# Biochemistry - Chapter 9 - Carbohydrate Metabolism I (Practice Questions)

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 shows increased lactate dehydrogenase activity. This enzyme is involved in which of the following pathways?

A. Anaerobic glycolysis
B. Beta-Oxidation of fatty acids
C. Citric acid cycle
D. Pentose phosphate pathway
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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 shows increased lactate dehydrogenase activity. This enzyme is involved in which of the following pathways?

A. Anaerobic glycolysis
B. Beta-Oxidation of fatty acids
C. Citric acid cycle
D. Pentose phosphate pathway
A. Under 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 fermented to lactate by the action of lactate dehydrogenase.
D. The 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.
D. GLUT 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 muscle is also stimulated by exercise through an insulin-independent pathway.
B. After 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, (A), and alpha-ketoglutarate dehydrogenase, (C), are citric acid cycle enzymes. Phosphofructokinase-1, (D), 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.
When fatty acid beta-oxidation predominates in the liver, mitochondrial pyruvate is most likely to be:

A. carboxylated to phosphoenolpyruvate for entry into gluconeogenesis.
B. oxidatively decarboxylated to acetyl-CoA for oxidation in the citric acid cycle.
C. carboxylated to oxaloacetate for entry into gluconeogenesis.
D. reduced to lactate in the process of fermentation.
C. Pyruvate is converted primarily into three main intermediates: acetyl-CoA, (B), for the citric acid cycle (via pyruvate dehydrogenase complex); lactate, (D), during fermentation (via lactate dehydrogenase); or oxaloacetate, (C), for gluconeogenesis (via pyruvate carboxylase). High levels of acetyl-CoA, which is produced during beta-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.
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:

A. alpha-1,4 phosphorylase (glycogen phosphorylase).
B. alpha-1,4:alpha-1,6 transferase (branching enzyme).
C. alpha-1,4:alpha-1,4 transferase (part of deb ranching enzyme complex).
D. alpha-1,6 glucosidase (part of debranching enzyme complex).
D. The 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, (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, (A), and alpha-1,4:alpha-1,4 transferase, (C). The metabolic problem here is removing the final glucose at the branch point, which is an alpha-1,6 (not alpha-1,4) link. This requires (D), alpha-1,6 glucosidase.
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?

A. Fructose-2,6-bisphosphatase
B. Isocitrate dehydrogenase
C. Phosphofructokinase-1
D. Pyruvate carboxylase
C. Citrate 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.
D. In 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, (A), should be high because ATP was just burned by the muscle. Acetyl-CoA, (B), is an inhibitor of PDH, causing a shift of pyruvate into the gluconeogenic pathway. A high NADH/NAD+ ratio, (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.
D. After a large meal, one would expect blood to contain high levels of nutrients, such as glucose, (C), and fatty acids, (A), as well as regulators telling the body to utilize and store this fuel, like insulin, (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.
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?

A. Fructose-1,6-bisphosphatase
B. Glucose-6-phosphate dehydrogenase
C. Hexokinase
D. Pyruvate kinase
B. Based 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 (G6PD) 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.