AMP-activated protein kinase (AMPK) is activated by a high AMP:ATP ratio. In skeletal muscle during vigorous exercise, AMPK activation leads to which combination of effects?

• A Activation of acetyl-CoA carboxylase (ACC) and inhibition of malonyl-CoA decarboxylase, increasing fatty acid synthesis
• B Phosphorylation of ACC inactivating it (reducing malonyl-CoA), and stimulation of GLUT4 translocation to the plasma membrane ✓
• C Activation of HMG-CoA reductase and acetyl-CoA carboxylase to replenish energy substrates
• D Inhibition of GLUT4 translocation and activation of glycogen synthase to rebuild glycogen stores

Explanation

AMPK phosphorylates and inactivates acetyl-CoA carboxylase (ACC), reducing malonyl-CoA levels. Since malonyl-CoA is an allosteric inhibitor of carnitine palmitoyltransferase I (CPT-I), its reduction allows fatty acyl-CoA entry into mitochondria for beta-oxidation, increasing fat fuel use. Simultaneously, AMPK promotes GLUT4 vesicle translocation to the sarcolemma via a PI3K-independent mechanism, increasing glucose uptake. AMPK also inhibits HMG-CoA reductase (energy-consuming cholesterol synthesis) and glycogen synthase, prioritizing catabolism over anabolism.

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

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