Biochemistry I Chapter 16 Problems

Match each of the following 1-4: Phosphorylase kinase → ? Protein kinase A (PKA) → ? Phosphoprotein phosphatase-1 (PP1) → ? Calmodulin (CaM) → ? 1. Enzyme that phosphorylates Ser 14 of glycogen phosphorylase b 2. Activator of phophorylase kinase 3. Enzyme that dephosphorylates and thereby deactivates both glycogen phosphorylase a and phosphorylase kinase 4. Enzyme that phosphorylates and thereby activates phosphorylase kinase

*1 *4 *3 *2

The net equation for the catabolism of six molecules of G₆P by the pentose phosphate pathway followed by conversion of ribulose-5-phosphate back to G₆P by gluconeogenesis is: G₆P + ________ [NADP+ or NADPH?] + ________ ________ → ________ [NADP+ or NADPH?] + ________ H⁺ + ________ ________ + [Pi or PPi?]

*12 *NADP+ *7 *H2O *12 *NADPH *12 *6 *CO2 *Pi

Phosphorylase kinase utilizes ________ molecules of ATP to phosphorylate glycogen phosphorylase.

*2

Match each of the following 1-4: UDP-glucose pyrophosphorylase → ? Glycogen synthase → ? Amylo-(1,4->1,6)-transglycosylase (branching enzyme) → ? Tyrosine glucosyltransferase → ? 1. Enzyme that adds glucose from UDPG to nonreducing end of glycogen. 2. Enzyme that carries out the phosphoanhydride exchange reaction between G1P and UTP. 3. Enzyme that initiates glycogen chain by transferring a glucose residue to glycogenin. 4. Enzyme that transfers a seven-residue terminal segment of glycogen to the same chain but to the C6-OH group of a glucose residue on the same chain or another chain.

*2 *1 *4 *3

Match each of the following 1-4: Uridine diphosphate glucose (UDPG) → ? Inorganic pyrophosphatase → ? Nucleoside diphosphate kinase → ? 1,5-glucolactone → ? 1. Transition-state analog that inhibits glycogen synthase. 2. High-energy intermediate in glycogen synthesis that allows it to spontaneously donate glucosyl units to the growing glycogen chai. 3. Nonspecific enzyme that hydrolyzes pyrophosphate in the formation of UDPG in glycogen synthesis. 4. Enzyme that replenishes the supply of UTP in glycogen synthesis through a phosphate-transfer from ATP.

*2 *3 *4 *1

What is the net gain/loss of ATP for one round of the Cori cycle (glucose → lactate → glucose)? ________ ATP are produced by glycolysis, and ________ ATP are consumed by gluconeogenesis, so there is a net loss of ________ ATP.

*2 *6 *4

In a cell undergoing gluconeogenesis, how many high energy intermediates are required to make one molecule of glucose if starting from oxaloacetate? 4 ATP, and 2 NADH 1 ATP, 1 GTP and 1 NADH 4 ATP and 2 GTP 2 ATP, 2 GTP and 2 NADH

*2 ATP, 2 GTP and 2 NADH **To produce one molecule of glucose you must start with TWO molecules of oxaloacetate.

Under anaerobic conditions in the muscle what is the net yield of ATP from glycolysis when glycogen is used as a starting material? 5 ATP 3 ATP 4 ATP 2 ATP

*3 ATP

What is the net energy gain when 1 molecule of glucose from glycogen stores is converted to lactate? 2 NADH + 3 ATP 2 NADH + 4 ATP 2 ATP 3 ATP 2 NADH + 2 ATP

*3 ATP

Match each of the following 1-6: Glycogen phosphorylase → ? Phosphoglucomutase → ? Pyridoxal-5'-phosphate → ? Glycogen debranching enzyme → ? Glucose-1,6-bisphosphate → ? Glucose-6-phosphatase → ? 1. A cofactor (vitamin B6 derivative) which is required for activity of glycogen phosphorylase 2. A liver enzyme that hydrolyzes glucose-6-phosphate to yield glucose and Pi. 3. A high-energy intermediate in the reaction of phosphoglucomutase. 4. An enzyme that acts as an (1->4) transglycosylase by transferring an (1->4)-linked trisaccharide unit from a limit branch of glycogen to the nonreducing end of another branch. 5. A dimeric enzyme that catalyzes the breakdown of glycogen, yielding glucose-1-phosphate (G1P) and (n-1) residues of glycogen. 6. Enzyme that converts glucose-1-phosphate (G1P) to glucose-6-phosphate (G6P).

