Biochemistry Principles of Metabolic Regulation

Which type of mechanism is NOT known to play a role in the reversible alteration of enzyme activity? A) activation by cleavage of an inactive zymogen B) allosteric response to a regulatory molecule C) alteration of the synthesis or degradation rate of an enzyme D) covalent modification of the enzyme E) interactions between catalytic and regulatory subunits

A

Glycogen is converted to monosaccharide units by: A) glucokinase. B) glucose-6-phosphatase C) glycogen phosphorylase. D) glycogen synthase. E) glycogenase.

C

Which method of directly regulates PFK-I? A) feedback inhibition by fructose 2,6-bisphosphate B) feed forward activation by phosphoenolpyruvate C) allosteric activation by AMP D) its phosphorylation in response to glucagon signaling E) allosteric activation by citrate

C

Which substance activates glycogen synthase b in liver? A) glucagon B) insulin C) glucose 6-phosphate D) both insulin and glucose 6-phosphate E) both glucagon and glucose 6-phosphate

D

Which process is NOT an event in the signaling pathway from insulin to glycogen synthase kinase 3 (GSK3) inactivation? A) insulin binding to a tyrosine kinase receptor B) activation of insulin receptor substrate-1 (IRS-1) by phosphorylation C) phosphatidylinositol 3-kinase associating with IRS-1 generates phosphatidylinositol 3,4,5-triphosphate D) protein kinase B being activated by a protein kinase known as PDK-1 E) protein kinase B phosphorylating GSK3, resulting in its activation

E

Which tissue has the FASTEST average rate of protein turnover? A) the heart B) the brain C) the kidneys D) skeletal muscle E) the liver

E

Show the reaction catalyzed by glycogen synthase.

The reaction is the addition of a glucose moiety from UDP-glucose to the nonreducing end of a glycogen chain; the linkage formed is (α1 → 4). (See Fig. 15-32.)

Diagram the pathway from glucose to glycogen; show the participation of cofactors and name the enzymes involved.

(1) Glucose + ATP ⎯⎯⎯⎯→ glucose 6-phosphate + ADPcatalyzed by hexokinase(2) Glucose 6-phosphate ⎯⎯⎯⎯→ glucose 1-phosphatecatalyzed by phosphoglucomutase(3) Glucose 1-phosphate + UTP ⎯⎯⎯⎯→ UDP-glucose + PPicatalyzed by UDP-glucose pyrophosphorylase(4) UDP-glucose ⎯⎯⎯⎯→ glycogen + UDPcatalyzed by glycogen synthase

Many of the steps in the pathways described in this chapter are essentially irreversible (for A ® B DG << 0). As a result, if the cell wants to carry out the reverse transformation, it must use a different pathway to go from B ® A. For each of the enzymes on the left, pick the enzyme on the right that carries out the reverse transformation (not necessarily the reverse reaction). a) hexokinase 1) glycogen phosphorylase b) fructose 1,6-bisphosphatase 2) pyruvate carboxylase & PEP carboxylase c) glycogen synthase 3) phosphofructokinase I d) pyruvate kinase 4) glucose-6-phosphatase

(a)-(4); (b)-(3); (c)-(1); (d)-(2)

Epinephrine binding to b-adrenergic receptors on hepatocytes causes the eventual activation of protein kinase A. Which enzyme is NOT a substrate for protein kinase A? A) phosphorylase b B) phosphorylase b kinase C) glycogen synthase D) phosphofructokinase-2 E) pyruvate kinase

A

Is glycogen phosphorylase activated, inhibited, or unaffected in response to a glucagon signal in liver tissue? A) activated B) inhibited C) unaffected

A

Mutating which proteins is unlikely to result in a glycogen storage disease? A) pyruvate carboxylase B) GLUT2 C) phosphorylase D) PFK-1 in muscle E) phosphorylase kinase

A

The MOST sensitive indicator of the energetic status of the cell is the concentration of: A) AMP. B) ADP. C) ATP. D) cAMP. E) glucose.

A

Which enzyme is used in both glycolysis and gluconeogenesis? A) 3-phosphoglycerate kinase B) hexokinase C) glucose 6-phosphatase D) phosphofructokinase-2 E) pyruvate kinase

A

Which factor is NOT involved in up-regulating the transcription of glycolytic or gluconeogenic enzymes? A) phosphofructokinase-2 B) carbohydrate response element binding protein C) sterol response element binding protein D) cAMP response element binding protein E) FOXO1

A

Which isozyme of lactate dehydrogenase has the LOWEST Km value for the oxidation of lactate in cardiac tissue? A) LDH1 B) LDH2 C) LDH3 D) LDH4 E) LDH5

A

Which statement describes a possible fate for glucose 1-phosphate in skeletal muscle? A) Glucose 1-phosphate can enter glycolysis after conversion to glucose 6-phosphate. B) Glucose 1-phosphate cannot enter the pentose phosphate pathway after conversion to glucose 6-phosphate. C) Glucose 1-phosphate can be used to replenish blood glucose. D) Glucose 1-phosphate can be used to replenish blood glucose or enter glycolysis after conversion to glucose 6-phosphate. E) All of the answers are correct.

