Choose the ONE best answer.
For Questions 11.1–11.4, match the deficient enzyme to the clinical finding in selected glycogen storage diseases (GSD).
1.1. Exercise intolerance, with no rise in blood lactate during exercise
Correct answer = E. Myophosphorylase (the muscle isozyme of glycogen phosphorylase) deficiency (or, McArdle disease) prevents glycogen degradation in muscle, depriving muscle of glycogen-derived glucose, resulting in decreased glycolysis and its anaerobic product, lactate.
Correct answer = D. 4:6 Transferase (branching enzyme) deficiency (or, Andersen disease), a defect in glycogen synthesis, results in glycogen with fewer branches and decreased solubility.
Correct answer = B. Acid maltase [acid α(1→4)-glucosidase] deficiency (or, Pompe disease) prevents degradation of any glycogen brought into lysosomes. A variety of tissues are affected, with the most severe pathology resulting from heart damage.
Correct answer = A. Glucose 6-phosphatase deficiency (or, von Gierke disease) prevents the liver from releasing free glucose into the blood, causing severe fasting hypoglycemia, lactic acidemia, hyperuricemia, and hyperlipidemia.
1.2. Fatal, progressive cirrhosis and glycogen with longer-than-normal outer chains 1.3. Generalized accumulation of glycogen, severe hypotonia, and death from heart failure 1.4. Severe fasting hypoglycemia, lactic acidemia, hyperuricemia, and hyperlipidemia 1.5. Epinephrine and glucagon have which one of the following effects on hepatic glycogen metabolism?
A. Both glycogen phosphorylase and glycogen synthase are activated by phosphorylation but at significantly different rates.
B. Glycogen phosphorylase is inactivated by the resulting rise in calcium, whereas glycogen synthase is activated.
C. Glycogen phosphorylase is phosphorylated and active, whereas glycogen synthase is phosphorylated and inactive.
D. The net synthesis of glycogen is increased.
Correct answer = C. Epinephrine and glucagon both cause increased glycogen degradation and decreased synthesis in the liver through covalent modification (phosphorylation) of key enzymes of glycogen metabolism. Glycogen phosphorylase is phosphorylated and active (“a” form), whereas glycogen synthase is phosphorylated and inactive (“b” form). Glucagon does not cause a rise in calcium.
1.6. In contracting skeletal muscle, a sudden elevation of the sarcoplasmic calcium concentration will result in:
A. activation of cyclic adenosine monophosphate (cAMP)-dependent protein kinase A.
B. conversion of cAMP to AMP by phosphodiesterase.
C. direct activation of glycogen synthase b.
D. direct activation of phosphorylase kinase b.
E. inactivation of phosphorylase kinase a by the action of protein phosphatase-1.