During vigorous anaerobic exercise, skeletal muscle lactic acid is released into circulation. In the liver, lactate is converted back to glucose via the Cori cycle. Which enzyme catalyzes the rate-limiting committed step of hepatic gluconeogenesis from oxaloacetate?

• A Pyruvate carboxylase
• B Fructose-1,6-bisphosphatase
• C Malate dehydrogenase
• D Phosphoenolpyruvate carboxykinase (PEPCK) ✓

Explanation

PEPCK catalyzes the irreversible decarboxylation and phosphorylation of oxaloacetate to phosphoenolpyruvate (PEP), which is considered the first committed step unique to gluconeogenesis. Pyruvate carboxylase converts pyruvate to oxaloacetate (a preliminary anaplerotic reaction). Fructose-1,6-bisphosphatase is a key regulatory enzyme later in the pathway, but the oxaloacetate-to-PEP step by PEPCK is the rate-limiting gate for gluconeogenesis. PEPCK is induced by glucagon and cortisol and suppressed by insulin.

Reference: Harper's Illustrated Biochemistry, 32nd ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

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