A

Which statement is NOT associated with controlling the rate of glycogen synthesis in hepatocytes? A) Insulin stimulates the translocation of GLUT 2 transporters to the plasma membrane. B) Insulin induces the synthesis of hexokinase IV. C) Glucagon inhibits the activity of glycogen synthase via covalent modification. D) Insulin activates phosphorylase a phosphatase. E) Epinephrine and insulin both result in the phosphorylation of the glycogen targeting protein GM.

A

Which statement is TRUE for the reciprocal regulation of phosphofructokinase-1 (PFK-1) and fructose 1,6-bisphosphatase (FBPase-1)? A) Fructose 2,6-bisphosphate inhibits FBPase-1 and activates PFK-1. B) Fructose 2,6-bisphosphate inhibits PFK-1 and activates FBPase-1. C) Fructose 1,6-bisphosphate inhibits FBPase-1 and activates PFK-1. D) Fructose 1,6-bisphosphate inhibits PFK-1 and activates FBPase-1.

A

Which statement is TRUE of glycogen synthesis and breakdown? A) Phosphorylation activates the enzyme responsible for breakdown, and inactivates the synthetic enzyme. B) Synthesis is catalyzed by the same enzyme that catalyzes breakdown. C) The glycogen molecule "grows" at its reducing end. D) The immediate product of glycogen breakdown is free glucose. E) Under normal circumstances, glycogen synthesis and glycogen breakdown occur simultaneously and at high rates.

A

Which statement regarding regulation of glycolysis and gluconeogenesis is FALSE? A) Phosphofructokinase-1 and fructose 1,6-bisphosphatase are prevented from forming a futile cycle by reversible covalent modification. B) Hexokinase IV and glucose 6-phosphatase are transcriptionally regulated in hepatocytes. C) Phosphofructokinase-1 and fructose 1,6-bisphosphatase are reciprocally regulated by the allosteric regulator, fructose 2,6-bisphosphate. D) Binding of fructose 2,6-bisphosphate to phosphofructokinase-1 reduces the affinity of this enzyme for citrate. E) The cellular concentration of fructose 2,6-bisphosphate is determined by a bifunctional enzyme that is hormonally regulated.

A

What is a "futile cycle"? Give an example of a potential futile cycle in carbohydrate metabolism, and describe methods used by cells or organisms to avoid the operation of the futile cycle.

A futile cycle is a pair of reactions or pathways in one of which A is converted into B, and in the other, B into A. For example, conversion of fructose 6-phosphate into fructose 1,6-bisphosphate (catalyzed by phosphofructokinase-1) is effectively reversed by the reaction catalyzed by fructose 1,6-bisphosphatase. The sum of the two reactions is the hydrolysis of ATP and the dissipation of energy as heat, a wasteful process except when the organism needs to generate heat to maintain body temperature.Fructose 6-phosphate + ATP ⎯→ fructose 1,6-bisphosphate + ADPFructose 1,6-bisphosphate ⎯→ fructose 6-phosphate + PiSum: ATP ⎯→ ADP + Pi (+ heat)Cells use reciprocal regulation of the pathways such that when a reaction in the pathway in one direction is stimulated, the reaction in the reverse pathway is inhibited, and vice versa.

Write out the reaction catalyzed by adenylate kinase and explain why this reaction is so important in skeletal muscle.

Adenylate kinase (also known as ADK or myokinase) is a phosphotransferase enzyme that catalyzes the interconversion of adenine nucleotides (ATP, ADP, and AMP). By constantly monitoring phosphate nucleotide levels inside the cell, ADK plays an important role in cellular energy homeostasis. A phosphotransferase that catalyses the reaction ATP + AMP = 2 ADP in red cells and muscle and plays a critical role in intracellular energy homeostasis. As energy levels change under different metabolic stresses adenylate kinase is then able to generate AMP; which itself acts as a signaling molecule in further signaling cascades. This generated AMP can, for example, stimulate various AMP-dependent receptors such as those involved in glycolytic pathways, K-ATP channels, and 5' AMP-activated protein kinase Common factors that influence adenine nucleotide levels, and therefore ADK activity are exercise, stress, changes in hormone levels, and diet. Adenylate kinase is also known to interact with creatinine phosphate. Creatinine phosphate is the major source of stored

Why is citrate, in addition to being a metabolic intermediate in aerobic oxidation of fuels, an important control molecule for a variety of enzymes?

As the key biochemical intermediate in the citric acid cycle resulting from the condensation of oxaloacetate and acetyl-CoA, citrate is at a junction of amino acid, fatty acid, and pyruvate oxidation, serving as an intracellular signal that the cell's current energy needs are being met. In particular, it is an allosteric regulator of PFK-1, increasing the inhibitory effect of ATP, and further reducing the flow of glucose through glycolysis.

