Fatty acid catabolism in eukaryotes — site of β-oxidation In cellular metabolism of eukaryotes, the stepwise breakdown of long-chain fatty acids by β-oxidation primarily occurs in which compartment?

Introduction / Context:
Fatty acid catabolism supplies acetyl CoA, NADH, and FADH2 to fuel ATP production. In eukaryotic cells, the canonical pathway for degrading most long chain fatty acids is β oxidation. Correctly identifying the subcellular location of this pathway is critical for understanding metabolic integration and disease states such as disorders of fatty acid oxidation.

Given Data / Assumptions:

• Question refers to eukaryotes (animals/humans).
• Process is fatty acid breakdown via β oxidation.
• Consider common long chain fatty acids after activation and transport.

Concept / Approach:

In eukaryotes, long chain acyl CoA esters are transported into mitochondria via the carnitine shuttle (CPT I, carnitine acylcarnitine translocase, CPT II). Once inside, the β oxidation spiral proceeds in the mitochondrial matrix, yielding acetyl CoA and reduced cofactors that feed the TCA cycle and the respiratory chain. Very long chain fatty acids can undergo initial shortening in peroxisomes, but the bulk energy yielding β oxidation for common chains occurs in the mitochondrial matrix.

Step-by-Step Solution:

Verification / Alternative check:

Biochemical fractionation localizes β oxidation enzymes (acyl CoA dehydrogenases, enoyl CoA hydratase, hydroxyacyl CoA dehydrogenase, thiolase) to the mitochondrial matrix. Genetic defects in CPT or matrix enzymes produce characteristic acylcarnitine profiles, confirming compartmentalization.

Why Other Options Are Wrong:

Cell membrane and ER are not the primary sites of β oxidation; ER handles lipid synthesis and desaturation. Cytosol hosts fatty acid synthesis, not mitochondrial β oxidation. Periplasmic space applies to prokaryotes, not eukaryotes.

Common Pitfalls:

Confusing peroxisomal very long chain oxidation with the main ATP generating β oxidation or mixing up synthesis (cytosol) with breakdown (mitochondria).

Final Answer:

Mitochondrial matrix