β-oxidation

β-oxidation is the principal mitochondrial pathway for catabolizing fatty acids, sequentially cleaving two-carbon acetyl-CoA units from the acyl chain through cycles of oxidation, hydration, further oxidation, and thiolysis. Each cycle of a saturated even-chain fatty acid also yields one FADH2 and one NADH, which feed the electron transport chain, making fat a highly energy-dense fuel per gram. Very-long-chain and branched-chain fatty acids require prior peroxisomal β-oxidation before mitochondrial entry. During fasting, sustained aerobic exercise, or ketogenic conditions, increased β-oxidation delivers acetyl-CoA for hepatic ketogenesis and supports muscle energy supply. Impaired β-oxidation, which occurs in fatty acid oxidation disorders and accumulates with mitochondrial dysfunction in aging, contributes to ectopic lipid deposition, insulin resistance, and metabolic inflexibility.