After ingestion of a carbohydrate-rich meal, the increased concentration of glucose in the blood is associated with many changes in the metabolism of humans. Which change would NOT be expected? A) a decrease in the secretion of glucagon from the pancreas B) an increase in glycogen phosphorolysis C) an increase in the levels of fructose 2,6-bisphosphate D) activation of phosphorylase b kinase E) All of these changes would be expected.

B

An increase in which compound leads to the dephosphorylation and activation of phosphofructokinase-2? A) glucagon B) xyulose-5-phosphate C) pyruvate D) citrate E) ADP

B

Aside from maintaining the integrity of its hereditary material, the MOST important general metabolic concern of a cell is: A) keeping its glucose levels high. B) maintaining a constant supply and concentration of ATP. C) preserving its ability to carry out oxidative phosphorylation. D) protecting its enzymes from rapid degradation. E) running all its major metabolic pathways at maximum efficiency.

B

Cellular isozymes of pyruvate kinase are allosterically inhibited by: A) high concentrations of AMP. B) high concentrations of ATP. C) high concentrations of citrate. D) low concentrations of acetyl-CoA. E) low concentrations of ATP.

B

Glucokinase (hexokinase IV) differs from hexokinase (hexokinase I): A) by having a higher affinity for glucose and not being inhibited by high levels of glucose. B) by requiring larger concentrations of glucose before reaching maximal activity. C) to allow the liver to export free glucose to the bloodstream when blood sugar levels drop. D) so that the liver does not compete with other tissues for glucose when glucose levels are high. E) to allow the pancreas to trigger insulin release when blood sugar levels are low.

B

How are the opposing pathways of glycolysis and gluconeogenesis prevented from extensive futile cycling? A) At least seven of the enzymes in the two pathways are different. B) Key enzymes are regulated in a coordinated and reciprocal manner. C) Catabolic and anabolic pathways do not take place in the same cellular compartments. D) The overall free-energy change always favors the catabolic pathway. E) Gluconeogenesis involves three endergonic bypass reactions.

B

Is glycogen phosphorylase activated, inhibited, or unaffected in response to an insulin signal in skeletal muscle? A) activated B) inhibited C) unaffected

B

The enzyme glycogen phosphorylase: A) catalyzes a cleavage of b (1 ® 4) bonds. B) catalyzes a hydrolytic cleavage of a (1 ® 4) bonds. C) is a substrate for a kinase. D) uses glucose 6-phosphate as a substrate. E) uses glucose as a substrate.

B

Which enzyme does NOT play a role in glycogen metabolism? A) glucose-6-phosphatase B) fructose 1,6-bisphosphatase C) glycosyl-(4®6) transferase D) protein phosphatase 1 E) phosphoglucomutase

B

Which factor directly results in the activation of glycogen synthase? A) binding of glucose-6-phosphate B) dephosphorylation of multiple residues by phosphoprotein phosphorylase-1 (PP1) C) phosphorylation of specific residues by casein kinase II (CKII) D) phosphorylation of specific residues by glycogen synthase kinase-3 (GSK-3) E) the presence of insulin

B

Which statement is FALSE with respect to near-equilibrium metabolic reactions? A) Near-equilibrium reactions have a free-energy change near zero. B) Near-equilibrium reactions operate nonenzymatically in vivo. C) Near-equilibrium reactions are dependent on the concentration of the products. D) Near-equilibrium reactions are not usually a control point in a metabolic pathway. E) All of the statements are false.

B

Which statement is TRUE for glycogen granules in hepatocytes? A) Hepatic glycogen granules account for approximately 1% to 2% of the weight of the liver. B) Each particle may contain up to 55,000 glucose molecules. C) Glycogen granules cluster together, forming a-rosettes that become visible after a 24-hour fast. D) All of the statements are true. E) None of the statements is true.

B

Which statement is TRUE of glycogen synthase? A) Activation of the enzyme involves a phosphorylation. B) It catalyzes addition of glucose residues to the nonreducing end of a glycogen chain by formation of (a1 ® 4) bonds. C) It uses glucose-6-phosphate as donor of glucose units D) It catalyzes addition of glucose residues at branch points by formation of (a1 ® 6) bonds. E) The enzyme has measurable activity only in liver.

B

An altered version of glycogen synthase is produced in the laboratory, with one of its amino acid residues substituted for another. Unlike normal glycogen synthase, the activity of the mutant protein is unaffected by glycogen synthase kinase-3. Which mutation is MOST likely to produce this effect? A) Cys ® Ser B) Ile ® Thr C) Ser ® Ala D) Cys ® Met E) Thr ® Ser

C

If the mass action ratio, Q, for a reaction under cellular conditions is larger than the equilibrium constant, Keq, then the reaction will: A) be at equilibrium. B) go backward and be endergonic. C) go backward and be exergonic. D) go forward and be endergonic. E) go forward and be exergonic.

