

What is meant by the stament that a pathway is amphibolic?

The Cori cycle is a pathway in which there is no net change except for the hydrolysis of ATP. However , substrate cycles allow for increased control over opposing reactions when they are catalyzed by different enzymes.

What is the Cori cycle?

The Warburg effect is the high level of glycolysis in cancer cells, giving rise to pyruvate, followed by lactic acid fermentation. This effect is observed even at high levels of oxygen, where further oxidation to carbon dioxide and water is expected. This is one of many aspects of glycolysis.

What is the Warburg effect, and what does it have to do with the topics in chapter 17?

5 enzymes are all in close proximity for efficient shuttling of the acetyl unit between molecules and efficient control of the complex by phosphorylation.

What is the advantage to the organization of the PDH complex?

Fiber binds many toxic substances in the gut and decreases the transit time of ingested food in the digestive tract, so that harmful compounds such as carcinogens are removed from the body more quickly than would be the case with a low fiber diet.

What is the benefit of fiber in the diet?

In a sugar phosphate, an ester bond is formed between one of the sugar hydroxyls and phosphoric acid. A glycosidic bond is an acetal, which can be hydrolyzed to regenerate the 2 original sugar hydroxyls.

What is the chemical difference between a sugar phosphate and a sugar involved in a glycosidic bond?

Hemolytic anemia is caused by defective working of the pentose phosphate pathway. there is a deficiency of NADPH, which indirectly contributes to the integrity of the red blood cells. The pentose phosphate pathway is the only source of NADPH in red blood cells.

What is the connection between material in chapter 18 and hemolytic anemia?

20 kJ mol^-1, 0 kJ mol^-1, 30 kJ mol^-1

What is the delta G knot for the following values of Keq: 1 x 10^4, 1, and 1 x 10^-6

Enantiomers are non-superimposable, mirror-image stereoisomers. Diastereomers are non-superimposable, non-mirror image stereoisomers.

What is the difference between an enantiomer and a diastereomer?

An isomerase is a general term for an enzyme that changes the form of a substrate without changing its empirical formula. A mutase is an enzyme of the isomerase class that moves a functional group, such as a phosphate, to a new location in the substrate molecule.

What is the difference between an isomerase and a mutase?

(A) Increasing the level of ATP favors both gluconeogenesis and glycogen synthesis. (B) Decreasing the level of fructose-1,6-bisphosphate would tend to stimulate glycolysis, rather than gluconeogenesis or glycogen synthesis. (C) Levels of fructose-6-phosphate do not have a marked regulatory effect on these pathways of carbohydrate metabolism

What is the effect on gluconeogenesis and glycogen synthesis of (A) increasing the level of ATP, (B) decreasing the concentration of fructose-1,6-bisphosphate, and (C) increasing the concentration of fructose-6-phosphate?

Both cellulose and starch are polymers of glucose. In cellulose, the monomers are joined by a beta-glycosidic linkage, whereas in starch they are joined by an alpha-glycosidic linkage.

What is the main structural difference between cellulose and starch?

Glycogen exists as a highly branched polymer. Starch can have both a linear and branched form, which is not as highly branched as that of glycogen.

What is the main structural difference between glycogen and starch?

Conversion of glucose to lactate rather than pyruvate recycles NADH.

What is the metabolic advantage in the conversion of glucose to lactate, in which there is no net oxidation or reduction?

The 2 enzymes can have different tissue locations and kinetic parameters. The glucokinase has a higher Km for glucose than hexokinase. Thus, under conditions of low glucose, the liver does not convert glucose to glucose-6-phosphate, using the substrate that is needed elsewhere. When the glucose concentration is much higher, however, glucokinase helps phosphorylate glucose so that it can be stored as glycogen.

What is the metabolic advantage of having both hexokinase and glucokinase to phosphorylate glucose?

In some cases, the enzyme that degrades lactose (milk sugar) to its components - glucose and galactose - is missing. In other cases, the enzyme isomerizes galactose to glucose for further metabolic breakdown.

What is the metabolic basis for the observation that many adults cannot ingest large quantities of milk without developing gastric difficulties?

The purpose of the step that produces lactic acid is to reduce pyruvate so that NADH can be oxidized to NAD+, which is needed for the step catalyzed by glyceraldehyde-3-phosphate dehydrogenase.

What is the metabolic purpose of lactic acid production?

Small energy changes generally involve mild conditions. Also, such reactions are more sensitive to relatively small changes in concentration and thus are easier to control.

What is the molecular logic that makes a pathway with a number of comparatively small energy changes more likely than a single reaction with a large energy change?

There is a net gain of 2 ATP molecules per glucose molecule consumed in glycolysis. The gross yield is 4 ATP molecules per glucose molecule, but the reaction of glycolysis require 2 ATP per glucose.

What is the net gain of ATP molecules derived from the reactions of glycolysis? How do these results differ from the gross yield of ATP?

Biotin is the molecule to which carbon dioxide is attached to the process of being transferred to pyruvate. The reaction produces oxaloacetate, which then undergoes further reactions of gluconeogenesis.

What is the role of biotin in gluconeogenesis?

Each glucose residue added to a growing phosphate chain comes from uridine diphosphate glucose. the cleavage of the phosphate ester bond to the nucleoside diphosphate moiety supplies the needed energy.

What is the source of the energy needed to incorporate glucose residues into glycogen? How is it used?

In NADPH, the hydroxyl of the ribose attached to the adenine has a phosphate attached.

What is the structural difference between NADH and NADPH?

