Mitochondrial trifunctional enzyme subunit beta (HADHB)

Mitochondrial trifunctional enzyme subunit beta (HADHB) is an essential component of the mitochondrial trifunctional protein complex, which catalyzes the final three steps of β-oxidation of long-chain fatty acids in human cells. This enzyme is crucial for the conversion of long-chain fatty acids into acetyl-CoA, a substrate for the citric acid cycle and ATP energy generation. HADHB provides the 3-ketoacyl-CoA thiolase activity of the complex; the alpha subunit (HADHA) provides the other two necessary activities. Mutations in HADHB lead to mitochondrial trifunctional protein deficiency, characterized by the inability to properly metabolize long-chain fatty acids, resulting in lethal metabolic crises, neuropathy, hepatic dysfunction, cardiomyopathy, and unique maternal risks during pregnancy. Management focuses on dietary modifications, as there are currently no direct pharmacologic agents targeting HADHB; diagnosis relies on acylcarnitine analysis and genetic testing[1][2][3][4][6][8].

Other names

Hydroxyacyl-CoA dehydrogenase trifunctional multienzyme complex subunit betaTrifunctional enzyme subunit beta, mitochondrial3-ketoacyl-CoA thiolaseMTPBTP-betaAcetyl-CoA acyltransferaseBeta-ketothiolaseECHB2-enoyl-Coenzyme A hydratase, beta subunitHydroxyacyl-Coenzyme A dehydrogenase/3-ketoacyl-Coenzyme A thiolase/enoyl-Coenzyme A hydratase (trifunctional protein), beta subunitMSTP029MTPDMTPD2TP-BETALong-chain 3-ketoacyl-CoA thiolaseKatLKATMitochondrial long-chain 3-ketoacyl-CoA thiolase[3][5]

Current therapy is dietary management: supplementation with medium-chain triglycerides to bypass the long-chain fatty acid oxidation defect; avoidance of fasting to prevent metabolic crisis. No direct enzyme inhibitors are currently in clinical use for this target.