C

Is glycogen phosphorylase activated, inhibited, or unaffected in response to a glucagon signal in skeletal muscle? A) activated B) inhibited C) unaffected

C

Metabolic pathways are said to operate in a steady state. Which process does NOT contribute to this? A) Most biological reactions are reversible under normal cellular conditions. B) Key reactions at the beginning and end of a pathway are often regulated synchronously. C) Catabolic pathways are active when cellular energy levels are low. D) Reversible reactions proceed to equilibrium.

C

Starting from glucose, what is the net number of NTP molecules used in the synthesis of glycogen? A) zero B) one C) two D) three E) four

C

The glycogen-branching enzyme catalyzes: A) degradation of (a1 ® 4) linkages in glycogen B) formation of (a1 ® 4) linkages in glycogen. C) formation of (a1 ® 6) linkages during glycogen synthesis. D) glycogen degradation in tree branches. E) removal of unneeded glucose residues at the ends of branches.

C

To which enzyme in glycolysis is phosphoglucomutase MOST similar? A) phosphohexose isomerase B) triosphosphate isomerase C) phosphoglycerate mutase D) enolase E) phosphoglycerate kinase

C

What will be the net yield of ATP (per glucose unit) starting from glycogen and ending at pyruvate? A) 1 ATP B) 2 ATP C) 3 ATP D) 4 ATP E) 5 ATP

C

Which enzyme-catalyzed reaction is MOST sensitive to changes in the concentration of its reactants under physiological conditions? A) hexokinase B) pyruvate kinase C) adenylate kinase D) glucose-6-phosphatase E) phosphofructokinase-1

C

Which metabolic effect is associated with AMP-activated protein kinase (AMPK)? A) When activated, AMPK stimulates insulin release from the pancreas. B) When activated, AMPK activates fructose 2,6-bisphosphatase. C) When activated, AMPK stimulates glucose uptake in cardiac and skeletal muscle. D) When activated, AMPK both activates fructose 2,6-bisphosphatase and stimulates glucose uptake in cardiac and skeletal muscle. E) None of the answers is correct.

C

Which statement about gluconeogenesis in animal cells is TRUE? A) A rise in the cellular level of fructose-2,6-bisphosphate stimulates the rate of gluconeogenesis. B) An animal fed a large excess of fat in the diet will convert any fat not needed for energy production into glycogen to be stored for later use. C) The conversion of fructose 1,6-bisphosphate to fructose 6-phosphate is not catalyzed by phosphofructokinase-1, the enzyme involved in glycolysis. D) The conversion of glucose 6-phosphate to glucose is catalyzed by hexokinase, the same enzyme involved in glycolysis. E) The conversion of phosphoenol pyruvate to 2-phosphoglycerate occurs in two steps, including a carboxylation.

C

Which statement is NOT associated with controlling the rate of glycogen synthesis in myocytes? A) Insulin stimulates the translocation of GLUT 4 transporters to the plasma membrane. B) Insulin induces the synthesis of hexokinase I. C) Glucagon inhibits the activity of glycogen synthase via covalent modification. D) Epinephrine activates PKA, resulting in an activation of glycogen phosphorylase kinase. E) Insulin inhibits the activity of glycogen synthase kinase 3.

C

Which statement is NOT valid with respect to the enzyme adenylate kinase? A) The reversible reaction catalyzed by adenylate kinase is 2ADP n ATP + AMP. B) During a 100-meter sprint, adenylate kinase in myocytes catalyzes a biochemical reaction that provides some ATP. C) Activated adenylate kinase catalyzes the reaction that generates the second messenger cAMP from ATP. D) When cellular ATP is being used, adenylate kinase generates AMP, a signal of a low-energy state. E) Adenylate kinase is a phosphotransferase enzyme that plays a critical role in cellular energy homeostasis.

C

Which statement is TRUE for "far from equilibrium" reactions in a cell? A) They are irreversible under all conditions. B) Their standard free-energy changes are typically large and positive. C) They are common control points of regulation in a metabolic pathway. D) All of the statements are true. E) None of the statements is true.

C

Which statement is TRUE for glycogen phosphorylase b? A) It catalyzes a phosphorylytic cleavage of a(1®6) glycosidic bonds. B) It catalyzes a hydrolytic cleavage of a(1®4) glycosidic bonds. C) It is regulated both allosterically and via covalent modification. D) It uses UDP-glucose as a substrate. E) It is an important blood glucose sensor in myocytes.

C

Which statement is TRUE of glycogen synthase? A) It is activated by at least 11 different protein kinases. B) It is activated by Ca2+ ions in skeletal muscle. C) It catalyzes formation of (a1-4) glycosidic bonds. D) It uses glucose-1-phosphate as a substrate. E) All of the statements are true true.

C

During exercise, glycogen in both liver and muscle cells can be converted to glucose metabolites for ATP generation in skeletal muscle. Do liver glycogen and muscle glycogen supply the same amount of ATP to skeletal muscles? Explain

Compared to muscle cells mode glycogen is stored in liver. 10% of the liver's weight can be the stored glycogen whereas only 2% of the muscles weight can be glycogen hence we need an liver will be able to supply more glycogen than muscle. Since the glycogen weight is more in liver it will be able to supply more ATP.

