Cardiac mitochondrial fatty acid oxidation pathway (FAO)

The cardiac mitochondrial fatty acid oxidation (FAO) pathway is the primary metabolic route for energy production in the healthy heart, supplying the majority of ATP required for contraction (Lopaschuk et al., 2010). This pathway involves the transport of long-chain fatty acids into the mitochondria via the carnitine shuttle and their subsequent degradation through the beta-oxidation cycle (Stanley et al., 2005). In pathological states such as heart failure and myocardial ischemia, the heart's reliance on FAO can become inefficient, leading to increased oxygen consumption and the accumulation of potentially toxic lipid metabolites (Fillmore et al., 2014). Therapeutic strategies targeting this pathway aim to partially inhibit FAO enzymes, such as 3-ketoacyl-CoA thiolase or carnitine palmitoyltransferase 1, to shift the heart's substrate preference toward glucose oxidation (Kantor et al., 2000). This metabolic switch improves cardiac efficiency by increasing the amount of ATP produced per molecule of oxygen consumed, thereby providing a cardioprotective effect in ischemic and failing myocardium. Drugs like trimetazidine and perhexiline have been utilized to modulate this pathway, showing benefits in reducing anginal symptoms and improving exercise tolerance. However, targeting this pathway requires careful management due to potential side effects like drug-induced parkinsonism or hepatotoxicity. Overall, the cardiac FAO pathway remains a significant area of interest for developing metabolic therapies for cardiovascular diseases.

Other names

Mitochondrial fatty acid beta-oxidationCardiac fatty acid oxidationMyocardial fatty acid metabolismBeta-oxidation pathway

Partial inhibition of mitochondrial enzymes such as 3-ketoacyl-CoA thiolase (3-KAT) or transport proteins like carnitine palmitoyltransferase 1 (CPT1) to reduce fatty acid oxidation and reciprocally increase glucose oxidation, enhancing myocardial oxygen efficiency (Kantor et al., 2000; Lopaschuk et al., 2010).