Mitochondrial long-chain 3-ketoacyl-CoA thiolase (LC-KAT)

Mitochondrial long-chain 3-ketoacyl-CoA thiolase is a key enzyme in the mitochondrial beta-oxidation pathway, specifically responsible for the final step in the breakdown of long-chain fatty acids. It functions as the beta subunit of the mitochondrial trifunctional protein (MTP) complex, which is essential for energy production in high-demand tissues such as the heart and skeletal muscle (UniProt P55084). By catalyzing the thiolytic cleavage of 3-ketoacyl-CoA, it generates acetyl-CoA for the citric acid cycle. In clinical medicine, this enzyme is a therapeutic target for metabolic modulation in cardiovascular diseases like chronic stable angina. Drugs such as trimetazidine inhibit this enzyme to shift the heart's energy source from fatty acids to glucose, which requires less oxygen per unit of ATP produced, thereby protecting the myocardium during ischemia (PubChem CID 5574). Genetic mutations in the HADHB gene, which encodes this thiolase, result in mitochondrial trifunctional protein deficiency, a condition that can cause life-threatening metabolic crises, cardiomyopathy, and neuropathy (NIH GARD).

Other names

3-ketoacyl-CoA thiolaseHydroxyacyl-CoA dehydrogenase trifunctional effector subunit betaHADHBBeta-ketothiolaseTP-betaTrifunctional enzyme subunit beta, mitochondrial

Inhibition of long-chain 3-ketoacyl-CoA thiolase to shift myocardial metabolism from fatty acid oxidation to glucose oxidation, improving oxygen efficiency.