*5 *6 *1 *4 *3 *2

Write the balanced equation for the partial catabolism of six molecules of G6P by the pentose phosphate pathway ending with Ru5P. ________ G₆P + ________ [NADP+ or NADPH?]+ ________ ________ → ________ Ru₅P + ________ [NADP+ or NADPH?] + ________ H⁺ + ________ ________

*6 *12 *NADP+ *6 *H2O *6 *12 *NADPH *12 *6 *CO2

Muscle glycogen phosphorylase is activated by AMP and inhibited by ________ and G6P.

*ATP

Is fructose-1,6-bisphosphatase activated, inhibited, or unaffected in response to a glucagon signal? Inhibited Unaffected Activated

*Activated **Glucagon signals that fuel molecules are needed in the bloodstream, and so its effects are generally to increase blood sugar and mobilize fuel stores, therefore the presence of glucagon leads to the activation of fructose-1,6-bisphosphatase a rate-limiting enzyme in gluconeogenesis.

Why is glycogen debranching enzyme necessary? It accelerates glycogen breakdown because it operates faster than glycogen phosphorylase. It allows regulation of the rate of glycogenolysis. Because glycogen phosphorylase cannot convert G1P to G6P. Because the substrate binding cleft of glycogen phosphorylase cannot accommodate chains of glycogen closer than 4-5 residues away from a branch.

*Because the substrate binding cleft of glycogen phosphorylase cannot accommodate chains of glycogen closer than 4-5 residues away from a branch.

Which of the following steps is/are not involved in the synthesis of glycogen? A. The formation of UDP-glucose from glucose-1-phosphate and UTP. B. The conversion of glucose-1-phosphate to glucose-6-phosphate. C. The synthesis of glucose-1-phosphate from glucose and ATP. Both A and B are correct. Both B and C are correct.

*Both B and C are correct. **In glycogen synthesis glucose-1-phosphate is produced from the isomerization of glucose-6-phosphate.

How does insulin promote glycogen synthesis in the liver? By inhibiting glycogen synthase. By causing the dephosphorylation of both glycogen phosphorylase and glycogen synthase. By activating glycogen phosphorylase. By binding to glycogen phosphorylase.

*By causing the dephosphorylation of both glycogen phosphorylase and glycogen synthase. **Insulin is responsible for the activation of glycogen synthase and the inhibition of glycogen phosphorylase by causing their dephosphorylation.

In humans, which one of the following statements about gluconeogenesis is TRUE? Is essential in the conversion of fatty acids to glucose Requires the enzyme hexokinase Can result in the conversion of protein into glucose Helps to reduce blood glucose after a carbohydrate-rich meal

*Can result in the conversion of protein into glucose

When secreted in the human body, the hormone glucagon causes rapid degradation of glycogen in liver cells. This mobilization of glycogen is accomplished though a signaling pathway. What is the proper temporal sequence of the following steps in this reaction cascade? A - displacement of GDP with GTP on the a-subunit of the G-proteins B - phosphorolysis of glycogen C - dissociation of the regulatory subunits activates protein kinase A D - phosphorylation of glycogen phosphorylase E - glucagons binds to a specific, transmembrane receptor F - formation of cyclic-AMP by adenylyl cyclase E-C-A-F-D-B E-A-F-C-B-D E-F-A-C-D-B E-A-F-C-D-B E-C-A-F-B-D

*E-A-F-C-D-B

Calmodulin is a Ca2+ binding protein that is involved primarily only in glycogen breakdown. False True

*False **Calmodulin is involved in numerous systems.