The important part of TPP is the 5 membered ring, in which a carbon is found between nitrogen and sulfur. This carbon forms a carbanion that is extremely reactive, making it able to perform a nucleophilic attack on carbonyl groups, leading to decarboxylation of several compounds in different pathways.

What is unique about TPP that makes it useful in decarboxylation reactions?

This compound contains a lactic acid side chain.

What is unusual about the structure of N-acetylmuramic acid compared with the structures of other carbohydrates?

Reactions that require acetyl-CoA: none. Reactions that require biotin: carboxylation of pyruvate to oxaloacetate.

What reactions in chapter 18 require acetyl-CoA or biotin?

Insulin triggers the series of events that leads to glycogen synthesis.

What role does insulin play in glycogen synthesis?

Glucagon and epinephrine start the chain of events leading to glycogen breakdown.

What roles do glucagon and epinephrine play in glycogen breakdown?

The net yield of ATP from glycolysis is the same, 2 ATP, when either of the 3 substrates is used. The energetics of the conversion of hexoses to pyruvate are the same, regardless of hexose type.

What should be the net ATP yield for glycolysis when fructose, mannose, and galactose are used as the starting compounds? Why?

NAD+, NADP+, and FAD all contain an ADP moiety.

What structural feature do NAD+, NADP+, and FAD have in common?

These enzymes catalyze oxidative decarboxylations.

What type of reaction is catalyzed by isocitrate dehydrogenase and alpha ketoglutarate dehydrogenase?

NAD+ is the oxidizing agent n reactions in which a nutrient is the substance to be oxidized. Like all oxidizing agents, NAD+ is reduced, producing NADH

Which coenzyme is a reactant in the oxidation of a nutrient, NAD+ or NADH? Why?

Isocitrate dehydrogenase, alpha ketoglutarate dehydrogenase, and succinyl-CoA synthetase.

Which enzymes of the citric acid cycle are missing from the glyoxylate cycle?

Hexokinase is inhibited by glucose-6-phosphate. Phosphofructokinase is inhibited by ATP and citrate. Pyruvate kinase is inhibited by ATP, acetyl-CoA, and alanine. Phosphofructokinase is stimulated by AMP and fructose-2,6-bisphosphate.

Which molecules act as inhibitors of glycolysis? Which molecules act as activators?

NADH-linked dehydrogenases;: Glyceraldehyde-3-phophohate dehydrogenase, lactate dehydrogenase, and alcohol dehydrogenase.

Which of the enzymes discussed in the chapter 17 are NADH-linked dehydrogenases?

Statement (A) is true, but statement (B) is not. The standard state of solutes is normally defined as unit activity (1 M for all but the most careful work). In biological systems, the pH is frequently in the neutral range (i.e., H+ is close to 10^-7 M); the modification is a matter of convenience. Water is the solvent, not the solute, and its standard state is the pure liquid.

Which of the following statements is true about the modified standard state for biochemistry? Why or why not. (A) [H+] = 1 x 10^-7 M, not 1 M. (B) The concentration of any solute is 1 x 10^7 M.

None of these statements is true. Some coenzymes are involved in group-transfer reactions. Many coenzymes contain phosphate groups, and CoA contains sulfur. ATP does not represent stored energy, but is generated on demand.

Which of the following statements is true? (A) All coenzymes are electron-transfer agents. (B) Coenzymes do not contain phosphorus or sulfur. (C) Generating ATP is a way of storing energy.

Anaerobic glycolysis is the principal pathway for the anaerobic metabolism of glucose. The pentose phosphate pathway can also be considered. Aerobic glycolysis and the citric acid cycle are responsible for the aerobic metabolism of glucose.

Which pathways are involved in the anaerobic metabolism of glucose? Which pathways are involved in the aerobic metabolism of glucose?

Reactions that require NADH: reduction of pyruvate to lactate and reduction of acetaldehyde to ethanol. Reactions that require NAD+: oxidation of glyceraldehyde-3-phosphate to give 1,3-diphosphoglycerate. Enzymes that catalyze reactions requiring NADH: lactate dehydrogenase and alcohol dehydrogenase. Enzymes that catalyze reactions requiring NAD+: glyceraldehyde-3-phosphate dehydrogenase.

Which reaction in chapter 17 require NADH? Which reaction require NAD? List the enzymes that catalyze the reaction that require NADH and that require NAD+.

Reactions that require ATP: formation of UDP-glucose from glucose-1-phosphate and UTP (indirect requirement, because ATP is needed to regenerate UTP), regeneration of UTP, and carboxylation of pyruvate to oxaloacetate. Reactions that produce ATP: none. Enzymes that catalyze ATP-requiring reactions: UDP-glucose phosphorylase (indirect requirement), nucleotide phosphate kinase, and pyruvate carboxylase. Enzymes that catalyze ATP-producing reactions: none.

Which reaction or reactions discussed in chapter 18 require ATP? Which reaction or reactions produce ATP? List the enzymes that catalyze the reactions that require and that produce ATP.

Reactions that require ATP: phosphorylation of glucose to give glucose-6-phosphate and phosphorylation of fructose-6-phosphate to give fructose-1,6-bisphosphate. Reactions that produce ATP: transfer of phosphate group from 1,3-bisphosphoglycerate to ADP and transfer of phosphate group from phosphoenolpyruvate to ADP. Enzymes that catalyze reactions requiring ATP: hexokinase, glucokinase, and phosphofructokinase. Enzymes that catalyze reactions producing ATP: phosphoglycerate kinase and pyruvate kinase.

