BCH: Glycolysis Practice Questions

Glycolysis is the name given to a metabolic pathway occurring in many different cell types. It consists of 11 enzymatic steps that convert glucose to lactic acid. Glycolysis is an example of:

A) aerobic metabolism.
B) anabolic metabolism.
C) a net reductive process.
D) fermentation.
E) oxidative phosphorylation.

D) fermentation.
The anaerobic conversion of 1 mol of glucose to 2 mol of lactate by fermentation is accompanied by a net gain of:

A) 1 mol of ATP.
B) 1 mol of NADH.
C) 2 mol of ATP.
D) 2 mol of NADH.
E) none of the above.

C) 2 mol of ATP.
During strenuous exercise, the NADH formed in the glyceraldehyde 3-phosphate dehydrogenase reaction in skeletal muscle must be reoxidized to NAD+ if glycolysis is to continue. The most important reaction involved in the reoxidation of NADH is:

A) dihydroxyacetone phosphate –> glycerol 3-phosphate
B) glucose 6-phosphate –> fructose 6-phosphate
C) isocitrate –> alpha-ketoglutarate
D) oxaloacetate –> malate
E) pyruvate –> lactate

E) pyruvate –> lactate
If glucose labeled with 14C in C-1 were fed to yeast carrying out the ethanol fermentation, where would the 14C label be in the products?

A) In C-1 of ethanol and CO2
B) In C-1 of ethanol only
C) In C-2 (methyl group) of ethanol only
D) In C-2 of ethanol and CO2
E) In CO2 only

C) In C-2 (methyl group) of ethanol only
The conversion of 1 mol of fructose 1,6-bisphosphate to 2 mol of pyruvate by the glycolytic pathway results in a net formation of:

A) 1 mol of NAD+ and 2 mol of ATP.
B) 1 mol of NADH and 1 mol of ATP.
C) 2 mol of NAD+ and 4 mol of ATP.
D) 2 mol of NADH and 2 mol of ATP.
E) 2 mol of NADH and 4 mol of ATP.

E) 2 mol of NADH and 4 mol of ATP.
In an anaerobic muscle preparation, lactate formed from glucose labeled in C-3 and C-4 would be labeled in:

A) all three carbon atoms.
B) only the carbon atom carrying the OH.
C) only the carboxyl carbon atom.
D) only the methyl carbon atom.
E) the methyl and carboxyl carbon atoms.

C) only the carboxyl carbon atom.
Which of the following statements is not true concerning glycolysis in anaerobic muscle?

A) Fructose 1,6-bisphosphatase is one of the enzymes of the pathway.
B) It is an endergonic process.
C) It results in net synthesis of ATP.
D) It results in synthesis of NADH.
E) Its rate is slowed by a high [ATP]/[ADP] ratio.

B) It is an endergonic process.
When a muscle is stimulated to contract aerobically, less lactic acid is formed than when it contracts anaerobically because:

A) glycolysis does not occur to significant extent under aerobic conditions.
B) muscle is metabolically less active under aerobic than anaerobic conditions.
C) the lactic acid generated is rapidly incorporated into lipids under aerobic conditions.
D) under aerobic conditions in muscle, the major energy-yielding pathway is the pentose phosphate pathway, which does not produce lactate.
E) under aerobic conditions most of the pyruvate generated as a result of glycolysis is oxidized by the citric acid cycle rather than reduced to lactate.

E) under aerobic conditions most of the pyruvate generated as a result of glycolysis is oxidized by the citric acid cycle rather than reduced to lactate.
Glycolysis in the erythrocyte produces pyruvate that is further metabolized to:

A) CO2.
B) ethanol.
C) glucose.
D) hemoglobin.
E) lactate.

E) lactate.
When a mixture of glucose 6-phosphate and fructose 6-phosphate is incubated with the enzyme phosphohexose isomerase, the final mixture contains twice as much glucose 6-phosphate as fructose 6-phosphate. Which one of the following statements is most nearly correct, when applied to the reaction below (R = 8.315 J/mol•K and T = 298 K)?

Glucose 6-phosphate ? fructose 6-phosphate

A) G’° is +1.7 kJ/mol.
B) G’° is -1.7 kJ/mol.
C) G’° is incalculably large and negative.
D) G’° is incalculably large and positive.
E) G’° is zero.

A) G’° is +1.7 kJ/mol.
In glycolysis, fructose 1,6-bisphosphate is converted to two products with a standard free-energy change (G’°) of 23.8 kJ/mol. Under what conditions (encountered in a normal cell) will the free-energy change (G) be negative, enabling the reaction to proceed to the right?