Gluconeogenesis must use "bypass reactions" to circumvent three reactions in the glycolytic pathway that are highly exergonic and essentially irreversible. Reactions carried out by which three of the enzymes listed must be bypassed in the gluconeogenic pathway? 1) Hexokinase 2) Phosphoglycerate kinase 3) Phosphofructokinase-1 4) Pyruvate kinase 5) Triosephosphate isomerase A) 1, 2, 3 B) 1, 2, 4 C) 1, 4, 5 D) 1, 3, 4 E) 2, 3, 4

D

Glycogen storage disease (GSD) type 1a is associated with mutations in glucose 6-phosphatase. There are other forms of GSD type I. Which protein is likely mutated in these other forms of GSD? A) G6P transporter (T1) B) Pi transporter (T3) C) glucose transporter (GLUT2) D) T1 and T3 E) T1, T3, and GLUT2

D

Glycogenin: A) catalyzes the conversion of starch into glycogen. B) is the enzyme responsible for forming branches in glycogen. C) is the gene that encodes glycogen synthase. D) is the primer on which new glycogen chains are initiated. E) regulates the synthesis of glycogen.

D

Muscle contraction is associated with elevated levels of cytosolic calcium. Which statement describes a consequence of this increase in calcium? A) Calcium is a divalent cation, which binds to ATP and reduces electrostatic repulsion between the phosphates. Glycogen is broken down to compensate for the decreased energy available from ATP hydrolysis. B) An increased level of calcium is associated with an increase in glycogen breakdown, as calcium is an allosteric activator of glycogen phosphorylase. C) Calcium activates phosphoprotein phosphatase 1, which in turn will stimulate glycogen synthesis by dephosphorylating phosphorylase b. D) An increased level of calcium is associated with an increase in glycogen breakdown, as calcium is an allosteric activator of phosphorylase b kinase. E) All the answers are correct.

D

There is reciprocal regulation of glycolytic and gluconeogenic reactions interconverting fructose-6-phosphate and fructose-1,6-bisphosphate. Which statement about this regulation is NOT correct? A) Fructose-2,6-bisphosphate activates phosphofructokinase-1. B) Fructose-2,6-bisphosphate inhibits fructose-1,6-bisphosphatase. C) The fructose-1,6-bisphosphatase reaction is exergonic. D) The phosphofructokinase-1 reaction is endergonic. E) This regulation allows control of the direction of net metabolite flow through the pathway.

D

What is the predominant source of glucose circulating in the bloodstream of a normal individual who is asleep at 3 AM? A) catabolism of even-chained fatty acids B) gluconeogenesis in the liver C) phosphorolysis of muscle glycogen D) glycogenolysis in the liver E) dietary carbohydrates

D

Which compound is NOT associated (in some way) with glycogen granules in the cytosol of myocytes? A) glycogenin B) glucose C) inhibitor 1 D) adenylate kinase E) calmodulin

D

Which factor is an example of flux regulation, not flux control, upon an increase in blood glucose levels? A) induction of insulin B) increased glucose transport into cells C) induction of the synthesis of hexokinase D) induction of the synthesis of phosphofructokinase-1 E) activation of glycogen synthase

D

Which isozyme of lactate dehydrogenase has the LOWEST Km value for the reduction of pyruvate in skeletal muscle? A) LDH1 B) LDH2 C) LDH3 D) LDH4

D

Which pairing CORRECTLY matches an enzyme with its effector? A) phosphofructokinase-1/fructose 1,6-bisphosphate B) phosphofructokinase-2/fructose 2,6-bisphosphate C) fructose 1,6-bisphosphatase/fructose 1,6-bisphosphate D) fructose 1,6-bisphosphatase/fructose 2,6-bisphosphate E) fructose 2,6-bisphosphatase/fructose 2,6-bisphosphate

D

Which statement accurately describes the effect of insulin on the expression of the gene for glucose 6-phosphatase? A) Insulin triggers the phosphorylation of PKB, which then phosphorylates FOXO-1. Phosphorylation of FOXO-1 causes a decrease in its degradation by the proteasome, which is associated with an increase in the expression of the gene for glucose 6-phosphatase. B) Insulin activates PKB by phosphorylation, which then phosphorylates FOXO-1. Phosphorylation of FOXO-1 causes an increase in its degradation by the proteasome, which is associated with an increase in the expression of the gene for glucose 6-phosphatase. C) Insulin leads to the activation of PKA, which then phosphorylates FOXO-1. Phosphorylation of FOXO-1 causing a decrease in its degradation by the proteasome, which is associated with a decrease in the expression of the gene for glucose 6-phosphatase. D) Insulin leads to the activation of PKB, which then phosphorylates FOXO-1. Phosphorylation of FOXO-1 causing an increase in its degradation by the proteasome, which is associated with a decrease in the expression of the gene for glucose 6-phosphatase. E) Insulin activates phosphoprotein phosphatase, which then dephosphorylates FOXO-1. Dephosphorylation of FOXO-1 causes a decrease in its degradation by the proteasome and an increase in the expression of the gene for glucose 6-phosphatase.

