Mitochondrial fatty acid beta-oxidation pathway (mFAO) (mFAO)

Mitochondrial fatty acid beta-oxidation (mFAO) is a central metabolic pathway responsible for the sequential breakdown of fatty acids into acetyl-CoA, which subsequently enters the tricarboxylic acid (TCA) cycle to generate ATP (StatPearls, 2023). This process occurs within the mitochondrial matrix and involves a series of enzymes, including carnitine palmitoyltransferases (CPT1 and CPT2) for transport, and various acyl-CoA dehydrogenases, hydratases, and thiolases for the oxidation cycles (NCBI, 2022). mFAO is the primary energy source for the heart and skeletal muscle during periods of fasting or prolonged exercise and is essential for hepatic ketogenesis (PubMed, 2010). Dysregulation of this pathway is implicated in inherited fatty acid oxidation disorders (FAODs), where enzyme deficiencies lead to metabolic crises, as well as in common diseases like heart failure, diabetes, and certain cancers (PubMed, 2011). Therapeutic strategies targeting mFAO include the use of inhibitors like trimetazidine to shift cardiac metabolism toward glucose oxidation for better oxygen efficiency, or the use of anaplerotic agents like triheptanoin to bypass metabolic blocks in genetic disorders (PubChem, 2024).

Other names

Fatty acid beta-oxidationMitochondrial beta-oxidationFAO pathwayBeta-oxidation of fatty acids

Inhibition of 3-ketoacyl-CoA thiolase, inhibition of carnitine palmitoyltransferase 1 (CPT1), carnitine depletion, or anaplerotic substrate supplementation to modulate energy substrate utilization.