3-hydroxyacyl-CoA dehydrogenase type-2 (HADH2)

3-hydroxyacyl-CoA dehydrogenase type-2 (HADH2, also known as 17β-HSD10 or HSD17B10) is a mitochondrial enzyme central to multiple metabolic processes, including fatty acid beta-oxidation (specifically the reversible conversion of (S)-3-hydroxyacyl-CoA to 3-ketoacyl-CoA), branched-chain amino acid degradation, and steroid and neurosteroid metabolism[2][3][4][5][7][9]. It is essential for energy production from medium- and short-chain fatty acids, especially in tissues with high energy requirements such as the brain, heart, liver, and muscle. Additionally, it plays a non-metabolic role as a component of mitochondrial RNase P, necessary for mitochondrial tRNA processing, and has been implicated in neurodegenerative disorders through its interaction with amyloid-beta. Pathogenic defects in HADH2 result in various inborn errors of metabolism and have been associated with neurodegeneration and neurological disease[9][1][7].

Other names

17-beta-hydroxysteroid dehydrogenase type 10 (17β-HSD10)3-hydroxyacyl-CoA dehydrogenase type II3-hydroxy-2-methylbutyryl-CoA dehydrogenaseMHBDEndoplasmic reticulum-associated amyloid beta-peptide-binding protein (ERAB)Mitochondrial ribonuclease P protein 2 (MRPP2)L-3-hydroxyacyl-CoA dehydrogenase type 2Short-chain L-3-hydroxyacyl-CoA dehydrogenase (SCHAD)HSD17B10

Drugs or compounds act as substrates or inhibitors of the enzyme's dehydrogenase activity, either modulating mitochondrial fatty acid oxidation, branched-chain amino acid metabolism, or neuroactive steroid turnover[9]. The enzyme oxidizes allopregnanolone at the 3α-hydroxyl group, thereby influencing gamma-aminobutyric acid (GABA) receptor modulation[7][9].