Mitochondrial fatty acid beta-oxidation enzyme system (mFAO)

The mitochondrial fatty acid beta-oxidation (mFAO) enzyme system is a critical metabolic pathway responsible for the aerobic degradation of fatty acids into acetyl-CoA, which subsequently enters the tricarboxylic acid (TCA) cycle to generate ATP [1]. This process occurs within the mitochondrial matrix and involves a series of four recurring enzymatic steps: oxidation by acyl-CoA dehydrogenases, hydration by enoyl-CoA hydratase, oxidation by 3-hydroxyacyl-CoA dehydrogenase, and thiolysis by 3-ketoacyl-CoA thiolase [1][2]. The pathway is essential for energy homeostasis, particularly during fasting or high-energy demand in tissues like the heart and skeletal muscle [3]. Dysregulation or genetic deficiencies in these enzymes lead to fatty acid oxidation disorders (FAODs), presenting as life-threatening hypoglycemia and organ failure [4]. In the context of cardiovascular disease, pharmacological inhibition of this system is used to shift myocardial metabolism toward glucose oxidation, which requires less oxygen per mole of ATP produced, thereby providing anti-ischemic benefits [5]. Emerging research also explores the role of this pathway in supporting the metabolic demands of certain cancer cells, making it a potential target for oncology [6].

Other names

Mitochondrial fatty acid oxidationBeta-oxidation pathwaymFAO pathwayFatty acid beta-oxidation

Partial inhibition of specific enzymes within the pathway, such as carnitine palmitoyltransferase 1 (CPT1) or long-chain 3-ketoacyl-CoA thiolase (LCKAT), to shift cellular metabolism from fatty acid oxidation to glucose oxidation, thereby improving oxygen efficiency in ischemic tissues.