A) If the concentrations of the two products are high relative to that of fructose 1,6-bisphosphate.
B) The reaction will not go to the right spontaneously under any conditions because the G’° is positive.
C) Under standard conditions, enough energy is released to drive the reaction to the right.
D) When there is a high concentration of fructose 1,6-bisphosphate relative to the concentration of products.
E) When there is a high concentration of products relative to the concentration of fructose 1,6-bisphosphate.

D) When there is a high concentration of fructose 1,6-bisphosphate relative to the concentration of products.
Glucose labeled with 14C in C-1 and C-6 gives rise in glycolysis to pyruvate labeled in:

A) A and C.
B) all three carbons.
C) its carbonyl carbon.
D) its carboxyl carbon.
E) its methyl carbon.

E) its methyl carbon.
If glucose labeled with 14C at C-1 (the aldehyde carbon) were metabolized in the liver, the first radioactive pyruvate formed would be labeled in:

A) all three carbons.
B) both A and C.
C) its carbonyl carbon.
D) its carboxyl carbon.
E) its methyl carbon.

E) its methyl carbon.
In an anaerobic muscle preparation, lactate formed from glucose labeled in C-2 would be labeled in:

A) all three carbon atoms.
B) only the carbon atom carrying the OH.
C) only the carboxyl carbon atom.
D) only the methyl carbon atom.
E) the methyl and carboxyl carbon atoms.

B) only the carbon atom carrying the OH.
If glucose labeled with 14C in C-3 is metabolized to lactate via fermentation, the lactate will contain 14C in:

A) all three carbon atoms.
B) only the carbon atom carrying the OH.
C) only the carboxyl carbon atom.
D) only the methyl carbon atom.
E) the methyl and carboxyl carbon atoms.

C) only the carboxyl carbon atom.
Which of these cofactors participates directly in most of the oxidation-reduction reactions in the fermentation of glucose to lactate?

A) ADP
B) ATP
C) FAD/FADH2
D) Glyceraldehyde 3-phosphate
E) NAD+/NADH

E) NAD+/NADH
In comparison with the resting state, actively contracting human muscle tissue has a:

A) higher concentration of ATP.
B) higher rate of lactate formation.
C) lower consumption of glucose.
D) lower rate of consumption of oxygen
E) lower ratio of NADH to NAD+.

B) higher rate of lactate formation.
The steps of glycolysis between glyceraldehyde 3-phosphate and 3-phosphoglycerate involve all of the following except:

A) ATP synthesis.
B) catalysis by phosphoglycerate kinase.
C) oxidation of NADH to NAD+.
D) the formation of 1,3-bisphosphoglycerate.
E) utilization of Pi.

C) oxidation of NADH to NAD+.
The first reaction in glycolysis that results in the formation of an energy-rich compound (i.e., a compound whose hydrolysis has a highly negative G’°) is catalyzed by:

A) glyceraldehyde 3-phosphate dehydrogenase.
B) hexokinase.
C) phosphofructokinase-1.
D) phosphoglycerate kinase.
E) triose phosphate isomerase.

A) glyceraldehyde 3-phosphate dehydrogenase.
Which of the following is a cofactor in the reaction catalyzed by glyceraldehyde 3-phosphate dehydrogenase?

A) ATP
B) Cu2+
C) heme
D) NAD+
E) NADP+

D) NAD+
In the phosphoglycerate mutase reaction, the side chain of which amino acid in the enzyme is transiently phosphorylated as part of the reaction?

A) serine
B) threonine
C) tyrosine
D) histidine
E) arginine

D) histidine
Inorganic fluoride inhibits enolase. In an anaerobic system that is metabolizing glucose as a substrate, which of the following compounds would you expect to increase in concentration following the addition of fluoride?

A) 2-phosphoglycerate
B) Glucose
C) Glyoxylate
D) Phosphoenolpyruvate
E) Pyruvate

A) 2-phosphoglycerate
Glycogen is converted to monosaccharide units by:

A) glucokinase.
B) glucose-6-phosphatase
C) glycogen phosphorylase.
D) glycogen synthase.
E) glycogenase.

C) glycogen phosphorylase.
Galactosemia is a genetic error of metabolism associated with:

A) deficiency of galactokinase.
B) deficiency of UDP-glucose.
C) deficiency of UDP-glucose: galactose 1-phosphate uridylyltransferase.
D) excessive ingestion of galactose.
E) inability to digest lactose.

C) deficiency of UDP-glucose: galactose 1-phosphate uridylyltransferase.
Which of the following statements is incorrect?

