Isovaleryl-CoA dehydrogenase (IVD)

Isovaleryl-CoA dehydrogenase (IVD) is a mitochondrial matrix enzyme that catalyzes the third step in the breakdown of the essential amino acid leucine, converting isovaleryl-CoA into 3-methylcrotonyl-CoA[1][4][5][7]. It is a homotetrameric flavoenzyme requiring FAD (flavin adenine dinucleotide) as a cofactor and belongs to the acyl-CoA dehydrogenase family[2][3][7][9]. The enzyme is essential for proper leucine metabolism and energy production; its dysfunction leads to isovaleric acidemia, a rare but serious inherited metabolic disorder marked by acute metabolic crisis, neurological damage, and characteristic biochemical biomarkers[5]. The structure of IVD consists of three distinct domains (two α-helical and one β-sheet), and substrate specificity is conferred by unique residues in the substrate-binding pocket[2][7]. There are no established small molecule drugs that selectively modulate IVD activity; current therapy for deficiencies relies on dietary management and supportive strategies to remove toxic metabolites[5].

Other names

Isovaleryl-CoA dehydrogenase, mitochondrialIVDACAD2IVDHIsovaleryl Coenzyme A dehydrogenaseEpididymis secretory sperm binding protein (rare/outdated)Butyryl-CoA dehydrogenase (misapplied, not advised)

Glycine and L-carnitine: facilitate detoxification and removal of isovaleric acid and related metabolites from accumulation in case of IVD deficiency