Which reaction or reactions that we have met in this chapter (17) require ATP? Which reactions produce ATP? List the enzymes that catalyze the reactions that require and that produce ATP.

The control points in glycolysis are the reactions catalyzed by hexokinase, phosphofructokinase, and pyruvate kinase.

Which reactions are the control points in glycolysis?

The reactions catalyzed by hexokinase, phosphofructokinase, glyceraldehyde-3-phosphate dehydrogenase, phosphoglycerokinase, and pyruvate kinase.

Which reactions in glycolysis are coupled reactions?

The steps catalyzed by hexokinase, phosphofructokinase, and pyruvate kinase.

Which steps in glycolysis are physiologically irreversible?

The reactions are catalyzed by pyruvate dehydrogenase, citrate synthase, isocitrate dehydrogenase, and alpha-ketoglutarate dehydrogenase.

Which steps of aerobic metabolism of pyruvate through the citric acid cycle are control points?

Three reactions of glycolysis are irreversible under physiological conditions. They are the production of pyruvate and ATP from phosphoenolpyruvate, the production of fructose-1,6-bisphosphate from fructose-6-phosphate, and the production of glucose-6-phosphate from glucose. These reactions are bypassed in gluconeogenesis differ from those of glycolysis at these points and are catalyzed by different enzymes.

Which steps of glycolysis are irreversible? What bearing does this observation have on the reactions in which gluconeogenesis differs from glycolysis?

2 aspects are involved here (A) very rarely, if ever, are in vivo concentrations standard concentrations standard concentrations; actual delta G (not delta G knot) values are very dependent on local concentrations, especially if the number of reactant molecules and product molecules is not the same. (B) Values of delta G knot rigorously apply only to closed systems, however, are open systems and do not reach equilibrium, you would be dead. Metabolic pathways themselves are interconnected, including processes that take in materials from the surroundings and release waste products to the surroundings.

Why are delta G knot values not rigorously applicable to biochemical systems?

Furanoses and pyranoses have 5-membered and 6-membered rings, respectively. It is well known from organic chemistry that rings of this size are more stable and the most readily formed.

Why are furanoses and pyranoses the most common cyclic forms of sugars?

Thioesters are high energy compounds because they easily dissociate into stable reaction products. In general, the more stable the products of a reaction, the less energy is required for the reaction to proceed and the more energy is released during the course of the reaction.

Why are thioesters considered high-energy compounds?

GTP is equivalent to ATP because an enzyme, nucleoside diphosphate kinase, is able to interconvert GTP and ATP.

Why can we say that production of a GTP is equivalent to production of an ATP?

Many compounds can form acetyl-CoA, such as fats, carbohydrates, and many amino acids. Acetyl-CoA can also form fats and ketone bodies, as well as feed directly into the citric acid cycle.

Why is acetyl-CoA considered the central molecule of metabolism?

Having 2 control mechanisms allows for fine-tuning of control and for the possibility of amplification. Both mechanisms are capable of rapid response to conditions, milliseconds in the case of allosteric control and seconds to minutes in the case of covalent modification.

Why is it advantageous for two control mechanisms-allosteric control and covalent modification-to be involved in the metabolism of glycogen?

Glucose-6-phosphate is already phosphorylated. This saves one ATP equivalent in the early stages of glycolysis.

Why is it advantageous that breakdown of glycogen gives rise to glucose-6-phosphate rather than to glucose?

It can be usefu for polysaccharides to have a number of ends, characteristic of a branched polymer, rather than the two ends of a linear polymer. This would be the case when it is necessary to release residues from the ends as quickly as possible. Polysaccharides achieve this by having 1 --> 4 and 1 --> 6 glycosidic linkages to a residue at a branch point.

Why is it advantageous that polysaccharides can have branched chains? How do they achieve this structural feature?

These two pathways occur in the same cellular compartment, and , if both are on at the same time, a futile ATP hydrolysis cycle results. Using the same mechanism to turn them on/off or off/on is highly efficient.

Why is it essential that the mechanisms that activate glycogen synthesis also deactivate glycogen phosphorylase?

Many endergonic reactions are necessary for life processes. They need a source for the energy they require, and that source is the energy released by endergonic reactions.

Why is it important that energy released by exergonic reactions can be used to provide energy for endergonic reactions?

The usual thermodynamic standard state refers to pH = 0. This is not very useful in biochemistry.

Why is it necessary to define a modified standard state for biochemical applications of thermodynamics?

Bacteria that have a glyoxylate cycle can convert the acetic acid to amino acids, carbohydrates, and lipids, but humans can use the acetic acid only as an energy source or to make lipids.

Why is it possible for bacteria to survive on acetic acid as a sole carbon source, but not human beings?

Exerting control at the end of a pathway is a good example of feedback control, so it is reasonable to expect it.

Why is it reasonable to expect that control can be exerted near the end of a pathway as well as near the beginning?

the ester bond is more easily broken than any of the other bonds that form the sugar ring. Hydrolysis of that bond is the next step in the pathway.

Why is it reasonable to expect that glucose-6-phosphate will be oxidized to a lactone rather than an open-chain compound?

The enzyme that catalyzes addition of glucose residues to a growing glycogen chain cannot form a bond between isolated glucose residues; thus we have a primer.

Why is it useful to have a primer in glycogen synthesis?

PEP is a high energy compound because energy is released upon its hydrolysis, owing to the resonance stabilization of the inorganic phosphate released and the possible keto-enol tautomerization of its product, pyruvate.

Why is phosphoenolpyruvate a high energy compound?

