Myocardial fatty acid metabolism machinery

The myocardial fatty acid metabolism machinery refers to the integrated system of transporters and enzymes responsible for the uptake and mitochondrial oxidation of long-chain fatty acids in the heart. Under normal physiological conditions, fatty acid oxidation (FAO) provides approximately 60-90% of the heart's ATP requirements, with the remainder coming from glucose and lactate [Lopaschuk et al., 2010]. Key components of this machinery include the CD36 translocase (Fatty Acid Translocase), carnitine palmitoyltransferase 1 (CPT1) for mitochondrial entry, and the enzymes of the beta-oxidation spiral such as 3-ketoacyl-CoA thiolase (3-KAT) [Stanley et al., 2005]. In pathological states like ischemia or heart failure, the heart's reliance on fatty acids can become maladaptive because FAO requires more oxygen per mole of ATP produced compared to glucose oxidation, and the accumulation of lipid intermediates can lead to lipotoxicity [Fillmore et al., 2014]. Pharmacological agents like trimetazidine and ranolazine target this machinery by partially inhibiting FAO, thereby forcing a metabolic shift toward glucose oxidation. This shift improves myocardial efficiency, reduces oxygen demand, and provides cardioprotection in patients with chronic stable angina and heart failure [Fragasso et al., 2006].

Other names

Cardiac fatty acid oxidation pathwayMyocardial lipid metabolic machineryFatty acid transport and oxidation systemCardiac FAO machinery

Inhibition of long-chain 3-ketoacyl-CoA thiolase (3-KAT) or carnitine palmitoyltransferase 1 (CPT1) to shift myocardial energy substrate preference from fatty acids to glucose oxidation, which is more oxygen-efficient [Lopaschuk et al., 2010; Stanley et al., 2005].