Hydroxyacyl-CoA dehydrogenase trifunctional multienzyme complex subunit beta (HADHB) (HADHB)

Hydroxyacyl-CoA dehydrogenase trifunctional multienzyme complex subunit beta (HADHB) is a mitochondrial enzyme that constitutes the beta subunit of the mitochondrial trifunctional protein (MTP) (UniProt: P55084). It is responsible for the thiolase activity in the long-chain fatty acid beta-oxidation pathway, specifically catalyzing the final step where 3-ketoacyl-CoA is cleaved into acetyl-CoA and a shorter acyl-CoA (NCBI Gene: 3032). Deficiencies in HADHB lead to mitochondrial trifunctional protein deficiency, a condition characterized by life-threatening metabolic crises, cardiomyopathy, and neuropathy (OMIM: 609015). In a therapeutic context, HADHB is targeted by drugs like trimetazidine, which inhibits its thiolase activity to shift cardiac metabolism toward glucose oxidation, thereby improving oxygen efficiency in ischemic heart disease (PubMed: 11508905). Additionally, it is a primary candidate for gene therapy approaches aimed at restoring metabolic function in patients with inherited MTP deficiencies (PubMed: 25503444). The protein functions as a hetero-octamer with HADHA, and its proper assembly is essential for mitochondrial energy production from lipids.

Other names

3-ketoacyl-CoA thiolase, mitochondrialAcetyl-CoA acyltransferaseBeta-ketothiolaseMitochondrial trifunctional protein subunit betaTP-betaECHBMSTP029

Competitive inhibition of the 3-ketoacyl-CoA thiolase activity to reduce fatty acid oxidation and promote glucose oxidation.