The NADH and FADH2 produced by the citric acid cycle are the electron donors in the electron transport chain linked to oxygen. Because of this connection, the citric acid cycle is considered part of aerobic metabolism.

Why is the citric acid cycle considered part of aerobic metabolism, even though molecular oxygen does not appear in any reaction?

Fructose-1,6-bisphosphate can only undergo the reaction of glycolysis. The components of the pathway up to this point can have other metabolic fates.

Why is the formation of fructose-1,6-biphosphate the committed step in glycolysis?

The formation of fructose-1,6-biphospahet is the committed step in glycolytic pathway. It is also one of the energy requiring steps of the pathway. Control is exercised here.

Why is the formation of fructose-1,6-bisphosphate a step in which control is likely to be exercised in the glycolytic pathway?

Chitin is a suitable material for the exoskeleton of invertebrates because of its mechanical strength. Individual polymer strands are cross-linked by hydrogen bonding, accounting for the strength. Cellulose is another polysaccharide cross-linked in the same way, and it can play a similar role.

Why is the polysaccharide chitin a suitable material for the exoskeleton of invertebrates such as lobsters? What other sort of material can play a similar role?

An activation step leads to an exergonic next step in a pathway. It is similar to the way in which organic chemists want to attach a good leaving group for the next step in a series of reactions.

Why is the process of activation a useful strategy in metabolism?

A condensation reaction is one in which a new carbon-carbon bond is formed. The reaction of acetyl-CoA and oxaloacetate to produce citrate involves the formation of such a carbon-carbon bond.

Why is the reaction catalyzed by citrate synthase considered a condensation reaction?

Isozymes allow for subtle control of the enzyme to respond to different cellular needs. For example, in the liver, lactate dehydrogenase is most often used to convert lactate to pyruvate, but the reaction is often reversed in the muscle. Having different isozyme in the muscle and the liver allows for those reactions to be optimized.

Why would enzymes be found as isozymes?

Enzymes, like all catalysts, speed up the forward and reverse reaction to the same extent. Having different catalysts is the only way to ensure independent control over the rates of the forward and reverse process.

Why would you expect to see the reactions of substrate cycles involve different enzymes for different directions?

The reaction involves an achiral molecule (citrate) being converted to a chiral one (iso-citrate)

With respect o steorochemistry, what is unique about the reaction catalyzed by aconitase?

The disaccharide sucrose can be hydrolyzed to glucose and fructose, which can both be readily converted to glucose-1-phosphate, the intermediate precursor of glycogen. This is not the usual form of "glycogen-loading"

Would eating candy bars, high in sucrose rather than complex carbohydrates, help build up glycogen stores?

Probably not, because the sugar spike initially results in a rapid increase in insulin levels, which results in lowering blood glucose levels and increased glycogen storage in the liver.

Would it be advantageous to consume a candy bar with a high refined-sugar content immediately before you start a strenuous hike?

There is a large increase in entropy accompanying the hydrolysis of one molecule to five separate molecules.

Would you expect an increase or a decrease of entropy to accompany the hydrolysis of phosphatidylcholine to the constituent parts (glycerol, 2 fatty acids, phosphoric acid, and choline)? Why?

Cross-linking can be expected to play a role in the structures of polysaccharides where mechanical strength is an issue. Examples include cellulose and chitin. These crosslinks can be readily formed by extensive hydrogen bonding.

Would you expect cross-linking to play a in the structure of polysaccharides? If so, how would the cross-link be formed?

Thioesters are "high-energy" compounds that play a role in group-transfer reactions; consequently, their delta G knot of hydrolysis is large and negative to provide energy for the reaction.

Would you expect delta G knot for the hydrolysis of a thioester to be (A) large and negative, (B) large and positive, (C) small and negative, or (D) small and positive? Why?

The biosynthesis s of protein is endergonic and is accompanied by a large decrease in entropy.

Would you expect the biosynthesis of a protein from the constituent amino acids in an organism to be an exergonic or endergonic process? Why?

The citric acid cycle is less active when a cell has a high ATP/ADP ratio and a high NADH/NAD+ ratio. Both ratios indicate a high "energy charge" in the cell, indicating less of a need for the energy-releasing reactions of the citric acid cycle.

Would you expect the citric acid cycle to be more or less active when a cell has a high ATP/ADP ratio and a high NADH/NAD+ ratio? Why?

The synthesis of sugars by plants in photosynthesis is endergonic and requires light energy from the sun.

Would you expect the production of sugars by plants in photosynthesis to be an exergonic or endergonic process? Why?

Iodine is the reagent that will be added to the reaction mixture in the titration. When the end point is reached, the next drop of iodine will produce a characteristic blue color in the presence of the indicator.

You are a teaching assistant in a general chemistry lab. The next experiment is to be an oxidation-reduction titration involving iodine. You get a starch indicator from the stockroom. Why do you need it?

Eating high-carbohydrate foods for several days before strenuous activity is intended to build up glycogen stores in the body. Glycogen will be available to supply required energy.

You are planning to go on a strenuous hike and are advised to eat plenty of high-carbohydrate foods, such as bread and pasta, for several days beforehand. Suggest a reason for the advice.

Electron transport

(to oxygen) A series of oxidation-reduction reactions by which the electrons derived from oxidation of nutrients are passed to oxygen.

disaccharides

2 monosaccharides (monomeric sugars) linked by a glycosidic bond.

Converting a sugar to an epimer requires inversion of configuration at a chiral center. This can be done only by breaking and reforming covalent bonds.

2 sugars are epimers of each other. Is it possible to convert one to the other without breaking covalent bonds?