Which of the following is TRUE of glycogen metabolism? Glucagon acts via kinases that subsequently activate glycogen phosphorylase. The product of the glycogen phosphorylase reaction is glucose-6-phosphate. Phosphorylation activates glycogen synthase and inactivates glycogen phosphorylase. Calcium ions activate a phosphatase that subsequently activates glycogen phosphorylase. Immediately following a high carbohydrate meal, glycogen synthesis and breakdown occur simultaneously and at high rates.

*Glucagon acts via kinases that subsequently activate glycogen phosphorylase.

In humans, which one of the following statements regarding gluconeogenesis is TRUE? Gluconeogenesis is an endergonic pathway. Gluconeogenesis is activated by glucagon. Gluconeogenesis allows storage of glucose following a meal. Gluconeogenesis is activated when ADP levels are high.

*Gluconeogenesis is activated by glucagon.

In humans, which one of the following statements regarding gluconeogenesis is FALSE? Gluconeogenesis is activated when ADP levels are high. Gluconeogenesis requires the enzyme glucose-6-phosphatase. Gluconeogenesis helps to maintain blood glucose levels between meals. Gluconeogenesis is activated by glucagon.

*Gluconeogenesis is activated when ADP levels are high. **This statement is false. The conversion of pyruvate to glucose requires energy; hence this pathway is inhibited when cellular levels of ADP are high.

________ breakdown requires three enzymes, glycogen phosphorylase, glycogen debranching enzyme, and phosphoglucomutase.

*Glycogen

________ is a polymer of α (1->4)-linked D-glucose with α (1->6)) branches every 8-14 residues.

*Glycogen

Why does glycogen breakdown produce about 10% glucose, rather than glucose-6-phosphate? Glycogen debranching enzyme hydrolyzes, rather than phosphorylyzes residues that are 4-5 away from the branches. Glycogen debranching enzyme hydrolyzes, rather than phosphorylyzes the remaining branch residue, after the limit branch has been transferred. Glycogen debranching enzyme hydrolyzes, rather than phosphorylyzes the terminal branch limit residue after it has been transferred. Glycogen debranching enzyme hydrolyzes, rather than phosphorylyzes glycogen randomly at a low frequency.

*Glycogen debranching enzyme hydrolyzes, rather than phosphorylyzes the remaining branch residue, after the limit branch has been transferred.

Which one of the following enzymes is the rate-limiting enzyme in glycogen breakdown? Glycogen phosphorylase Glycogen synthase Glucose-6-phosphatase Hexokinase

*Glycogen phosphorylase

Which of the following statements regarding glycolysis and gluconeogenesis is FALSE? Glycolysis occurs in the cytosol, gluconeogenesis occurs in the cytosol and mitochondrial matrix. Glycolysis is exergonic, gluconeogenesis is endergonic. Glycolysis and gluconeogenesis share 7 reversible steps. Glycolysis is oxidative, gluconeogenesis is reductive.

*Glycolysis is exergonic, gluconeogenesis is endergonic. **This statement is false. Pathways are directional. To occur, a pathway must have an overall negative ΔG, i.e. be energetically "downhill." Because of this, a metabolic pathway is irreversible. Therefore, gluconeogenesis and glycolysis are both exergonic.

Which pair below correctly matches an enzyme with its inhibitor? Fructose-1,6-bisphosphatase / ATP Hexokinase / glucose-6-phosphate Pyruvate decarboxylase / acetyl-CoA

*Hexokinase / glucose-6-phosphate

Which of the following statements is TRUE regarding glycogen synthase? It is activated by protein kinases. It catalyzes formation of glycosidic bonds. It uses glucose-1-phosphate as a substrate. It is activated by Ca2+ ions.

*It catalyzes formation of glycosidic bonds.

Which of the following statements regarding gluconeogenesis is TRUE? It is likely to occur when cellular ATP levels are high. Fructose-2,6-bisphosphate activates gluconeogenesis. It occurs actively in skeletal muscle during periods of exercise. The conversion of phosphoenolpyruvate to 2-phosphoglycerate occurs in two steps. Gluconeogenesis is reciprocally regulated with glycogen synthesis.

