Beta-oxidation of Fatty Acid


Fatty acids are one of the major sources of energy for the human body, especially in the postabsorptive and fasted states when glucose supply is limiting. Fatty acids are stored as triglycerides in adipose tissue and are released into the bloodstream as free fatty acids when needed. Fatty acids can then enter various tissues, such as muscle, heart, liver and brain, where they undergo a catabolic process called beta-oxidation (also β-oxidation) to produce acetyl-CoA, which enters the citric acid cycle, and NADH and FADH2, which are co-enzymes used in the electron transport chain .

Beta-oxidation is named as such because the beta carbon of the fatty acid undergoes oxidation to a carbonyl group. Beta-oxidation is primarily facilitated by the mitochondrial trifunctional protein, an enzyme complex associated with the inner mitochondrial membrane, although very long chain fatty acids are oxidized in peroxisomes. Beta-oxidation consists of four sequential steps: dehydrogenation, hydration, oxidation and thiolytic cleavage. These steps are repeated until all the carbons of a fatty acid are converted to acetyl-CoA or propionyl-CoA.

Beta-oxidation is regulated by the mechanisms that control oxidative phosphorylation (i.e., by the demand for ATP). Activators such as epinephrine stimulate beta-oxidation by activating a hormone-sensitive lipase that releases fatty acids from adipose tissue. Inhibitors such as insulin inhibit beta-oxidation by dephosphorylating the lipase and preventing the release of fatty acids from adipose tissue. Moreover, malonyl-CoA, an intermediate in fatty acid synthesis, inhibits the transport of fatty acyl-CoA into mitochondria by inhibiting carnitine palmitoyltransferase I (CPT I), thus preventing a futile cycle of synthesis and degradation.

Beta-oxidation is an important metabolic pathway for generating energy from fatty acids. It also provides substrates for other pathways, such as ketogenesis in the liver and gluconeogenesis from propionyl-CoA. Defects in beta-oxidation can cause various metabolic disorders, such as fatty acid oxidation disorders (FAODs), which are characterized by hypoglycemia, hypoketosis, cardiomyopathy and muscle weakness. Therefore, understanding the biochemistry and physiology of beta-oxidation is essential for maintaining energy homeostasis and health in the human body.