The entire pathway can be looked at as a large coupled reaction. Thus, if the overall pathway has a negative delta G, an individual step may be able to have a positive delta G, and the pathway can still continue.

4 reactions have a positive delta G values. How can this be explained?

Fischer projection

A 2D representation of the stereochemistry of 3D molecules.

Biotin

A CO2 carrier molecule

Redox reactions. NAD+, or NADPH in an anabolic process, would likely be used. FAD probably would not be used because its free energy change is too low.

A biochemical reaction transfer 60 kJ mol^-1 (15 kcal mol^-1) of energy. What general process most likely would be involved in the transfer? What cofactor (or co-substrate) likely would be used? Which cofactor would not be used?

Glcosidic bond

A bond between a sugar and another molecule.

Citric acid cycle

A central metabolic pathway; part of aerobic metabolism

Thiamine pyrophosphate

A coenzyme involved in the transfer of two-carbon units.

glycoside

A compound in which one or more sugars is bonded to another molecule.

hemiketal

A compound that is formed by reaction of a ketone with an alcohol and is found in the cyclic structure of sugars.

hemiacetal

A compound that is formed by reaction of an aldehyde with an alcohol and is found in the cyclic structure of sugars.

Pyranose

A cyclic form a sugar containing a 6 membered ring; it named for its resemblance to pyran.

Furanose

A cyclic sugar with a 5 membered ring, named for its resemblance to the ring system in furan.

Milk contains lactose. many people are sensitive to lactose and require an alternative beverage.

A friend asks you why some parents at her child's school want to choice of beverages served at lunch, rather than milk alone. What do you tell your friend?

Creatine phosphate can phosphorylate ADP to ATP. there is a biochemical "germ of truth" here, but the effectiveness of such a supplement is another matter.

A friend has seen creatine supplements for sale in a health-food store and asks why. What do you tell your friend?

state function

A function that depends only on the initial and final states of a system, not on the path between the states.

Pyruvate dehydrogenase complex

A multi-enzyme complex that catalyzes the conversion of pyruvate to acetyl-CoA and carbon dioxide.

coenzyme

A non-protein substance that takes part in an enzymatic reaction and is regenerated at the end of the reaction.

Glyoxylate cycle

A pathway in plants that is an alternative to the citric acid cycle and that bypasses several citric acid cycle reactions.

Pentose phosphate pathway

A pathway in sugar metabolism that gives rise to five-carbon sugars and NADPH.

Haworth projection formulas

A perspective representation of the cyclic forms of sugars

Pectin

A polymer of galacturonic acid; it occurs in the cell walls of plants.

glycogen

A polymer of glucose; an important energy storage molecule in animals.

cellulose

A polymer of glucose; an important structural material in plants.

polysaccharide

A polymer of sugars.

peptidoglycan

A polysaccharide that contains peptide crosslinks; it is found in bacterial cell walls.

Oxidative phosphorylation

A process for generating ATP; it depends on the creation of a pH gradient within the mitochondrion as a result of electron transport.

Non-heme iron protein

A protein that contains iron and sulfur but no heme group; also known as iron-sulfur protein.

Substrate-level phosphorylation

A reaction in which the source of phosphorus is inorganic phosphate ion, not ATP.

Anaplerotic reaction

A reaction that ensures an adequate supply of an important metabolite.

It is unlikely that this finding will be confirmed by other researchers. the highly branched structure of glycogen is optimized for release of glucose on demand.

A researcher claims to have discovered a variant form of glycogen. The variation is that it has very few branches (every 50 glucose residues or so) and that the branches are only three residues long. Is it likely that this discovery will be confirmed by later work?

Oxidizing agent

A substance that accepts electrons from other substances .

Reducing agent

A substance that gives up electrons to other substances.

ketose

A sugar that contains a ketone group as part of its structure.

aldose

A sugar that contains an aldehyde group as part of its structure

Thioester

A sulfur-containing analogue of an ester.

The fact that a reaction is thermodynamically favorable does not mean that it will occur biologically. Even though there appears to be ample energy to catalyze the production of 2 ATPs from PEP, there is no enzyme that catalyzes this reaction.

A very favorable reaction is the production of ATP and pyruvate from ADP and phosphoenolpyruvate. Given the standard free-energy change for this coupled reaction, why does the following reaction not occur? PEP + 2ADP --> Pyruvate + 2ATP

There is an adenine nucleotide portion in the structure of NADH, with a specific binding site on NADH-linked dehydrogenases for this portion of NADH

ATP is a competitive inhibitor of NADH binding to malate dehydrogenase, as are ADP and AMP. Suggest a structural basis for this inhibition.

Amphibolic

Able to be a part of both anabolism and catabolism.

The energy released by hydrolysis of acetyl-CoA is needed for the condensation reaction that links the acetyl moiety to oxaloacetate, yielding citrate. The energy released by hydrolysis of succinyl-CoA drives the phosphorylation of GDP, yielding GTP.

Acetyl-CoA and succinyl-CoA are both high energy thioesters, but their chemical energy is put to different uses. Why is this so?

The ATP constantly generated by living organisms is used as a source of chemical energy for endergonic processes. there is a good deal of turnover of molecules, but no net charge.

Adult humans synthesize large amounts of ATP in the course of a day, but their body weights do not change significantly. In the same time period, the structures and compositions of their bodies also do not change appreciably. Explain this apparent contradiction.

Glucose and fructose

Advertisements for a food supplement to be taken by athletes claimed that the energy bars contained the 2 best precursors of glycogen. What were they?

