Fatty acid beta-oxidation acyl-CoA-dependent enzymes (FAO enzymes)

Fatty acid beta-oxidation acyl-CoA-dependent enzymes are a group of mitochondrial proteins that catalyze the sequential breakdown of fatty acyl-CoA molecules into acetyl-CoA, which subsequently fuels the citric acid cycle for ATP production [1][2]. This metabolic process involves four recurring steps: oxidation by acyl-CoA dehydrogenases, hydration by enoyl-CoA hydratase, a second oxidation by 3-hydroxyacyl-CoA dehydrogenase, and thiolysis by 3-ketoacyl-CoA thiolase [2][3]. In clinical practice, these enzymes are significant therapeutic targets for metabolic modulation in cardiovascular diseases [4]. Drugs known as partial fatty acid oxidation (pFOX) inhibitors, such as ranolazine and trimetazidine, target the 3-ketoacyl-CoA thiolase enzyme to shift the heart's energy substrate preference from fatty acids to glucose [4][5]. This shift is advantageous during ischemia because glucose oxidation requires less oxygen per unit of ATP produced than fatty acid oxidation, thereby enhancing cardiac efficiency and reducing ischemic injury [5][6]. Beyond cardiology, genetic defects in these enzymes lead to a spectrum of metabolic disorders characterized by hypoketotic hypoglycemia and multi-organ failure, underscoring their vital role in systemic energy homeostasis [1][7].

Other names

Mitochondrial fatty acid beta-oxidation pathway enzymesAcyl-CoA-dependent beta-oxidation enzymespFOX (Partial Fatty Acid Oxidation) targetsBeta-oxidation spiral enzymes

Inhibition of specific enzymes within the mitochondrial beta-oxidation cycle, primarily 3-ketoacyl-CoA thiolase (3-KAT), to reduce the utilization of fatty acids as a fuel source and secondary stimulation of glucose oxidation, which improves myocardial oxygen efficiency.