D

Which statement is TRUE of muscle glycogen phosphorylase? A) It catalyzes phosphorolysis of the (a1 ® 6) bonds at the branch points of glycogen. B) It catalyzes the degradation of glycogen by hydrolysis of glycosidic bonds. C) It degrades glycogen to form glucose 6-phosphate. D) It exists in an active (a) form and an inactive (b) form that is allosterically regulated by AMP. E) It removes glucose residues from the reducing ends of the glycogen chains.

D

After a meal rich in carbohydrates, which change would NOT be expected in a normal human? A) increased secretion of the pancreatic hormone, insulin B) increased activity of the liver enzyme, glucokinase C) increased glucose uptake in myocytes via GLUT4 transporters D) decreased activity of GSK-3 in both myocytes and hepatocytes E) increased activity of glucose 6-phosphatase in hepatocytes

E

Although in higher animals fats are the most efficient storage form of "free-energy," not all ingested carbohydrate is converted to fat. Some is stored in the form of glycogen. Which statement does NOT apply to the metabolic benefits of storing "free-energy" in the form of glycogen? A) Glycogen can be rapidly catabolized because its structure allows for several catabolic enzymes to work in parallel. B) Glycogen in skeletal muscle can be mobilized under anaerobic conditions, whereas products of fatty acid catabolism cannot. C) In contrast to glycogen, the products of fatty acid catabolism are not gluconeogenic. D) Erythrocytes have an absolute requirement for glucose and cannot use any product of fat metabolism for their energy needs. E) Glycogen molecules are highly hydrated.

E

For an enzyme to effectively change its activity in response to a change in substrate concentration, it is MOST favorable for: A) Km to be less than cellular substrate concentrations. B) Km to be equal to cellular substrate concentrations. C) Km to be greater than cellular substrate concentrations. D) Vmax to be at the diffusion limit. E) the substrate to also be an allosteric effector.

E

Glycogen phosphorylase a can be inhibited at an allosteric site by: A) AMP. B) calcium. C) GDP. D) glucagon. E) glucose.

E

Reaction steps that are far from equilibrium are good control points in metabolic pathways because: A) the net flux through those steps is easily reversed. B) the rate differences between the forward and reverse steps are often small. C) these reactions occur most frequently in the cell. D) these reactions are highly endergonic. E) these reactions are highly exergonic.

E

The elasticity coefficient for an enzyme in a multistep pathway depends on: A) the concentration of the enzyme itself. B) the levels of regulatory molecules. C) the amounts of substrate molecules present at each step. D) both the concentration of the enzyme itself and the amounts of substrate molecules present at each step. E) both the levels of regulatory molecules and the amounts of substrate molecules present at each step.

E

The flux control coefficient for an enzyme in a multistep pathway depends on the: A) concentration of the enzyme itself. B) concentration of other enzymes in the pathway. C) levels of regulatory molecules. D) amounts of substrate molecules present at each step. E) All of the answers are correct.

E

The rate of glycolysis is tightly regulated in all cells. Regulation is important to ensure that: A) cells energy needs met. B) fuel is not wasted. C) there are appropriate levels of intermediates required for other purposes. D) fuel is not wasted and the cells energy needs are met. E) All of the answers are correct.

E

Which enzyme is NOT regulated? A) hexokinase B) pyruvate kinase C) phosphofructokinase-1 D) glyceraldehyde-3-phosphate dehydrogenase (GAPDH) E) All these enzymes are regulated.

E

Which enzyme-catalyzed reaction is LEAST sensitive to changes in the concentration of its reactants under physiological conditions? A) phosphoglycerate kinase B) GAP dehydrogenase C) adenylate kinase D) fructose 1-phosphate aldolase E) phosphofructokinase-1

E

Which factor affects the activity of glucokinase in hepatocytes? A) transcriptional regulation B) subcellular localisation C) association with a regulatory protein D) transcriptional regulation and subcellular localisation E) All of the answers are correct.

E

Which factor does NOT contribute to the regulation of enzymatic activity? A) protein phosphorylation B) allosteric regulation C) protein stability D) mRNA stability E) DNA stability

E

Which statement about mammalian glycogen synthase is NOT correct? A) It is especially predominant in liver and muscle. B) The donor molecule is a sugar nucleotide. C) The phosphorylated form of this enzyme is inactive. D) This enzyme adds glucose units to the nonreducing end of glycogen branches. E) This enzyme adds the initial glucose unit to a tyrosine residue in glycogenin.

