MCAT Biochemistry Review

Chapter 9: Carbohydrate Metabolism I: Glycolysis, Glycogen, Gluconeogenesis, and the Pentose Phosphate Pathway

Practice Questions

1.    A man collapses while running a marathon and is taken to the emergency room. His blood is found to be somewhat acidic, and further tests show increased lactate dehydrogenase activity. This enzyme is involved in which of the following pathways?

1.    Anaerobic glycolysis

2.    β-Oxidation of fatty acids

3.    Citric acid cycle

4.    Pentose phosphate pathway

2.    Which of the following organs does NOT require a constant supply of glucose from the blood for energy during a fast?

1.    Red blood cells

2.    Brain

3.    Pancreas

4.    Liver

3.    When insulin is released, it acts to increase the absorption of glucose into skeletal muscle predominantly through which of the following transporters?

1.    GLUT 1

2.    GLUT 2

3.    GLUT 3

4.    GLUT 4

4.    After an overnight fast, which of the following enzymes would be expected to have little, if any, physiological activity?

1.    Malate dehydrogenase

2.    Glucokinase

3.    α-Ketoglutarate dehydrogenase

4.    Phosphofructokinase-1

5.    The diagram below shows the effects of arsenic on the metabolism of glyceraldehyde 3-phosphate. As a result, in the presence of arsenic, how many molecules of ATP would be created directly from the conversion of two glucose molecules to four pyruvate molecules?

1.    0

2.    1

3.    2

4.    4

6.    When fatty acid β-oxidation predominates in the liver, mitochondrial pyruvate is most likely to be:

1.    carboxylated to phosphoenolpyruvate for entry into gluconeogenesis.

2.    oxidatively decarboxylated to acetyl-CoA for oxidation in the citric acid cycle.

3.    carboxylated to oxaloacetate for entry into gluconeogenesis.

4.    reduced to lactate in the process of fermentation.

7.    A biopsy is done on a child with an enlarged liver and shows accumulation of glycogen granules with single glucose residues remaining at the branch points near the periphery of the granule. The most likely genetic defect is in the gene encoding:

1.    α-1,4 phosphorylase (glycogen phosphorylase).

2.    α-1,4:α-1,6 transferase (branching enzyme).

3.    α-1,4:α-1,4 transferase (part of debranching enzyme complex).

4.    α-1,6 glucosidase (part of debranching enzyme complex).

8.    An investigator is measuring the activity of various enzymes involved in reactions of intermediary metabolism. One of the enzymes has greatly decreased activity compared to reference values. The buffer of the assay contains citrate. Which of the following enzymes will most likely be directly affected by the use of citrate?

1.    Fructose-2,6-bisphosphatase

2.    Isocitrate dehydrogenase

3.    Phosphofructokinase-1

4.    Pyruvate carboxylase

9.    After a brief period of intense exercise, the activity of muscle pyruvate dehydrogenase is greatly increased. This increased activity is most likely due to:

1.    decreased ADP.

2.    increased acetyl-CoA.

3.    increased NADH/NAD+ ratio.

4.    increased pyruvate concentration.

10.After a large, well-balanced meal, all of the following substances would be expected to be elevated EXCEPT:

1.    fatty acids.

2.    insulin.

3.    glucose.

4.    glucagon.

11.A man is given antibiotics to treat a urinary tract infection and develops an episode of red blood cell lysis. Further studies show weakness of the plasma membrane and Heinz bodies (collections of oxidized hemoglobin). Which of the following enzymes is most likely defective in this patient?

1.    Fructose-1,6-bisphosphatase

2.    Glucose-6-phosphate dehydrogenase

3.    Hexokinase

4.    Pyruvate kinase

12.The unique enzymes of gluconeogenesis are used to circumvent specific irreversible steps of glycolysis. Which of the following correctly pairs an enzyme from glycolysis with its corresponding enzyme(s) used in gluconeogenesis?

1.    Phosphofructokinase-1 / fructose-1,6-bisphosphatase

2.    Pyruvate dehydrogenase / pyruvate carboxylase and phosphoenolpyruvate carboxykinase

3.    Hexokinase / glucokinase

4.    Pyruvate kinase / glucose-6-phosphatase

13.After an overnight fast, which of the following processes would be expected to occur at an elevated rate compared with the well-fed state?