*It is likely to occur when cellular ATP levels are high.

Where are the two major sites for glycogen storage in humans? Liver and muscle Muscle and kidney Adipose tissue and kidney Liver and kidney Liver and brain

*Liver and muscle

The synthesis of phosphoenolpyruvate from pyruvate proceeds through two enzyme-catalyzed reactions. These reactions: Occur in the mitochondrial matrix Lead to the net production of ATP Are allosterically regulated by fructose-1,6-bisphosphate Are both irreversible because they are coupled to nucleotide hydrolysis

*Occur in the mitochondrial matrix

Which one of the following processes most completely describes phosphorolysis reactions? Hydrolyzing a polymer and adding a phosphate group. Removing a phosphate group from a polymer. Splitting a polymer. Splitting a polymer and adding a phosphate group.

*Splitting a polymer and adding a phosphate group.

Which of the following statements regarding glycogen metabolism is FALSE? In skeletal muscle, glycogen phosphorylase is not regulated by glucagon. Starting from glycogen stores, the net yield of ATP per molecule of glucose proceeding through glycolysis is greater in skeletal muscle than in the liver. The rate-limiting reaction in glycogenolysis is a phosphorolysis reaction which generates glucose-1-phosphate. Skeletal muscle cannot export glucose because it does not contain the enzyme glucose-6-phosphatase.

*Starting from glycogen stores, the net yield of ATP per molecule of glucose proceeding through glycolysis is greater in skeletal muscle than in the liver. **Starting from glycogen stores, the net yield of ATP per molecule of glucose proceeding through glycolysis is the same in skeletal muscle and liver.

Why is an anaerobic fate of pyruvate necessary? To allow for the complete catabolism of glucose to CO2 and H2O. To allow lactate to be converted back to pyruvate which will then proceed through gluconeogenesis. To allow for the re-oxidation of NADH to NAD+, which is in limited supply. To allow for the conversion of pyruvate to acetyl-CoA.

*To allow for the re-oxidation of NADH to NAD+, which is in limited supply. **NADH must be re-oxidized to NAD+ if glycolysis is to continue. Under "normal" aerobic conditions, when oxygen is available, re-oxidation of NADH occurs via the electron transport chain. Under anaerobic conditions, however, the NAD+ is regenerated by reactions in which pyruvate is a substrate.

What is the purpose of glycogen in muscle? To activate kinases and regulate glucose metabolism. To serve as a source of fuel for ATP synthesis within that tissue. To serve primarily as a buffer of blood glucose levels. To serve as a source of glucose-6-phosphate which is subsequently dephosphorylated by glucose-6-phosphatase and transported out of the cell.

*To serve as a source of fuel for ATP synthesis within that tissue.

Glycogen synthesis and breakdown occur by separate pathways. True False

*True

Most glucose is released from glycogen in the form of glucose-1-phosphate (G1P). True False

*True

Pyridoxal-5-phosphate functions as a Schiff base (imine) in glycogen phosphorylase. False True

*True

cAMP is generated by the membrane protein adenylate cyclase, and is broken down by the enzyme phosphodieasterase. True False

*True

Pyruvate carboxylase requires the cofactor ________ for its proper function.

*biotin

Glycogen phosphorylase is regulated by allosteric interactions and by ________ modification.

*covalent

It makes metabolic sense for the same hormone signal to stimulate glycogenolysis and inhibit glycolysis in the liver while stimulating both glycogenolysis and glycolysis in muscles because the two tissues perform ________ physiological functions and therefore respond ________ to the same hormone. Liver responds by promoting glycogenolysis and gluconeogenesis to produce ________ that can be released for use by other tissues. Muscles respond to the hormone by ________ the flux of glycogen-derived ________ through glycolysis in order to generate ________ to power muscle contraction.

*different *differently *glucose *increasing *glucose *ATP

It makes metabolic sense for acetyl-CoA, which is not a substrate for gluconeogenesis, to activate pyruvate carboxylase because a high level of acetyl-CoA, the product of ________ catabolism (it is also generated from ________ and catabolism), indicates that the cell has adequate metabolic fuel available. The stimulation of pyruvate carboxylase, the first enzyme of gluconeogenesis, allows the cell to direct resources toward glucose synthesis, a mechanism for stockpiling fuel for later use.

