Malonyl-CoA inhibits carnitine palmitoyltransferase-1 (CPT-1) to prevent futile cycling between fatty acid synthesis and oxidation. In the fed state, elevated malonyl-CoA inhibits CPT-1, blocking fatty acid entry into mitochondria. In which intracellular location is the carnitine shuttle system blocked by malonyl-CoA?

• A Inner mitochondrial membrane
• B Intermembrane space
• C Cytosolic face of the inner mitochondrial membrane
• D Outer mitochondrial membrane ✓

Explanation

CPT-1 (carnitine palmitoyltransferase-1) is located on the outer mitochondrial membrane and catalyzes the transfer of the acyl group from acyl-CoA to carnitine, forming acylcarnitine. This is the rate-limiting and regulated step of the carnitine shuttle. Malonyl-CoA (the first committed intermediate of fatty acid synthesis) binds allosterically to CPT-1 on the outer mitochondrial membrane, preventing acylcarnitine formation and thus blocking fatty acid entry into the mitochondrial matrix for beta-oxidation. CPT-2, which transfers the acyl group back from carnitine to CoA inside the matrix, is located on the inner mitochondrial membrane and is not regulated by malonyl-CoA. This spatial regulation elegantly prevents simultaneous synthesis and oxidation of fatty acids.

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

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

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