Mitochondrial fatty acid beta-oxidation and ATP production (FAO/OXPHOS)

Mitochondrial fatty acid beta-oxidation (FAO) is a multi-step metabolic process where fatty acids are converted into acetyl-CoA, NADH, and FADH2, which are then utilized by the electron transport chain to produce ATP via oxidative phosphorylation (StatPearls, 2023). This pathway is vital for energy production, particularly in the heart and skeletal muscle, and plays a central role in systemic energy balance during fasting (Wikipedia, 2024). Dysregulation or genetic deficiency in FAO enzymes results in various metabolic disorders, including Medium-chain acyl-CoA dehydrogenase (MCAD) deficiency and other fatty acid oxidation disorders (FAODs), which can lead to hypoketotic hypoglycemia and hepatic failure (NIH GARD, 2024). In the context of cardiovascular disease, inhibiting FAO with drugs like trimetazidine can improve cardiac efficiency by shifting metabolism toward glucose oxidation, which is more oxygen-efficient (PubMed, 2022). Additionally, the pathway is a target for metabolic syndrome treatments, where PPAR agonists are used to enhance fatty acid clearance and improve insulin sensitivity (NCBI, 2023).

Other names

Fatty acid beta-oxidationMitochondrial fatty acid oxidationFAOMitochondrial energy metabolismFatty acid catabolismOxidative phosphorylation

Drugs targeting this pathway typically act by inhibiting specific enzymes like carnitine palmitoyltransferase 1 (CPT1) or 3-ketoacyl-CoA thiolase to shift metabolism from fatty acids to glucose, or by activating peroxisome proliferator-activated receptors (PPARs) to upregulate pathway components (PubMed, 2022; NCBI, 2023).