Carnitine acylcarnitine translocase (CACT) deficiency presents as neonatal hypoketotic hypoglycaemia with hyperammonaemia. This enzyme deficiency blocks which step in long-chain fatty acid oxidation?

• A Transfer of the acyl group from acylcarnitine on the outer to the inner face of the inner mitochondrial membrane for import into the matrix ✓
• B Activation of fatty acids to acyl-CoA by acyl-CoA synthetase in the outer mitochondrial membrane
• C Formation of acylcarnitine by CPT-1 on the outer mitochondrial membrane
• D Re-esterification of acyl-CoA from acylcarnitine in the matrix by CPT-2

Explanation

Long-chain fatty acid transport into mitochondria requires three steps: (1) CPT-1 (outer membrane) converts long-chain acyl-CoA to acylcarnitine; (2) CACT (carnitine-acylcarnitine translocase) exchanges acylcarnitine (inward) for free carnitine (outward) across the inner mitochondrial membrane; (3) CPT-2 (inner membrane matrix face) reconverts acylcarnitine to acyl-CoA in the matrix for beta-oxidation. CACT deficiency blocks translocation of acylcarnitine across the inner mitochondrial membrane (step 2), preventing long-chain fatty acids from entering the matrix. This impairs beta-oxidation and ketogenesis, causing hypoketotic hypoglycaemia, and long-chain acylcarnitines accumulate causing cardiac arrhythmias and myopathy.

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

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

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