*fatty acid *pyruvate *amino acid

An individual with a fructose-1,6-bisphosphatase deficiency would have elevated levels of pyruvate in the blood because pyruvate, a substrate for ________, cannot be converted to ________ and instead accumulates, because the gluconeogenic enzyme fructose-1,6-bisphosphatase is deficient.

*gluconeogenesis *glucose

Which of the glycolytic enzymes listed below also plays a role in gluconeogenesis? phosphofructokinase-1 glyceraldehyde-3-phosphate dehydrogenase pyruvate kinase hexokinase

*glyceraldehyde-3-phosphate dehydrogenase

Two types of regulation in glycogen metabolism are allosteric control and ________ control.

*hormonal

Subjects who consumed a meal containing a high amylose: amylopectin ratio showed a lower increase in blood glucose levels than subjects who consumed a meal with a low amylose: amylopectin ratio. Amylose is a [branched or linear or reticulated?] form of ________, so during digestion, glucose monomers can be released only ________ at a time from the ________ of the molecule. Amylopectin, a [reticulated or linear or branched?] form of ________, can release glucose from each of its ________. Consequently, the rate of glucose release from amylose is [slower or faster?] than from amylopectin, and [less or more?] glucose appears in the blood.

*linear *starch *one *end *branched *starch *branches *slower *less

Glycogen synthase transfers the glucosyl unit of UDPG to the C4-OH group on one of glycogen's ________ ends.

*non-reducing

The conversion of ________ to PEP releases CO2.

*oxaloacetate

In the Cori cycle, the lactate product of glycolysis in muscle is transformed back into glucose by the liver. List the enzymes involved in the lactate → glucose pathway. ▢ phosphoglucose isomerase ▢ glucose-6-phosphatase ▢ carbonic anhydrase ▢ phosphoglycerate kinase ▢ lactate dehydrogenase ▢ glycogen synthase ▢ GAPDH ▢ pyruvate carboxylase ▢ PEPCK ▢ dihydrofolate reductase ▢ aldolase ▢ triose phosphate isomerase ▢ amylase ▢ enolase ▢ phosphoglycerate mutase ▢ phosphofructokinase ▢ fructose-1,6-bisphosphatase

*phosphoglucose isomerase *glucose-6-phosphatase *phosphoglycerate kinase *lactate dehydrogenase *GAPDH *pyruvate carboxylase *PEPCK *aldolase *triose phosphate isomerase *enolase *phosphoglycerate mutase *fructose-1,6-bisphosphatase

Epinephrine activates cAMP-dependent protein kinase, which in turn, inactivates ________ phosphatase-1.

*phosphoprotein

The phosphorylated form of the glycogen phosphorylase is called phosphorylase a and the dephosphorylated form is called ________.

*phosphorylase b

The pathways of carbohydrate metabolism described in Chapters 15 and 16 include two reactions involving the transfer of one carbon groups. Complete the table below by naming the enzymes and the pathways where these reactions occur as well as the cofactors that are required for the transfer reactions. Chapter 15: Enzyme → ________ Pathway → ________ Cofactor → ________ Chapter 16: Enzyme → ________ Pathway → ________ Cofactor → ________

*pyruvate decarboxylase *alcoholic fermentation *thiamine pyrophosphate *pyruvate carboxylase *gluconeogenesis *biotin

Which pair below correctly matches an enzyme with its allosteric activator? phosphofructokinase-1 / fructose-1,6-bisphosphate pyruvate kinase / ADP glucose-6-phosphatase / ADP hexokinase / glucose-1-phosphate

*pyruvate kinase / ADP

Ru₅P can be converted to G₆P by the enzymes ________, and the pathway of ________: ________ Ru₅P + ________ H₂O → ________ G₆P + ________ Pi (If coefficient is equal to 1, don't keep the field empty, enter "1".)

*transaldolase, transketolase *gluconeogenesis *6 *1 *5 *1