A patient with type 2 diabetes mellitus is started on metformin, which activates AMP-activated protein kinase (AMPK). As a direct consequence of AMPK activation, which of the following enzymes is phosphorylated and inactivated, thereby reducing hepatic glucose output?

• A Glycogen synthase
• B Pyruvate kinase
• C Acetyl-CoA carboxylase
• D Fructose-1,6-bisphosphatase ✓

Explanation

AMPK activation suppresses hepatic gluconeogenesis partly by phosphorylating and inhibiting fructose-1,6-bisphosphatase (FBPase-1), the key regulatory enzyme of gluconeogenesis that converts fructose-1,6-bisphosphate to fructose-6-phosphate. Inhibiting FBPase-1 blocks gluconeogenic flux, reducing hepatic glucose output and lowering blood glucose levels. AMPK also inhibits acetyl-CoA carboxylase (reducing fatty acid synthesis), but the gluconeogenesis effect is most relevant to the question context.

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

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.