During the fed state, insulin promotes fatty acid synthesis in the liver. Which key regulatory enzyme is activated by insulin-mediated dephosphorylation to initiate this pathway?

• A Fatty acid synthase (FAS), which is directly phosphorylated by PKA and activated by insulin
• B Acetyl-CoA carboxylase (ACC), which is dephosphorylated and activated by insulin, producing malonyl-CoA ✓
• C HMGR (HMG-CoA reductase), whose activation channels acetyl-CoA into fatty acid synthesis
• D Citrate lyase, which is activated by insulin via PP2A to produce both acetyl-CoA and oxaloacetate for fatty acid synthesis

Explanation

Acetyl-CoA carboxylase (ACC) is the rate-limiting enzyme of fatty acid synthesis, converting acetyl-CoA to malonyl-CoA. Insulin activates a phosphoprotein phosphatase that dephosphorylates (and activates) ACC. Additionally, insulin increases citrate (an allosteric activator of ACC). Malonyl-CoA also inhibits carnitine acyltransferase I, preventing fatty acid oxidation simultaneously. HMGR regulates cholesterol synthesis. FAS is transcriptionally upregulated by SREBP-1c (also insulin-regulated) but is not a direct phosphorylation target for rapid activation.

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

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

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