Hydroxyacyl-CoA dehydrogenase, mitochondrial (HADH)

Hydroxyacyl-CoA dehydrogenase, mitochondrial (HADH) is a mitochondrial enzyme essential for the beta-oxidation of short-chain fatty acids, specifically catalyzing the conversion of 3-hydroxyacyl-CoA to 3-oxoacyl-CoA using NAD+ as a cofactor (UniProt Q01857). In addition to its metabolic role, HADH is a key regulator of insulin secretion in pancreatic beta cells; it physically interacts with and inhibits glutamate dehydrogenase (GDH), thereby preventing overstimulation of insulin release (PubMed: 15994892). Genetic mutations in the HADH gene are the primary cause of familial hyperinsulinemic hypoglycemia type 4 (HHF4), a condition where patients experience profound hypoglycemia due to dysregulated insulin secretion (OMIM: 609975). This enzyme is considered a therapeutic target in the context of metabolic research and the management of congenital hyperinsulinism. While direct pharmacological activators are not currently in standard clinical use, the pathway is managed using drugs like diazoxide, which counteracts the hyperinsulinism resulting from HADH deficiency (StatPearls: NBK537154). Understanding HADH function is crucial for developing treatments for fatty acid oxidation disorders and hyperinsulinemic states.

Other names

L-3-hydroxyacyl-CoA dehydrogenaseShort-chain 3-hydroxyacyl-CoA dehydrogenaseSCHADHADHSCHCDHMedium and short-chain L-3-hydroxyacyl-coenzyme A dehydrogenase

Catalyzes the NAD+-dependent oxidation of 3-hydroxyacyl-CoA to 3-oxoacyl-CoA and regulates insulin secretion by inhibiting glutamate dehydrogenase.