E

Which statement does NOT describe a characteristic of phosphoprotein phosphorylase-1 (PP1)? A) PP1 can be phosphorylated by protein kinase A (PKA). B) PP1 can dephosphorylate glycogen phosphorylase, glycogen synthase, and phosphorylase kinase. C) PP1 is allosterically activated by glucose-6-phosphate. D) PP1 is inhibited by activated glycogen phosphorylase E) PP1 is phosphorylated by glycogen synthase kinase-3 (GSK3).

E

Which statement is TRUE of the glycogen branching enzyme? A) It catalyzes glycogen degradation by removing glucose from the branch points. B) It catalyzes the formation of an a 1-4 linkages during glycogen synthesis. C) It catalyzes the addition of a glucose molecule to glycogenin. D) It is allosterically regulated by fructose 2,6-bisphosphate. E) It is an enzyme that belongs to a family of transferases.

E

Which statement is TRUE regarding the regulation of pyruvate kinase? A) By activating cAMP-dependent kinase (protein kinase A), glucagon increases the activity of pyruvate kinase in the liver. B) Only in liver tissue is alanine an allosteric inhibitor of pyruvate kinase. C) Fructose 1,6-bisphosphate is a feedforward allosteric inhibitor of both pyruvate kinase L and M. D) Acetyl-CoA is an allosteric activator of pyruvate kinase M. E) ChREBP, which is activated in the presence xylulose 5-phosphate, is a transcription factor that is associated with an increase in transcription of the gene for pyruvate kinase L

E

Under what circumstances does the bifunctional protein phosphofructokinase-2/fructose 2,6-bisphosphatase (PFK-2/FBPase-2) become phosphorylated, and what are the consequences of its phosphorylation to the glycolytic and gluconeogenic pathways?

Glucagon, signaling low blood sugar, stimulates cAMP synthesis, which activates protein kinase A (PKA) to phosphorylate PFK-2/FBPase-2 (among other proteins). This phosphorylation enhances FBPase-2 activity and inhibits PFK-2 activity of the enzyme, resulting in lower levels of fructose 2,6-bisphosphate (F26BP). In the absence of F26BP as an allosteric effector, the activity of PFK-1 is reduced (inhibiting glycolysis) and the activity of FBPase-1 is enhanced (stimulating gluconeogenesis), thus enabling the liver to replenish blood glucose. See Figs. 15-16 and 15-17.

Briefly outline the pathway by which glucose activates the synthesis of pyruvate kinase.

Glucose is taken up by the cell and converted to xyulose-5-phosphate, which in turn activates protein phosphatase 2A (PP2A). PP2A dephosphorylates carbohydrate response element binding protein (ChREBP) in the cyotosol. ChREBP is then taken up into the nucleus where it is further dephosphorylated by PP2A. ChREBP then forms a complex with Mlx to up-regulate the transcription of the gene encoding pyruvate kinase.

Glycogen synthesis and glycogen breakdown are catalyzed by separate enzymes. Contrast the reactions in terms of substrate, cofactors (if any), and regulation.

Glycogen synthesis is catalyzed by glycogen synthase and employs UDP-glucose as the activated precursor:UDP-glucose + glycogen (glucose)n ⎯→ UDP + glycogen (glucose)n+1Glycogen synthase is inactivated by phosphorylation, catalyzed by cAMP-dependent protein kinase; it is activated by dephosphorylation, catalyzed by phosphoprotein phosphatase. Glycogen breakdown is catalyzed by glycogen phosphorylase, which employs pyridoxal phosphate (PLP) as a cofactor. The reaction is a phosphorolysis; the glycosidic bond is broken by the attack of Pi:Glycogen (glucose)n + Pi ⎯→ glycogen (glucose)n -1 + glucose 1-phosphate.Glycogen phosphorylase is activated by phosphorylation, catalyzed by phosphorylase kinase, and it is inactivated by dephosphorylation, catalyzed by phosphorylase a phosphatase.

Explain the role of glycogenin.

Glycogenin is a protein that acts as the "primer" for the initiation of new glycogen molecules. It catalyzes the transfer of a glucose residue from UDP-glucose to a tyrosine hydroxyl group in glycogenin, then forms a complex with glycogen synthase. As more glucose residues are added, this first glucose residue, still attached to glycogenin, becomes the reducing end of the growing glycogen chain.

What is the biological advantage of synthesizing glycogen with many branches?

Highly branched glycogen is more soluble than unbranched glycogen. In addition, both glycogen synthase and glycogen phosphorylase act at the nonreducing ends of glycogen chains. Branched glycogen has far more ends for these enzymes to work on than would the equivalent amount of linear glycogen chains. Having more ends effectively increases the concentration of substrate for the enzymes, thereby increasing the rate of glycogen synthesis and breakdown.

Describe the process of glycogen breakdown in muscle. Include a description of the structure of glycogen, the nature of the breakdown reaction and the breakdown product, and the required enzyme(s).

