Peroxisomal and mitochondrial fatty acid beta-oxidation pathway (FAO pathway)

The peroxisomal and mitochondrial beta-oxidation pathways are essential metabolic sequences responsible for the catabolism of fatty acids into acetyl-CoA, which subsequently enters the citric acid cycle for ATP production (StatPearls, 2023). Mitochondrial beta-oxidation primarily handles short-, medium-, and long-chain fatty acids, whereas peroxisomal beta-oxidation is specialized for the oxidation of very-long-chain fatty acids (VLCFA) and branched-chain fatty acids that the mitochondria cannot process directly (NCBI Bookshelf, 2022). These pathways play a pivotal role in systemic energy balance, particularly during periods of fasting or intense physical exertion. Dysregulation of these processes is central to the pathogenesis of various conditions, including inherited fatty acid oxidation disorders (FAODs), X-linked adrenoleukodystrophy, and metabolic syndrome components like non-alcoholic fatty liver disease (NAFLD) (GeneReviews, 2020). Pharmacological intervention involves either the activation of these pathways, such as via PPAR agonists to treat dyslipidemia, or their inhibition using CPT1 inhibitors or 3-KAT inhibitors to treat angina or certain cancers (PubChem). Consequently, these pathways represent a complex but vital therapeutic target system in metabolic, cardiovascular, and oncological medicine.

Other names

Fatty acid beta-oxidationFAOMitochondrial beta-oxidationPeroxisomal beta-oxidationFatty acid degradation

Modulation of fatty acid transport via CPT1 inhibition, inhibition of 3-ketoacyl-CoA thiolase (3-KAT), or transcriptional upregulation of pathway enzymes via PPAR activation.