3-hydroxyacyl-CoA dehydrogenase (HADH) (HADH)

3-hydroxyacyl-CoA dehydrogenase (HADH) is a mitochondrial enzyme that plays a central role in the fatty acid beta-oxidation pathway, specifically catalyzing the oxidation of short-chain 3-hydroxyacyl-CoAs to their corresponding 3-oxoacyl-CoAs [1][2]. This reaction is NAD+-dependent and is a critical step in the breakdown of fats for cellular energy production [1]. Beyond its metabolic function, HADH is a key regulator of insulin secretion in pancreatic beta cells [3]. It exerts this control by inhibiting the enzyme glutamate dehydrogenase (GDH), thereby preventing inappropriate insulin release in response to amino acids [4]. Mutations in the HADH gene lead to 3-hydroxyacyl-CoA dehydrogenase deficiency, which manifests as familial hyperinsulinemic hypoglycemia [5]. While there are currently no approved drugs that directly target HADH, it is a significant biomarker in newborn screening and a subject of research for metabolic and endocrine disorders [6]. The enzyme's dual role in lipid metabolism and hormonal regulation makes it a protein of high interest for understanding systemic energy balance [7].

Other names

L-3-hydroxybutyryl-CoA dehydrogenaseShort-chain 3-hydroxyacyl-CoA dehydrogenaseSCHADHADHSC3-hydroxyacyl-Coenzyme A dehydrogenase3-hydroxybutyryl-CoA dehydrogenase

Catalyzes the NAD+-dependent oxidation of 3-hydroxyacyl-CoA to 3-oxoacyl-CoA.