1.    Glycolysis

2.    Glycogenolysis

3.    Glycogenesis

4.    Glycerol synthesis

14.Which of the following is/are function(s) of NADPH in the cell?

1.    Antimicrobial resistance via bacterial destruction by bleach within lysosomes.

2.    Involvement in the production of the precursors to steroid hormones.

3.    Functional carriage of energy across organelle membranes for use within the mitochondria

1.    I only

2.    I and II only

3.    II and III only

4.    I, II, and III

15.Each of the following catalyzes a rate-limiting step of a carbohydrate metabolism pathway EXCEPT:

1.    hexokinase.

2.    glycogen synthase.

3.    glucose-6-phosphate dehydrogenase.

4.    fructose-1,6-bisphosphatase.

PRACTICE QUESTIONS

Answers and Explanations

1.    AUnder normal conditions, when oxygen is readily available, the pyruvate generated in glycolysis enters the mitochondrion and is converted into acetyl-CoA by the action of pyruvate dehydrogenase. During strenuous exercise, particularly by individuals in poor physical condition, the oxygen demands of the skeletal muscle may exceed the ability of the heart and lungs to provide oxygen. In this setting, the muscles switch to anaerobic glycolysis, and the pyruvate that is produced is converted to lactate by the action of lactate dehydrogenase.

2.    DThe liver, like all cells, needs a constant supply of glucose; however, it is able to produce its own glucose through gluconeogenesis (cells in the kidney can also complete low levels of gluconeogenesis). The other cells listed here are absolutely dependent on a glucose source from the blood for energy, although they may also use other fuels in addition to glucose. For example, the brain can utilize ketone bodies during lengthy periods of starvation; however, it still requires at least some glucose for proper function.

3.    DGLUT is an abbreviation for glucose transporter and describes a family of sugar transporters with varying distributions and activities. GLUT 4 is found in adipose tissue and muscle, and mediates insulin-stimulated glucose uptake; in fact, it is the only insulin-responsive glucose transporter. Insulin acts via its receptor to translocate GLUT 4 to the plasma membrane. GLUT 4 in skeletal and cardiac muscle is also stimulated by exercise through an insulin-independent pathway.

4.    BAfter an overnight fast, the liver is producing glucose and glucokinase activity would be insignificant. Glucokinase is used to trap extra glucose in liver cells as part of a storage mechanism; with low blood glucose, liver cells would be generating new glucose, not storing it. It is also in the pancreas, where it serves as a glucose sensor; if glucose levels are low, it has little activity in this tissue as well. Malate dehydrogenase, choice (A), and α-ketoglutarate dehydrogenase, choice (C), are citric acid cycle enzymes. Phosphofructokinase-1, choice (B), is a glycolytic enzyme. Other enzymes used in glycolysis, the citric acid cycle, or gluconeogenesis, such as phosphofructokinase-1, would be expected to maintain normal activity after an overnight fast, using glucose derived from glycogen or gluconeogenesis, rather than orally ingested glucose.

5.    AThe net ATP yield from glycolysis is 2 ATP per glucose. According to the question, arsenic bypasses glyceraldehyde-3-phosphate dehydrogenase and 3-phosphoglycerate kinase, directly forming 3-phosphoglycerate. 3-phosphoglycerate kinase is one of the two substrate-level phosphorylation steps and normally produces 2 ATP (one for each of the two molecules of glyceraldehyde 3-phosphate formed from glucose). If these two ATP molecules are lost, the net yield of glycolysis is now 0 ATP.

6.    CPyruvate is converted primarily into three main intermediates: acetyl-CoA (choice (B)) for the citric acid cycle (via pyruvate dehydrogenase), lactate (choice (D)) during fermentation (via lactate dehydrogenase), or oxaloacetate (choice (C)) for gluconeogenesis (via pyruvate carboxylase). High levels of acetyl-CoA, which is produced during β-oxidation, will inhibit pyruvate dehydrogenase and shift the citric acid cycle to run in the reverse direction, producing oxaloacetate for gluconeogenesis. Acetyl-CoA also stimulates pyruvate carboxylase directly.

