NBME-Style Case-Based Questions on the regulation of glycolysis with explanations

Question 1: A 25-year-old man runs a marathon. After 20 miles, his muscle cells are relying heavily on glycolysis for energy production. Which of the following changes is most likely increasing the rate of glycolysis in his muscles?

A. Accumulation of alanine
B. Decreased availability of glucose
C. Decreased oxygen levels
D. Increased AMP concentration
E. Increased citrate concentration

Question 2: A 40-year-old man consumes a carbohydrate-rich meal, leading to high insulin levels. Which of the following mechanisms explains how glycolysis is activated after this meal?

A. Activation of pyruvate dehydrogenase by phosphorylation
B. Conversion of pyruvate to alanine
C. Increase in fructose-2,6-bisphosphate concentration
D. Inhibition of hexokinase by glucose-6-phosphate
E. Phosphorylation of phosphofructokinase-1

Question 3: A 60-year-old man with poorly controlled type 1 diabetes is in a fasting state. Which of the following changes in enzyme activity is expected in his liver?

A. Decreased activity of pyruvate kinase
B. Increased activity of hexokinase
C. Increased concentration of fructose-2,6-bisphosphate
D. Increased dephosphorylation of phosphofructokinase-1
E. Increased glycolytic activity

Question 4: A 55-year-old man with chronic obstructive pulmonary disease (COPD) experiences hypoxia. Which of the following changes is most likely to occur in his tissues under these conditions?

A. Activation of pyruvate dehydrogenase
B. Decreased expression of glycolytic enzymes
C. Increased ATP production via oxidative phosphorylation
D. Increased expression of hypoxia-inducible factor-1 (HIF-1)
E. Inhibition of PFK-1 by AMP

Question 5: A 35-year-old woman consumes a carbohydrate-rich meal, resulting in increased insulin secretion. Which of the following changes in enzyme activity is expected in her liver?

A. Activation of pyruvate kinase by phosphorylation
B. Conversion of fructose-2,6-bisphosphate to fructose-6-phosphate
C. Dephosphorylation and activation of pyruvate kinase
D. Inhibition of hexokinase by ATP
E. Phosphorylation of phosphofructokinase-1 by glucagon

 Explanations

1. Answer: D. Increased AMP concentration: During prolonged exercise, ATP levels drop, leading to an accumulation of AMP, which signals low energy. AMP allosterically activates PFK-1, enhancing glycolysis to produce more ATP for energy.

  • A. Accumulation of alanine: Alanine inhibits pyruvate kinase, slowing down glycolysis. This is part of a feedback mechanism signaling that enough pyruvate has been produced.
  • B. Decreased availability of glucose: This would reduce glycolysis, not increase it.
  • C. Decreased oxygen levels: While decreased oxygen forces reliance on glycolysis, it doesn’t directly activate it. AMP is the immediate signal for low energy.
  • E. Increased citrate concentration: Citrate inhibits PFK-1, signaling high energy status and slowing glycolysis.

2. Answer: C. Increase in fructose-2,6-bisphosphate concentration: Fructose-2,6-bisphosphate (F2,6BP) allosterically activates PFK-1, enhancing glycolysis. Insulin increases the production of F2,6BP via activation of PFK-2, ensuring that glycolysis proceeds efficiently after a meal.

  • A. Activation of pyruvate dehydrogenase by phosphorylation: Pyruvate dehydrogenase (PDH) converts pyruvate to acetyl-CoA for the TCA cycle, not glycolysis. Also, PDH is inhibited, not activated, by phosphorylation.
  • B. Conversion of pyruvate to alanine: This would reduce glycolytic flux by diverting pyruvate from energy production.
  • D. Inhibition of hexokinase by glucose-6-phosphate: This occurs in cases of excess glucose-6-phosphate, slowing glycolysis, not enhancing it.
  • E. Phosphorylation of phosphofructokinase-1: PFK-1 is regulated allosterically, not by phosphorylation.

3. Answer: A. Decreased activity of pyruvate kinase : During fasting or diabetes, glucagon leads to the phosphorylation and inhibition of pyruvate kinase, reducing glycolysis in the liver to conserve glucose for essential tissues.

  • B. Increased activity of hexokinase: Hexokinase is not significantly regulated by glucagon or fasting. In the liver, glucokinase (not hexokinase) plays a role, and its activity decreases during fasting.
  • C. Increased concentration of fructose-2,6-bisphosphate: Glucagon decreases F2,6BP levels to inhibit glycolysis.
  • D. Increased dephosphorylation of phosphofructokinase-1: PFK-1 is not regulated by phosphorylation; it is regulated allosterically by AMP, ATP, and F2,6BP.
  • E. Increased glycolytic activity: Glycolysis decreases during fasting due to reduced enzyme activity and hormonal regulation.

4. Answer: D. Increased expression of hypoxia-inducible factor-1 (HIF-1): In hypoxic conditions, HIF-1 increases the expression of glycolytic enzymes to enhance glycolysis and compensate for the reduced ATP production from oxidative phosphorylation.

  • A. Activation of pyruvate dehydrogenase: Pyruvate dehydrogenase is inhibited during hypoxia to prevent excessive acetyl-CoA formation when oxygen is limited.
  • B. Decreased expression of glycolytic enzymes: Glycolytic enzyme expression increases in response to hypoxia.
  • C. Increased ATP production via oxidative phosphorylation: ATP production via oxidative phosphorylation decreases under hypoxia.
  • E. Inhibition of PFK-1 by AMP: AMP activates, rather than inhibits, PFK-1 to stimulate glycolysis during energy deficiency.

5. Answer: C. Dephosphorylation and activation of pyruvate kinase: After a carbohydrate-rich meal, insulin promotes the dephosphorylation of pyruvate kinase, activating it to enhance glycolysis and facilitate glucose utilization in the liver.

  • A. Activation of pyruvate kinase by phosphorylation: Phosphorylation inhibits, rather than activates, pyruvate kinase.
  • B. Conversion of fructose-2,6-bisphosphate to fructose-6-phosphate: This conversion occurs during fasting when glucagon is high, not in the fed state.
  • D. Inhibition of hexokinase by ATP: ATP inhibits PFK-1, not hexokinase, under conditions of energy sufficiency.
  • E. Phosphorylation of phosphofructokinase-1 by glucagon: PFK-1 is regulated allosterically, not by phosphorylation.
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