betaoksidasyona

Betaoksidasyona, often referred to as beta-oxidation, is a metabolic pathway that degrades fatty acids into acetyl-CoA units. It provides reducing equivalents in the form of NADH and FADH2 that feed the mitochondria’s energy-producing processes. In most tissues the initial steps occur in mitochondria; very long-chain fatty acids are partially shortened in peroxisomes before mitochondrial oxidation can proceed.

Activation and transport: fatty acids are activated in the cytosol to acyl-CoA by acyl-CoA synthetases. Because acyl-CoA cannot cross the inner mitochondrial membrane, the carnitine shuttle transports them as acylcarnitines. Carnitine palmitoyltransferase I (CPT I) converts acyl-CoA to acylcarnitine on the outer membrane, the translocase transfers it across, and CPT II regenerates acyl-CoA inside the matrix.

Beta-oxidation cycles themselves: within the matrix, each cycle shortens the fatty acyl chain by two carbons. An initial dehydrogenation by acyl-CoA dehydrogenase forms an enoyl-CoA with FADH2; hydration by enoyl-CoA hydratase yields hydroxyacyl-CoA; a second dehydrogenation by hydroxyacyl-CoA dehydrogenase produces a ketoacyl-CoA and NADH; thiolysis by beta-ketothiolase cleaves off acetyl-CoA and leaves a shortened acyl-CoA. The cycle repeats until only acetyl-CoA units remain. Unsaturated fats require isomerase or reductase steps to accommodate double bonds.

Energy yield and regulation: each cycle yields NADH and FADH2 and releases acetyl-CoA for the TCA cycle. Total ATP depends on chain length; palmitate is commonly cited as about 106 ATP after transport costs. Malonyl-CoA inhibits CPT I to regulate oxidation.

Clinical relevance: defects in CPT I/II or acyl-CoA dehydrogenases (for example MCAD deficiency) cause hypoketotic hypoglycemia and metabolic crises during fasting. Peroxisomal beta-oxidation handles very long-chain fatty acids; defects contribute to broader metabolic disorders.