Fatty acid oxidation transport step In cellular lipid metabolism, acyl-CoA is formed in the cytosol. To undergo β-oxidation, to which location is this activated fatty acyl group transported (via the carnitine shuttle) for further oxidation?

Introduction / Context:
Understanding where fatty acids are oxidized is fundamental to biochemistry and physiology. After long-chain fatty acids are activated to acyl-CoA in the cytosol, they must be moved to the correct intracellular compartment for β-oxidation. This question tests knowledge of the carnitine shuttle and the final destination of the acyl group before it is sequentially shortened to produce acetyl-CoA, NADH, and FADH2.

Given Data / Assumptions:

• Activation to acyl-CoA occurs on the cytosolic side of the outer mitochondrial membrane.
• β-oxidation enzymes for long- and medium-chain fatty acids are located in the mitochondrial matrix.
• Transport of long-chain acyl groups across the inner membrane requires carnitine-mediated transfer.

Concept / Approach:
The carnitine shuttle converts cytosolic acyl-CoA to acyl-carnitine (via CPT-I), translocates it across the inner membrane (via CACT), and reconverts it to acyl-CoA in the matrix (via CPT-II). β-oxidation occurs in the matrix, generating FADH2 and NADH that feed the electron transport chain and acetyl-CoA that enters the citric acid cycle.

Step-by-Step Solution:
Cytosolic activation: fatty acid + CoA + ATP → acyl-CoA + AMP + PPi.Outer membrane: CPT-I forms acyl-carnitine from acyl-CoA and carnitine.Inner membrane: CACT exchanges acyl-carnitine in for free carnitine out.Matrix side: CPT-II regenerates acyl-CoA from acyl-carnitine.Matrix β-oxidation: sequential cycles yield acetyl-CoA, NADH, FADH2.

Verification / Alternative check:
In carnitine deficiency or CPT-I/CPT-II defects, long-chain fatty acid oxidation is impaired, confirming the requirement for matrix import before β-oxidation can proceed.

Why Other Options Are Wrong:
Microsomes/ER: involved in lipid synthesis and desaturation, not long-chain β-oxidation.Remains in cytosol: cytosol lacks the β-oxidation pathway for long-chain species.Peroxisomes: initiate β-oxidation of very-long-chain and branched fatty acids but do not handle all chain lengths and ultimately transfer shortened acyl groups to mitochondria.

Common Pitfalls:
Confusing activation location with oxidation location; overlooking that only the acyl group crosses as acyl-carnitine, not CoA; assuming peroxisomes handle all fatty acid oxidation.

Final Answer:
Mitochondrial matrix.