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A 24-year-old marathon runner presents with extreme thirst and production of 8 L of pale urine per day. Serum ADH levels are undetectable. Which primary mechanism best explains his polyuria?
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A 24-year-old marathon runner presents with extreme thirst and production of 8 L of pale urine per day. Serum ADH levels are undetectable. Which primary mechanism best explains his polyuria?
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A biochemistry student is studying the regulation of glucose metabolism. Which enzyme catalyzes the rate-limiting, committed step of glycolysis and is subject to allosteric regulation by AMP, ATP, and fructose-2,6-bisphosphate?
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Explanation
PFK-1 is the rate-limiting enzyme of glycolysis (step 3). It is activated by AMP, ADP, and fructose-2,6-bisphosphate, and inhibited by ATP and citrate — making it the primary flux-control point. Remember: Hexokinase (step 1) traps glucose but is not the rate-limiting step.
4 sections · Bioenergetics
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Glycolysis is a 10-step cytoplasmic pathway that converts glucose into two pyruvate molecules, yielding a net 2 ATP and 2 NADH. It operates under both aerobic and anaerobic conditions and is the gateway to cellular energy metabolism.
Three irreversible reactions act as regulatory checkpoints: Hexokinase (step 1), Phosphofructokinase-1 — PFK-1 (step 3, primary rate-limiter), and Pyruvate kinase (step 10). PFK-1 is the principal allosteric target.
Investment phase (steps 1–5): 2 ATP consumed. Payoff phase (steps 6–10): 4 ATP + 2 NADH produced. Net per glucose molecule: 2 ATP + 2 NADH + 2 pyruvate.
PFK-1 deficiency (Tarui disease) causes a glycogen storage disorder. Pyruvate kinase deficiency is the most common cause of hereditary non-spherocytic haemolytic anaemia.
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