Myocardial fatty acid uptake and beta-oxidation pathway (MFAO) (MFAO)

The myocardial fatty acid uptake and beta-oxidation pathway is the primary metabolic route for energy production in the adult heart, supplying 60-90% of the ATP required for cardiac contraction (Stanley et al., 2005, PMID: 15951474). This complex process involves the uptake of long-chain fatty acids via transporters such as CD36, their activation to acyl-CoA, and their subsequent transport into the mitochondria through the carnitine palmitoyltransferase (CPT) system (Fillmore et al., 2014, PMID: 24939237). Once inside the mitochondrial matrix, fatty acids undergo a four-step spiral of beta-oxidation to generate acetyl-CoA for the tricarboxylic acid cycle. In conditions such as chronic heart failure and myocardial ischemia, the heart's over-reliance on fatty acids can become maladaptive, leading to reduced cardiac efficiency and the accumulation of toxic lipid intermediates (Lopaschuk et al., 2021, PMID: 33531697). Pharmacological agents like trimetazidine and ranolazine target this pathway by inhibiting specific enzymes or transporters to promote a metabolic shift toward glucose oxidation. This shift improves the heart's oxygen efficiency, as glucose oxidation requires less oxygen per mole of ATP produced, providing therapeutic benefits in treating angina and heart failure.

Other names

Cardiac fatty acid oxidationMyocardial fatty acid metabolismFAO pathwaypFOX inhibitionCardiac lipid oxidation

Partial inhibition of fatty acid oxidation (pFOX inhibition) to stimulate glucose oxidation and improve myocardial oxygen efficiency via the Randle cycle (Lopaschuk et al., 2010, PMID: 20847317).