Fatty acid oxidation pathway enzymes and transporters (FAO pathway)

The fatty acid oxidation (FAO) pathway is a fundamental metabolic process primarily occurring within the mitochondria, where fatty acids are sequentially broken down into acetyl-CoA to fuel the tricarboxylic acid (TCA) cycle and generate ATP. This complex pathway relies on a series of transporters, such as CD36 and the carnitine shuttle (CPT1, CACT, and CPT2), to move long-chain fatty acids into the mitochondrial matrix, followed by enzymatic degradation via acyl-CoA dehydrogenases and the trifunctional protein. FAO is a major energy source for high-demand tissues like the heart and skeletal muscle, especially during fasting or prolonged exercise. In clinical contexts, the pathway is targeted to treat conditions like angina and heart failure by shifting metabolism toward more oxygen-efficient glucose oxidation, and it is increasingly investigated in oncology to disrupt the metabolic flexibility of tumor cells. However, genetic deficiencies in FAO enzymes lead to severe metabolic crises, and pharmacological inhibition carries risks of systemic toxicity, including liver and muscle damage.

Other names

Beta-oxidation pathwayMitochondrial fatty acid oxidationFAOCarnitine shuttleFatty acid beta-oxidation

Inhibition of rate-limiting enzymes such as carnitine palmitoyltransferase 1 (CPT1) or 3-ketoacyl-CoA thiolase to shift energy metabolism from fatty acids to glucose; reduction of carnitine levels to limit mitochondrial fatty acid transport; or supplementation of medium-chain triglycerides to bypass transport defects.