Fatty acid synthesis requires cytosolic acetyl-CoA, but acetyl-CoA produced by pyruvate dehydrogenase in mitochondria cannot cross the inner mitochondrial membrane. In the well-fed state, acetyl-CoA reaches the cytosol primarily in the form of:

• A Acetylcarnitine, cleaved by carnitine acetyltransferase
• B Citrate, cleaved by ATP-citrate lyase ✓
• C Acetyl phosphate, cleaved by phosphotransacetylase
• D Acetoacetate, cleaved by thiophorase

Explanation

High mitochondrial citrate from active pyruvate dehydrogenase and the TCA cycle spills into the cytosol via the tricarboxylate carrier. Cytosolic ATP-citrate lyase splits it back into acetyl-CoA and oxaloacetate using ATP, providing substrate for acetyl-CoA carboxylase. This citrate shuttle also supplies the NADPH needed for reductive synthesis, since exported oxaloacetate becomes malate then pyruvate via malic enzyme, generating NADPH. Acetylcarnitine participates in the acetyl unit traffic of some tissues but is not the main lipogenic route.

Reference: Lehninger Principles of Biochemistry, 8th ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

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