Phosphofructokinase-1 (PFK-1), the key regulatory enzyme of glycolysis, is allosterically inhibited by citrate. What is the metabolic rationale for this inhibition?

• A Citrate directly inhibits hexokinase to reduce glucose phosphorylation
• B Citrate activates gluconeogenesis by providing oxaloacetate for PEPCK
• C Citrate signals adequate TCA cycle substrate availability, preventing unnecessary glucose consumption ✓
• D Citrate is a competitive inhibitor of AMP at the allosteric site

Explanation

When the TCA cycle is running efficiently and intermediates are plentiful, citrate accumulates and is exported to the cytoplasm. High cytoplasmic citrate signals energy sufficiency. By inhibiting PFK-1 (the committed step of glycolysis), citrate prevents further catabolism of glucose when energy supply is already adequate. This is a key mechanism integrating carbohydrate and lipid metabolism: citrate is also cleaved to acetyl-CoA + OAA for fatty acid synthesis.

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

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

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