Hydroxyacyl-CoA dehydrogenase trifunctional protein subunit beta (HADHB)

Hydroxyacyl-CoA dehydrogenase trifunctional protein subunit beta (HADHB) is a mitochondrial enzyme that constitutes the beta subunit of the mitochondrial trifunctional protein (MTP) complex [1] UniProt P55084. It is specifically responsible for the 3-ketoacyl-CoA thiolase activity, which catalyzes the final step of the beta-oxidation spiral for long-chain fatty acids, converting 3-ketoacyl-CoA into acyl-CoA and acetyl-CoA [4] NCBI Gene 3032. This process is vital for energy production, particularly in high-demand tissues such as the heart and skeletal muscle. Genetic mutations in the HADHB gene lead to mitochondrial trifunctional protein deficiency, a severe metabolic disorder characterized by cardiomyopathy, skeletal myopathy, and life-threatening hypoglycemia [3] OMIM 143450. In clinical pharmacology, HADHB is the primary target of the anti-ischemic drug trimetazidine, which acts as a competitive inhibitor of the long-chain 3-ketoacyl-CoA thiolase [2] DrugBank DB09069. By inhibiting fatty acid oxidation, these metabolic modulators shift myocardial energy production toward glucose oxidation, which requires less oxygen per unit of ATP generated. This shift helps maintain cellular energy levels and protects the myocardium during ischemic events, making HADHB a significant target for treating coronary artery disease.

Other names

Trifunctional enzyme subunit beta, mitochondrial3-ketoacyl-CoA thiolaseTP-betaECHBMitochondrial trifunctional protein subunit betaAcetyl-CoA acyltransferase

Inhibition of long-chain 3-ketoacyl-CoA thiolase activity to shift cardiac metabolism from fatty acid oxidation to glucose oxidation, enhancing ATP production efficiency under ischemic conditions.