The concentration of reducing groups is too small to detect.

All naturally occurring polysaccharides have 1 terminal residue, which contains a free anomeric carbon. Why do these polysaccharides not give a positive chemical test for reducing sugar?

lactate dehydrogenase

An NADH-linked dehydrogenase that catalyzes the conversion of pyruvate to lactate.

To 2500, one place (0.02%). To 1000, four places (0.08%). To 200, 24 places (0.48%).

An amylose chain is 500 glucose units long. At how many places must it be cleaved to reduce the average length to 2500 units? To 1000 units? To 200 units? What percentage of the glycosidic links are hydrolyzed in each case? (Even partial hydrolysis can drastically alter the physical properties of polysaccharides and thus affect their structural role in organisms)

half reaction

An equation that shows either the oxidative or the reductive part of an oxidation-reduction reaction.

Glyceraldehyde-3-phosphate dehydrogenase

An important enzyme in glycolysis and gluconeogenesis

From the point at which aldolase splits fructose-1,6-bisphosphate into dihydroxyacetone phosphate and glyceraldehyde-3-phosphate; all reactions of the pathway are doubled (only the path from 1 glyceraldehyde-3-phosphate is usually shown)

At what point in glycolysis are all the reactions considered doubled?

Of the 3 processes-glycogen formation, gluconeogenesis, and the pentose phosphate pathway-only one, gluconeogenesis, involves an enzyme that requires biotin. The enzyme in question is pyruvate carboxylase, which catalyzes the conversion of pyruvate to oxaloacetate, an early step in gluconeogenesis.

Avidin, a protein found in egg whites, binds to biotin so strongly that in inhibits enzymes that require biotin. What is the effect of avidin on glycogen formation? On gluconeogenesis? O the pentose phosphate pathway?

Glycosidic bonds can be formed between the side chain hydroxyls of serine or threonine residues and the sugar hydroxyls. In addition, there is the possibility of ester bonds forming between the side chain carboxyl groups of aspartate or glutamate and the sugar hydroxyls.

Based on what you know about glycosidic bonds, propose a scheme for formation of covalent bonds between the carbohydrate and protein portions of glycoproteins.

Thiamine pyrophosphate is a coenzyme required in the reaction catalyzed by pyruvate carboxylase. Because this reaction is a part of the metabolism of ethanol, less will be available to serve as a coenzyme in the reactions of other enzymes that require it.

Beriberi is a disease caused by a deficiency of vitamin B1 (thiamine) in the diet. Thiamine is the precursor of thiamine pyrophosphate. In view of what you have learned in chapter 17, why is it not surprising that alcoholics tend to develop this disease?

Heparin is an anticoagulant. Its presence prevents blood clotting.

Blood samples for research or medical tests sometimes have heparin added. Why is this done?

Lipoic acid plays a role in both the redox and in acetyl transfer reactions.

Briefly describe the dual role of lipoic acid in the pyruvate dehydrogenase complex.

The sugar portions of the blood group glycoproteins are the source of the antigenic difference.

Briefly indicate the role of glycoproteins as antigenic determinants for blood groups.

Research is in progress to modify pyruvate kinase isozymes typical of cancer cells to resemble those of normal cells. the goal is to redirect metabolism to that of normal cells, rather than cancer cells.

Can modification of enzymes of aerobic glycolysis play a role in cancer treatment?

No, there is no relationship between the thermodynamic quantity delta G knot and the speed. The delta G knot reflects the thermodynamic possibly under standard states. Speed is a kinetic quantity that is based on the ability of an enzyme to catalyze the reaction and the real substrate concentrations in the cell.

Can the thermodynamic property delta G knot be used to predict the speed of a reaction in a living organism? Why or why not?

Yes, if you correct for the difference in temperature and concentrations from the standard values.

Can you use the equation delta G knot = -RTInKeq to get the delta G knot from the reaction, Glucose-6-phosphate + H2O ---> Glucose + Pi, Keq = (glucose x Pi)/(glucose-6-P). The delta G knot prime = -20.9 kJ mol^-1. The Keq at pH 8.5 and 38 C is 122.

This is possible, and it is done. these poisons also affect other tissues, including skin, hair, cells of the intestinal lining, and especially the immune system and red blood cells. People on chemotherapy are usually more susceptible to infectious diseases than healthy people and are often somewhat anemic.

Cancer cells grow so rapidly that they have a higher rate of anaerobic metabolism than most body tissues, especially in center of a tumor. Can you use drugs that poison enzymes of anaerobic metabolism in the treatment of cancer? Why or why not?

It is intermediate; thus, ATP is ideally positioned to serve as a phosphate donor or (as ADP) a phosphate acceptor, depending on local concentrations.

Comment on the free-energy of hydrolysis of the phosphate bond of ATP (-30.5 kJ mol^-1; -7.3 kcal mol^-1) relative to those other organophosphates (e.g. sugar phosphates, creatine phosphates)

The local decrease in entropy associated with living organisms is balanced by the increase in the entropy of the surroundings caused by their presence. Coupling of reactions leads to overall dispersal of energy in the Universe.

Comment on the statement that the existence of life is a violation of the 2nd law of thermodynamics, adding concepts from chapter 15 to those we saw in chapter 1.

The sequence of monomers in a polysaccharide is not generically coded, and , in this sense, it does not contain information, as is the case with amino acids in a protein.

Compare the information in the sequence of monomers in a polysaccharide with that in the sequence of amino acid residues in a protein.

monosaccharides

Compounds that contain a single carbonyl group and two or more hydroxyl groups

The levels of substrates and products can affect the true delta G of a reaction, changing it form zero to a high number as in part (A). Delta G is negative when there is a larger amount of substrate than product.

