beetaoksidation

Beetaoksidation, or beta-oxidation, is the catabolic process by which fatty acids are shortened by two-carbon units to form acetyl-CoA, which then feeds energy-producing pathways such as the citric acid cycle and oxidative phosphorylation. In humans, beta-oxidation mainly occurs in mitochondria of most tissues; very long-chain and branched fatty acids are also processed in peroxisomes.

Transport and regulation are essential. Long-chain fatty acids are activated to acyl-CoA and transported into mitochondria via the carnitine shuttle, involving carnitine palmitoyltransferase I (CPT I) on the outer membrane, a translocase, and CPT II on the inner membrane. Malonyl-CoA inhibits CPT I, linking fatty acid synthesis and oxidation and helping regulate flux according to energy status.

The cycle consists of four steps. First, acyl-CoA dehydrogenase oxidizes the fatty acyl-CoA to create a trans-double bond and produces FADH2. Second, enoyl-CoA hydratase adds water across the double bond. Third, beta-hydroxyacyl-CoA dehydrogenase oxidizes the hydroxyl group and generates NADH. Fourth, beta-ketothiolase cleaves the beta-ketoacyl-CoA to release a shortened acyl-CoA and a new acetyl-CoA. Repeating the cycle shortens the fatty acid by two carbons per turn. Specific dehydrogenases handle different chain lengths: VLCAD, LCAD, MCAD, and SCAD.

Energy yield is substantial. Each cycle yields one FADH2 and one NADH, and one acetyl-CoA is produced at the end of each complete turn. An eight-carbon palmitoyl-CoA (C16) yields about 106 ATP net, accounting for the initial activation cost of two ATP.

Peroxisomal beta-oxidation handles very long-chain fatty acids and branched substrates. It begins with acyl-CoA oxidase, producing H2O2 that is broken down by catalase; the shortened products are transferred to mitochondria for further oxidation. Disorders of beta-oxidation (for example MCAD, VLCAD, CPT I/II deficiencies) can cause hypoketotic hypoglycemia, muscle weakness, and cardiomyopathy, and are topics in newborn screening and metabolic management.