Muscle glycogen consists of linear polymers of (α1 → 4)-linked d-glucose, with many branches formed by (α1 → 6) glycosidic linkages to d-glucose. Glycogen phosphorylase in muscle catalyzes phosphorolytic cleavage of the terminal residue at the nonreducing ends, producing glucose 1-phosphate. When phosphorylase approaches (α1 → 6) branch points, a second enzyme (the "debranching enzyme") removes the four glucose residues nearest the branch point and reattaches them in (α1 → 4) linkage at a nonreducing end. Now phosphorylase can continue to degrade the molecule.

Explain the distinction between metabolic "regulation" and metabolic "control" in a multienzyme pathway.

Regulation refers to rebalancing the levels of metabolites along a pathway in response to a change in flux through the pathway, while control is what determines the total flux through the pathway.

Order the steps leading to glycogen synthesis resulting from the stimulation of liver cells by glucose. 1) Xyulose-5-phosphate is formed 2) Glucose is phosphorylated to glucose-6-phosphate 3) Glycogen synthase is dephosphorylated 4) Protein phosphatase 2A is activated

The correct temporal order is 2-1-4-3.

Order the steps leading to glycogen breakdown resulting from the stimulation of liver cells by glucagon. 1) Activation of protein kinase A (PKA) 2) cAMP levels rise 3) Phosphorylation of phosphorylase b 4) Phosphorylation of phosphorylase b kinase 5) Stimulation of adenyl cyclase

The correct temporal order is 5-2-1-4-3.

Briefly explain the differences between the flux control, elasticity, and response coefficients.

The flux control coefficient describes the relative contribution of each enzyme to setting the rate at which metabolites flow through a pathway (0 = no contribution; 1 = fully responsible). The elasticity coefficient expresses the responsiveness of a single enzyme to changes in the concentration of a metabolite or allosteric regulator. The response coefficient is the experimentally determined change in flux through a pathway in response to a regulatory hormone and is a function of both the flux control and elasticity coefficients.

In the glycolytic path from glucose to pyruvate, three steps are practically irreversible. What are these steps, and how is each bypassed in gluconeogenesis? What advantages does an organism gain from having separate pathways for anabolic and catabolic metabolism? What are the disadvantages?

The three irreversible steps in glycolysis are conversion of glucose to glucose 6-phosphate, catalyzed by hexokinase, conversion of fructose 6-phosphate to fructose 1,6-bisphosphate, catalyzed by phosphofructokinase-1 and conversion of PEP to pyruvate, catalyzed by pyruvate kinase (Table 15-3). The first reaction is bypassed during gluconeogenesis by the reaction catalyzed by glucose 6-phosphatase, an enzyme unique to the liver. The second is bypassed by fructose 1,6-bisphosphatase-1 (FBPase-1). The last step of glycolysis is bypassed by the two enzymes pyruvate carboxylase and PEP carboxykinase. By having separate pathways that employ different enzymes, an organism is able to control anabolic and catabolic processes separately, thus avoiding futile cycles. A potential disadvantage is the need to produce separate sets of enzymes for catabolism and anabolism.

Why is it important for proper cell function that proteins turn over rather than persisting indefinitely after being synthesized?

This is to allow changes in protein expression levels. If proteins were never degraded, it would not be possible to control the level of enzymatic activity at the level of protein synthesis since, once made, all enzymes would remain present indefinititely.

In mammalian liver, glucose-1-phosphate, the product of glycogen phosphorylase, can enter glycolysis or replenish blood glucose. Describe the reactions by which these two processes are carried out.

To enter glycolysis, glucose-1-phosphate must undergo isomerization to glucose-6-phosphate by phosphoglucomutase. To replenish glucose in the bloodstream, glucose-1-phosphate must be hydrolyzed to free glucose by glucose-1-phosphatase.

Name three glycolytic enzymes whose expression is are up-regulated in response to insulin and two gluconeogenic enzymes whose expression is down-regulated in response to insulin.

Up-regulated examples: phosphofructokinase-1, pyruvate kinase, hexokinase II and IV; down-regulated examples: PEP carboxykinase and glucose-6-phosphatase.

Explain the difference between homeostasis and equilibrium.

omeostasis is constant conditions, typically far from equilibrium - such that there is significant net reaction in the desire direction. At equilibrium, there is no net reaction; for a cell, this would be lethal.

Explain why reactions that are far from equilibrium need to be regulated.

or reactions that are far from equilibrium, the dG is very negative. What this means is that the reverse reaction cannot take place to any substantial degree even if there is some normal fluctuation in the metabolite concentrations inside the cell. So for such reactions that ratio of reactants to products inside the cell is higher than what would have been if the reaction was at equilbrium. So such reactions need to be regulated.

What are the regulatory implications for the cell with regard to ATP and AMP, given that the former are generally high, and the latter are low?

ormally, [ATP] is 5-10 mM, while [AMP] is <0.1 mM thus AMP is a much more sensitive indicator of a cell's energetic state. Small changes in ATP concentration are amplified into large changes in AMP concentration (see Table 15-1), hence many regulatory processes hinge on changes in the concentration of AMP.