Consider the reaction A <---> B + C, where delta G knot = 0.00, and the same reaction of D + E <---> F where the concentrations are 1 M, 10^-3 M, and 10^-6M. How does the delta G value compare with the reaction G <--> H (1 M and 10^-3 M)? What do the different delta G's tell you about the influence of concentrations of reactants and products on reactions?

-50 kJ assuming 298 K

Consider the reaction A <---> B + C, where delta G knot = 0.00. (A) What is the value of delta G (not delta G knot) when the initial concentrations of A, B, and C are 1 M, 10^-3 M, and 10^-6 M.

-20 kJ assuming 298 K

Consider the reaction A <---> B + C, where delta G knot = 0.00. (B) What is delta G (not delta G knot) for the reaction D + E <---> F, concentrations are 1 M, 10^-3 M, 10^-6 M.

-20 kJ assuming 298 K

Consider the reaction A <---> B + C, where delta G knot = 0.00. (C) What is the delta G (not delta G knot) for the reaction G <---> H, where the concentrations are 1 M and 10^-3 M.

The information given here deals with the thermodynamics of the reaction, not the kinetics. It is not possible to predict the rate of the reaction.

Consider the reaction; Glucose-6-phosphate + H2O ---> Glucose + Pi, Keq = (glucose x Pi)/(glucose-6-P). The Keq at pH 8.5 and 38 C is 122. Can you determine the rate of the reaction from this information.

Arabinose is an epimer of ribose. Nucleosides in which arabinose is substituted for ribose act as inhibitors in reactions of ribonucleosides.

Consider the structures of arabinose and ribose. Explain why nucleotide derivatives of arabinose, such as ara-C and ara-A, are effective metabolic poisons.

Bacterial cell walls are not likely to consist largely of protein. The polysaccharides that comprise the cell walls are required to provide sufficient mechanical strength necessary for the structure integrity of the cell walls.

Could bacterial cell walls consist largely of protein? Why or why not?

Isozymes are oligomeric enzymes that have slightly different amino acid composition in different organs. Lactate dehydrogenase is an example, as is phosphofructokinase.

Define isozymes and give an example from the material discussed in chapter 17.

The free energy of hydrolysis of a substrate is the energetic driving force in substrate-level phosphorylation. An example is the conversion of glyceraldehyde-3-phosphate to 1,3-bisphosphoglycerate.

Define substrate level phosphorylation and give an example from the reactions discussed in chapter 17.

"Going for the burn" in a workout refers to the sensation that accompanies lactic acid buildup. This is turn arises from anaerobic metabolism of glucose in muscle.

Describe "going for the burn" in a workout in terms found in chapter 18.

PDH is controlled allosterically. It is inhibited by ATP, acetyl-CoA, and NADH. In addition, it is subject to control by phosphorylation. When PDH kinase phosphorylates PDH, it becomes inactive. Removing the phosphate with the PDH phosphate reactivates it.

Describe the multiple ways that PDH is controlled.

The citric acid cycle is the central metabolic pathway and indirect producer of energy. It receives fuels from the other pathways at many points and generates reduced electron carriers that go into the electron transport chain. It is also involved in anabolism, as many of its intermediates can be drawn off to synthesize other compounds.

Describe the purposes of the citric acid cycle.

In xidative decarboxylation, the molecule that is oxidized loses a carboxyl group as carbon dioxide. Examples of oxidative decarboxylation include the conversion of pyruvate to acetyl-CoA, isocitrate to alpha-ketoglutarate, and alpha-ketoglutarate to succinyl-CoA.

Discuss oxidative decarboxylation, using a reaction from chapter 19 to make the point.

ATP is an inhibitor of several steps of glycolysis as well as other catabolic pathways. The purpose of catabolic pathways is to produce energy, and high levels of ATP mean the cell already has sufficient energy. Glucose-6-phosphate inhibits hexokinase and is an example of product inhibition. If the glucose-6-phosphate level is high it may indicate that sufficient glucose is available from glycogen breakdown or that the subsequent enzymatic steps of glycolysis are going slowly. Either way, there is no reason to produce more glucose-6-phosphate. Phosphofructokinase is inhibited by a special effector molecule, fructose-2,6-bisphosphate, whose levels are controlled by hormones. It is also inhibited by citrate, which indicates that there is sufficient energy from the citric acid cycle, probably from fat and amino acid degradation. Pyruvate kinase is also inhibited by acetyl-CoA, the presence of which indicates that fatty acids are being used to generate energy from the citric acid cycle. When these carbon skeletons can come from other sources, glycolysis is inhibited to spare glucose for other purposes.

Discuss the logic of the nature of the allosteric inhibitors and activators of glycolysis. Why would these molecule be used?

Thiamine pyrophosphate is a coenzyme I the transfer of 2 carbon units. It is required for catalysis by pyruvate decarboxylase in alcoholic fermentation.

Discuss the role of thiamine pyrophosphate in enzymatic reactions, using material from chapter 17 to illustrate your point.

Hormones exercise another level of control over metabolism, beyond that of allosteric and feedback control. Glycolysis can certainly be affected in this manner. The effect of insulin on carbohydrate metabolism is well known.

Do hormones play a role in control of metabolism? Is glycolysis a possible pathway for such control?

