Hepatic fatty acid synthesis requires NADPH at two steps catalyzed by the fatty acid synthase complex and one step catalyzed by acetyl-CoA carboxylase. Besides the pentose phosphate pathway, which hepatic enzyme is a major direct source of this NADPH?

• A Glucose-6-phosphatase
• B Pyruvate carboxylase
• C Malic enzyme (NADP-dependent malate dehydrogenase) ✓
• D NAD-dependent malate dehydrogenase

Explanation

Oxaloacetate produced by ATP citrate lyase is reduced to malate, then cytosolic malic enzyme oxidatively decarboxylates malate to pyruvate while generating NADPH. This supplies a substantial fraction of the reducing equivalents for fatty acid synthesis alongside glucose-6-phosphate dehydrogenase of the pentose phosphate pathway. The NAD-dependent cytosolic malate dehydrogenase produces NADH, not NADPH, which eliminates option D.

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

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

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