Hepatic fatty acid beta-oxidation enzymes (FAO) (FAO)

Hepatic fatty acid beta-oxidation enzymes are a collective group of mitochondrial and peroxisomal proteins that catalyze the sequential breakdown of fatty acids into acetyl-CoA within the liver [4, 17]. This metabolic pathway is essential for energy production during periods of fasting or high energy demand, providing substrates for the tricarboxylic acid (TCA) cycle and facilitating the production of ketone bodies [4, 18]. Key components include the carnitine palmitoyltransferase (CPT) system for mitochondrial transport and a series of enzymes—acyl-CoA dehydrogenases, enoyl-CoA hydratases, 3-hydroxyacyl-CoA dehydrogenases, and 3-ketoacyl-CoA thiolases—that perform the four-step oxidation cycle [4, 9]. Impairment of these enzymes is a hallmark of metabolic diseases such as nonalcoholic fatty liver disease (NAFLD) and metabolic dysfunction-associated steatotic liver disease (MASLD), where reduced oxidative capacity leads to hepatic steatosis and lipotoxicity [2, 11]. Conversely, therapeutic activation of this pathway via PPARalpha agonists (e.g., fibrates) is used to treat dyslipidemia and steatosis by enhancing lipid clearance [5, 14]. Targeted inhibition of specific enzymes (e.g., CPT1 inhibition by etomoxir or 3-KAT inhibition by trimetazidine) is also explored in cardiovascular and oncology settings to shift metabolic flux [1, 15]. Safety considerations for modulating these enzymes include the risk of hypoketotic hypoglycemia and potential drug-induced liver injury or steatosis if the pathway is excessively suppressed [11, 18].

Other names

Mitochondrial fatty acid beta-oxidation enzymesHepatic FAO enzymesLiver beta-oxidation pathway enzymesFatty acid oxidation enzymes

Drugs targeting these enzymes typically act by either transcriptionally upregulating their expression via PPARalpha agonism to enhance lipid clearance, or by directly inhibiting specific enzymes like CPT1 or 3-KAT to shift metabolic substrate preference from fatty acids to glucose [1, 5, 14].