Fatty Acid Oxidation

Step 1

Acyl-CoA synthetase activates the fatty acid in the cytoplasm by attaching CoA: fatty acid + CoA + ATP → fatty acyl-CoA + AMP + PPᵢ. This costs 2 ATP equivalents and prepares the fatty acid for entry into the mitochondria.

Step 2

Fatty acyl-CoA cannot cross the inner mitochondrial membrane directly. CPT-I transfers the acyl group to carnitine on the outer membrane, acyl-carnitine is transported across by the carnitine transporter, and CPT-II transfers the acyl group back to CoA in the matrix. This is the rate-limiting step and is inhibited by malonyl-CoA.

Step 3

Acyl-CoA dehydrogenase oxidizes fatty acyl-CoA, creating a double bond between the α and β carbons → 2,3-enoyl-CoA. The two electrons removed are transferred to FAD, producing FADH₂, which passes electrons to ubiquinone.

Step 4

Enoyl-CoA hydratase adds H₂O across the double bond of 2,3-enoyl-CoA, adding a hydroxyl group to the β-carbon → L-3-hydroxyacyl-CoA.

Step 5

3-hydroxyacyl-CoA dehydrogenase oxidizes L-3-hydroxyacyl-CoA at the β-carbon. NAD⁺ accepts the electrons → NADH + H⁺. Product is 3-ketoacyl-CoA.

Step 6

β-ketothiolase cleaves the bond between the α and β carbons via nucleophilic attack by CoA-SH, releasing acetyl-CoA. The remaining fatty acyl-CoA is 2 carbons shorter and re-enters the cycle at step 3. Cycle repeats until the fatty acid is fully degraded.