Betaoksidatioon

Beta-oksidatioon, commonly referred to as beta-oxidation, is the catabolic process by which fatty acids are broken down to acetyl-CoA units, generating NADH and FADH2 for ATP production. In most tissues this pathway occurs in mitochondria, while peroxisomes handle very long-chain and branched fatty acids and deliver shorter products to mitochondria for further oxidation.

The process proceeds through repeating cycles that shorten the fatty acyl chain by two carbons each time, releasing one molecule of acetyl-CoA. Each cycle involves four steps: dehydrogenation of the fatty acyl-CoA by acyl-CoA dehydrogenase (producing FADH2), hydration by enoyl-CoA hydratase, oxidation by hydroxyacyl-CoA dehydrogenase (producing NADH), and thiolysis by thiolase to yield acetyl-CoA and a shortened acyl-CoA. This cycle continues until only acetyl-CoA remains. For unsaturated fatty acids, additional enzymes such as enoyl-CoA isomerase and, for polyunsaturated substrates, 2,4-dienoyl-CoA reductase, rearrange double bonds to allow continued oxidation.

Acetyl-CoA enters the citric acid cycle, while NADH and FADH2 feed electrons into the electron transport chain for ATP generation. In the liver during fasting, acetyl-CoA can also be channeled into ketone body synthesis. Regulation is linked to cellular energy status and substrate availability. The carnitine shuttle, including CPT1, governs entry of long-chain fatty acids into mitochondria and is inhibited by malonyl-CoA, preventing concurrent fatty acid synthesis and oxidation.

Defects in beta-oxidation enzymes cause metabolic disorders such as MCAD and VLCAD deficiencies, with symptoms like hypoglycemia and metabolic crises. Diagnosis often uses acylcarnitine profiling.