A) Aerobically, oxidative decarboxylation of pyruvate forms acetate that enters the citric acid cycle.
B) In anaerobic muscle, pyruvate is converted to lactate.
C) In yeast growing anaerobically, pyruvate is converted to ethanol.
D) Reduction of pyruvate to lactate regenerates a cofactor essential for glycolysis.
E) Under anaerobic conditions pyruvate does not form because glycolysis does not occur.

E) Under anaerobic conditions pyruvate does not form because glycolysis does not occur.
The ultimate electron acceptor in the fermentation of glucose to ethanol is:

A) acetaldehyde.
B) acetate.
C) ethanol.
D) NAD+.
E) pyruvate.

A) acetaldehyde.
In the alcoholic fermentation of glucose by yeast, thiamine pyrophosphate is a coenzyme required by:

A) aldolase.
B) hexokinase.
C) lactate dehydrogenase.
D) pyruvate decarboxylase.
E) transaldolase.

D) pyruvate decarboxylase.
There are a variety of fairly common human genetic diseases in which enzymes required for the breakdown of fructose, lactose, or sucrose are defective. However, there are very few cases of people having a genetic disease in which one of the enzymes of glycolysis is severely affected. Why do you suppose such mutations are seen so rarely?
The glycolytic pathway is so central to all of cellular metabolism that mutations in glycolytic enzymes are lethal; embryos with such mutations would not survive.
Define “fermentation” and explain, by describing relevant reactions, how it differs from glycolysis. Your explanation should include a discussion of the role of NADH in the reaction(s).
Fermentation is the operation of the glycolytic pathway under anaerobic conditions. Under aerobic conditions, the pyruvate produced by glycolysis is oxidized to acetyl-CoA, which passes through the citric acid cycle. NADH produced in the oxidations passes electrons to O2, and is thus recycled to NAD+ allowing the continuation of the glycolytic reactions. When no O2 is available to reoxidize the NADH produced by the glyceraldehyde 3-phosphate dehydrogenase reaction, electrons from NADH must be passed to one of the products of glycolysis, such as pyruvate or acetaldehyde, forming lactate or ethanol.
In glycolysis there are two reactions that require one ATP each and two reactions that produce one ATP each. This being the case, how can fermentation of glucose to lactate lead to the net production of two ATP molecules per glucose?
The two reactions that produce ATP in glycolysis (those catalyzed by phosphoglycerate kinase and pyruvate kinase) involve three-carbon compounds, whereas the two reactions that consume ATP occur at the level of hexoses. In glycolysis, each hexose yields two trioses, each of which undergoes the reactions that yield ATP. The ATP yield for triose reactions therefore must be doubled for stoichiometric comparison with the ATPs consumed in hexose phosphorylation. Two ATP molecules are consumed and four are produced for each glucose that passes through the pathway, resulting in a net yield of two ATP per glucose.
Briefly describe the possible metabolic fates of pyruvate produced by glycolysis in humans, and explain the circumstances that favor each.
Under aerobic conditions, pyruvate is oxidized to acetyl-CoA and passes through the citric acid cycle. Under anaerobic conditions, pyruvate is reduced to lactate to recycle NADH to NAD+, allowing the continuation of glycolysis
Show how NADH is recycled to NAD+ under aerobic conditions and under anaerobic conditions. Why is it important to recycle NADH produced during glycolysis to NAD+?
Cells contain a limited supply of NAD+ and NADH. The oxidation of glyceraldehyde 3-phosphate requires NAD+ as as electron acceptor—it converts NAD+ to NADH. Unless this NADH is recycled to NAD+, oxidative metabolism in this cell will cease for lack of an electron acceptor. Under aerobic conditions, NADH passes electrons to O2; under anaerobic conditions, NADH reduces pyruvate to lactate, and is thereby recycled to NAD+.
The yeast used in brewing the alcoholic beverage beer can break down glucose either aerobically or anaerobically using alcoholic fermentation. Explain why beer is brewed under anaerobic conditions
Since aerobic breakdown of glucose yields more energy than fermentation, in the presence of oxygen, yeast cells would not carry out fermentation and no alcohol would be produced. Under anaerobic conditions, the yeast ferment the glucose to carbon dioxide and ethanol, both of which are key ingredients in beer.
Explain with words, diagrams, or structures why lactate accumulates in the blood during bursts of very vigorous exercise (such as a 100-meter dash).
During vigorous exercise, the cardiovascular system cannot deliver O2 to the muscle tissue fast enough to maintain aerobic conditions. As glycolysis proceeds under anaerobic conditions, NAD+ is converted to NADH (during the glyceraldehyde 3-phosphate dehydrogenase reaction), but the muscle tissue has no O2 to which NADH can pass electrons. To recycle NADH to NAD+, which is essential for continuing glycolysis, electrons from NADH are used to reduce pyruvate to lactate.
Describe the fate of pyruvate, formed by glycolysis in animal skeletal muscle, under two conditions: (a) at rest, and (b) during an all-out sprint. Show enough detail in your answer to explain why pyruvate metabolism is different in these two cases.
(a) At rest, plenty of O2 is being delivered to the muscle, and pyruvate formed during glycolysis is oxidized to acetyl-CoA by the pyruvate dehydrogenase complex. Acetyl groups then enter the citric acid cycle and are oxidized to CO2 (b) Under the conditions of all-out exertion, skeletal muscle cannot be supplied with enough O2 to keep metabolism completely aerobic; under these conditions, muscle tissue must function anaerobically. Pyruvate is reduced to lactate to recycle NADH, formed by glycolysis, to NAD+, so that glycolysis can continue.
During strenuous activity, muscle tissue demands large quantities of ATP, compared with resting muscle. In white skeletal muscle (in contrast with red muscle), ATP is produced almost exclusively by fermentation of glucose to lactate. If a person had white muscle tissue devoid of the enzyme lactate dehydrogenase, how would this affect his or her metabolism at rest and during strenuous exercise?
Lactate dehydrogenase allows cells to pass electrons from NADH to pyruvate, thus regenerating NAD+ for continued glycolysis under anaerobic conditions. The lack of this enzyme would cause no significant problems at rest because aerobic red muscle tissue would function well. During strenuous exercise, however, the absence of lactate dehydrogenase would severely reduce the ability of muscle to perform anaerobically
All of the intermediated in the glycolytic pathway are phosphorylated. Give two plausible reasons why this might be advantageous to the cell.
There are at least three reasons (see p 531 for details). (a) So they will not cross the plasma membrane and be lost. (b) The resulting high-energy phosphoryl groups can be transferred directly to ADP to make ATP. (c) The high binding energy of the ionic interactions between the (-) charged phosphoryl groups and (+) charged enzyme side chains helps to stabilize the enzyme-substrate interaction.
There are two reactions in glycolysis in which an aldose is isomerized to a ketose. For one of these reactions draw the structures of the aldose and the ketose. For both reactions the G’° is positive. Briefly explain how the reactions are able to proceed without the input of additional energy.
The two reactions are those catalyzed by phosphohexose isomerase and triose phosphate isomerase:

glucose 6-phosphate –> fructose 6-phosphate
(aldose) (ketose)

dihydroxyacetone phosphate –> glyceraldehyde 3-phosphate
(ketose) (aldose)

Although both of these reactions have standard free-energy changes (G’°) that are positive, they can occur within cells because the products are immediately removed by the next step in the pathway. The result is a very low steady-state concentration of the products, making the actual free-energy changes (G) negative:

G = G’° + RT ln ([products]/[substrates])

Describe the part of the glycolytic pathway from fructose 6-phosphate to glyceraldehyde 3-phosphate. Show structures of intermediates, enzyme names, and indicate where any cofactors participate.
This part of the pathway involves the reactions catalyzed by phosphofructokinase-1, aldolase, and triose phosphate isomerase.
Describe the glycolytic pathway from fructose 1,6-bisphosphate to 1,3-bisphospho-glycerate, showing structures of intermediates and names of enzymes. Indicate where any cofactors participate.
The answer should show the reactions catalyzed by aldolase, triose phosphate isomerase, and glyceraldehyde 3-phosphate dehydrogenase.
Yeast can metabolize D-mannose to ethanol and CO2. In addition to the glycolytic enzymes, the only other enzyme needed is phosphomannose isomerase, which converts mannose 6-phosphate to fructose 6-phosphate. If mannose is converted to ethanol and CO2 by the most direct pathway, which of the compounds and cofactors in this list are involved?

A. Lactate
B. Acetaldehyde
C. Acetyl-CoA
D. FAD
E. Glucose 6-phosphate
F. Fructose 1-phosphate
G. Pyruvate
H. Lipoic acid
I. Thiamine pyrophosphate
J. Dihydroxyacetone phosphate

B.) Acetaldehyde
G.) Pyruvate
I.) Thiamine pyrophosphate
J.) Dihydroxyacetone phosphate
In the conversion of glucose to pyruvate via glycolysis, all of the following enzymes participate. Indicate the order in which they function by numbering them.
___ hexokinase
___ triose phosphate isomerase
___ phosphohexose isomerase
___ enolase
___ glyceraldehyde 3-phosphate dehydrogenase
___ pyruvate kinase
___ phosphofructokinase-1
1,4,2,6,5,7,3
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