7.    DThe pattern described for this child's glycogen demonstrates appropriate production: there are long chains of glucose monomers, implying that glycogen synthase works. There are also branch points, implying that branching enzyme, choice (B) works. During glycogenolysis, it seems that the child is able to remove individual glucose monomers and process glycogen down to the branch point itself, which requires glycogen phosphorylase, choice (A), and α-1,4:α-1,4 transferase, choice (C). The metabolic problem here is removing the final glucose at the branch point, which is an α-1,6 (not α-1,4) link. This requires choice (D)α-1,6 glucosidase.

8.    CCitrate is produced by citrate synthase from acetyl-CoA and oxaloacetate. This reaction takes place in the mitochondria. When the citric acid cycle slows down, citrate accumulates. In the cytosol, it acts as a negative allosteric regulator of phosphofructokinase-1, the enzyme that catalyzes the rate-limiting step of glycolysis.

9.    DIn most biochemical pathways, only a few enzymatic reactions are under regulatory control. These often occur either at the beginning of pathways or at pathway branch points. The pyruvate dehydrogenase (PDH) complex controls the link between glycolysis and the citric acid cycle, and decarboxylates pyruvate (the end product of glycolysis) with production of NADH and acetyl-CoA (the substrate for the citric acid cycle). After intense exercise, one would expect PDH to be highly active to generate ATP. ADP levels (choice (A)) should be high because ATP was just burned by the muscle. Acetyl-CoA (choice (B)) is an inhibitor of PDH, causing a shift of pyruvate into the gluconeogenesis pathway. A high NADH/NAD+ ratio (choice (C)) would imply that the cell is already energetically satisfied and not in need of energy, which would not be expected in intensely exercising muscle.

10.DAfter a large meal, one would expect blood to contain high levels of nutrients, such as glucose (choice (C)) and fatty acids (choice (A)), as well as regulators telling the body to utilize and store this fuel, like insulin (choice (B)). Glucagon is a peptide hormone used to raise blood sugar levels by promoting, among other processes, glycogenolysis and gluconeogenesis. Glucagon should be elevated during a fast.

11.BBased on the question stem, we can infer that the antibiotics must have been an oxidative stress on the patient (indeed, antibiotics, antimalarial medications, infections, certain foods like fava beans, and other common exposures can induce an oxidative stress). The pentose phosphate pathway is responsible for generating NADPH, which is used to reduce glutathione, one of the natural antioxidants present in the body. In individuals with glucose-6-phosphate dehydrogenase (G 6PD) deficiency, NADPH cannot be produced at sufficient levels, and oxidative stresses lead to cell membrane and protein (hemoglobin) damage. Note that you do not need to actually know the disease to answer this question; merely knowing that the enzyme must be from the pentose phosphate pathway, which is involved in mitigating oxidative stress, is sufficient.

12.A

The irreversible enzymes in glycolysis are hexokinase (or glucokinase in liver and pancreatic β-cells), phosphofructokinase-1, and pyruvate kinase. Pyruvate dehydrogenase is not considered a glycolytic enzyme because it requires the mitochondria to function. The list below shows the correct pairing of glycolytic enzymes with gluconeogenic enzymes:

·        Hexokinase or glucokinase/glucose-6-phosphatase

·        Phosphofructokinase-1/fructose-1,6-bisphosphatase

·        Pyruvate kinase/pyruvate carboxylase and phosphoenolpyruvate carboxykinase (PEPCK)

13.BAfter a fast, the liver must contribute glucose into the bloodstream through two main processes: glycogenolysis (early to intermediate fasting) and gluconeogenesis (intermediate to late fasting). The other processes would continue at normal basal levels or have decreased activity after a fast.

14.BNADPH has three primary functions: involvement in biosynthesis of lipids and cholesterol (the precursor to steroid hormones), production of bactericidal bleach in the lysosomes of certain white blood cells, and maintenance of a supply of reduced glutathione for protection against free radical damage. Energy carriage is an important function of NADH, not NADPH.

15.AHexokinase catalyzes an important irreversible step of glycolysis, but it is not the rate-limiting step. Phosphofructokinase-1 catalyzes the rate-limiting step of glycolysis. Glycogen synthase (choice (B)) catalyzes the rate-limiting step of glycogenesis, glucose-6-phosphate dehydrogenase (choice (C)) catalyzes the rate-limiting step of the pentose phosphate pathway, and fructose-1,6-bisphosphatase (choice (D)) catalyzes the rate-limiting step of gluconeogenesis.