AMPK (AMP-activated protein kinase) is the 'cellular energy sensor'. When AMP:ATP ratio rises, AMPK is activated and phosphorylates which target to simultaneously inhibit fatty acid synthesis AND activate fatty acid oxidation?

• A Pyruvate carboxylase
• B Acetyl-CoA carboxylase (ACC) ✓
• C HMG-CoA reductase and HMG-CoA synthase
• D Carnitine palmitoyltransferase-1 (CPT-1)

Explanation

AMPK phosphorylates and inactivates acetyl-CoA carboxylase (ACC), the enzyme that converts acetyl-CoA to malonyl-CoA (the committed step of fatty acid synthesis). Reduced malonyl-CoA has a dual effect: (1) directly inhibits fatty acid synthesis; (2) relieves allosteric inhibition of carnitine palmitoyltransferase-1 (CPT-1), the mitochondrial outer membrane transporter for long-chain acyl-CoA, thereby activating mitochondrial fatty acid beta-oxidation. This single phosphorylation event by AMPK thus both shuts off anabolic lipogenesis and turns on catabolic fatty acid oxidation simultaneously, making ACC the pivotal regulatory switch. AMPK also phosphorylates HMG-CoA reductase to inhibit cholesterol synthesis.

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

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.