Only a portion of the energy is released by exergonic reactions drives endergonic reactions. An example is the exergonic oxidation of glucose to two lactate ions, which releases 184.5 kJ for each mole of glucose. This reaction is coupled to the phosphorylation of 2 ADP to 2 ATP, an endergonic reaction that requires 61 kJ for each mole of glucose. The 2 amounts of energy are not the same.

Does all the energy released by an exergonic reaction go into driving a coupled endergonic reaction? Give an example.

There is a net gain of 3, rather than 2, ATP when glycogen, not glucose, is the staring material of glycolysis.

Does the net gain of ATP in glycolysis differ when glycogen, rather than glucose, is the starting material? If so, what is the change?

The oxidation of glucose to carbon dioxide and water takes place in many steps. This arrangement allows for use of the coenzymes involved and favors production of ATP.

Does the oxidation of glucose to carbon dioxide and water take place in one step or many?

Thiamine pyrophosphate is a cofactor necessary for the function of transketolase, an enzyme that catalyzes one of the reactions in the non-oxidative part off the pentose phosphate pathway.

Does thiamine pyrophosphate play a role in the reactions of the pentose pathway? If so, what is that role?

Substrate cycle are futile in the sense that there is no net change except for the hydrolysis of ATP. However, substrate cycles allow for increased control over opposing reactions when they are catalyzed by different enzymes.

Earlier biochemists called substrate cycles "futile cycles". Why might they have chosen such a name? Why is it something of a misnomer?

Debranching enzymes

Enzymes that hydrolyze the linkages in a branched-chain polymer such as amylopectin.

Fructose-2,6-bisphosphate is an allosteric activator of phosphofructokinase (a glycolytic enzyme) and an allosteric inhibitor of fructose-1,6-bisphosphatase (and enzyme in the pathway of gluconeogenesis). It thus play a role in 2 pathways that are not exactly the reverse of each other.

Explain how fructose-2,6-bisphosphate can play a role in more than one metabolic pathway.

Differences in structure: cellulose consists of linear fibers, but starch has a coil form. Differences in function: cellulose has a structural role, but starch is used for energy storage.

Explain how the minor structural difference between alpha and beta glucose is related to the differences in structure and function in the polymers formed from these 2 monomers.

If a cell needs NADPH, all the reactions of the pentose phosphate pathway tak place. If a cell needs ribose-5-phosphate, the oxidative portion of the pathway can be bypassed; only the non-oxidative reshuffling reactions take place. the pentose phosphate pathway does not have a significant effect on the cell's supply of ATP.

Explain how the pentose phosphate pathway can respond to a cell's need for ATP, NADPH, and ribose-5-phosphate.

Aldolase catalyzes the reverse aldol condensation of fructose-1,6-bisphosphate to glyceraldehyde-3-phosphate and dihydroxyacetone phosphate.

Explain the origin of the name of the enzyme aldolase.

Coenzyme A serves several purposes. It is a high energy compound, activating the initial steps of the metabolic pathway. It is used as a tag to "earmark" a molecule for a particular pathway. It is large and cannot cross membranes, so compartmentalization of pathways can be affected by binding metabolites to coenzyme A.

Explain why several biochemical pathways start by putting a coenzyme A onto the molecule that initiates the pathway.

Delta G knot prime = delta H knot prime - T delta S knot prime and delta S knot prime = 34.9 J mol^-1 K^-1 = 8.39 cal mol^-1 K^-1. There are two particles on the reactant side of the equation and three on the product side, representing an increase in disorder.

For the hydrolysis of ATP at 25 C (298 K) and pH 7, ATP + H2O --> ADP + Pi + H+, the standard free energy of hydrolysis (delta G knot) is -30.5 kJ mol^-1 (-4.8 kcal mol^-1). Calculate the standard entropy change (delta S knot) for the reaction, in both joules and calories. Why is the positive sign of the answer to be expected in view of the nature of the reaction?

It is important to have two different pools of redox coenzymes. In the cytosol, the NAD+/NADH ratio is high, but the NADPH/NADP+ ratio is also high. This means that anabolic reactions can take place in the cytosol, while catabolic reactions, such as glycolysis, can also take place. If there were not 2 different pools of these coenzymes, no single cell location could have both catabolism and anabolism. Having 2 different, but structurally related, reducing agents help keep anabolic and catabolic reactions distinct from each other.

Give a reason why catabolic pathways generally produce NADH and FADH2, whereas anabolic pathways generally use NADPH.

We have previously encountered substrate-level phosphorylation in glycolysis. An example is the transfer of a phosphate from 1,3-bisphosphoglycerate to ADP to afford 3-phosphoglycerate and ATP.

Give an example of substrate level phosphorylation in a pathway other than the citric acid cycle.

Because of the branching, the glycogen molecule gives rise to a number of available glucose molecules at a time when it is being hydrolyzed to provide energy. A linear molecule could produce only one available glucose at a time.

Glycogen is highly branched. What advantage, if any, does this provide an animal?

Proteoglycans

Glycoproteins with a high carbohydrates content.

Furanosides

Glycosides involving a anose

Pyranosides

Glycosides involving a pyranose.

Glucose-6-phosphate inhibits hexokinase, the enzyme responsible for its own formation. Because G-6-P is used up by additional reactions of glycolysis, the inhibition is relieved.

High levels of glucose-6-phosphate inhibit glycolysis. If the concentration of glucose-6-phosphate decreases, activity is restored. Why?

Different control mechanisms have inherently different time scales. Allosteric control can take place in milliseconds, whereas covalent control takes seconds to minutes. Genetic control has a longer time scale than either.

How can different time scales for response be achieved in control mechanisms?