During hepatic gluconeogenesis, the irreversible pyruvate kinase step of glycolysis is bypassed by two separate enzymes acting sequentially. In which subcellular compartment does the first of these reactions occur, and what cofactor does it require?

• A Cytosol, requiring thiamine pyrophosphate
• B Mitochondrial matrix, requiring biotin ✓
• C Endoplasmic reticulum lumen, requiring manganese
• D Cytosol, requiring NADPH

Explanation

Pyruvate carboxylase, located in the mitochondrial matrix, converts pyruvate to oxaloacetate using ATP and the biotin prosthetic group for CO2 transfer, and it is allosterically activated by acetyl-CoA. Oxaloacetate then leaves as malate or aspartate, and PEP carboxykinase completes the bypass in the cytosol. Thiamine pyrophosphate serves pyruvate dehydrogenase and transketolase, not this reaction.

Reference: Lippincott's Illustrated Reviews: Biochemistry, 8th ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

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