During prolonged exercise, the AMP-to-ATP ratio increases in skeletal muscle cells, activating AMP-activated protein kinase (AMPK). AMPK phosphorylates acetyl-CoA carboxylase (ACC), and malonyl-CoA inhibits the transport of long-chain fatty acids into mitochondria. Which of the following changes is most likely to result from AMPK activation?
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Answer: D (Decreased ACC activity, decreased malonyl-CoA concentration, and increased fatty acid oxidation)
An increased AMP-to-ATP ratio signals a low cellular energy state and activates AMPK. AMPK phosphorylates and inhibits acetyl-CoA carboxylase (ACC), decreasing the production of malonyl-CoA. Because malonyl-CoA inhibits carnitine palmitoyltransferase I, the decrease in malonyl-CoA permits greater transport of long-chain fatty acids into mitochondria for beta-oxidation. Thus, ACC activity and malonyl-CoA concentration decrease while fatty acid oxidation increases. Choice A incorrectly predicts activation of ACC. Choice B is inconsistent because increased ACC activity would increase, not decrease, malonyl-CoA production. Choice C is inconsistent because decreased ACC activity would decrease, not increase, malonyl-CoA concentration.