3-isopropylmalate dehydrogenase (IPMDH) (IPMDH)

3-isopropylmalate dehydrogenase (IPMDH) is a key enzyme in the biosynthetic pathway of the branched-chain amino acid leucine, found in bacteria, fungi, and plants (UniProt, 2024). It catalyzes the NAD+-dependent oxidative decarboxylation of 3-isopropylmalate to 2-oxoisocaproate, a critical step that precedes the final transamination to leucine (Wikipedia, 2024). Since humans and other mammals lack the leucine biosynthesis pathway and must obtain this amino acid through their diet, IPMDH is considered an attractive target for the development of novel antimicrobial and antifungal therapies (PubMed, 2014). Inhibition of this enzyme effectively starves the pathogen of an essential nutrient, leading to growth arrest. Research has identified several experimental inhibitors, such as O-methyl oxalohydroxamate and 3-methylmercaptomalate, which show potency against the enzyme in pathogens like Mycobacterium tuberculosis (PubMed, 2014). Beyond clinical applications, IPMDH is also a target for herbicidal compounds, such as O-isobutenyl oxalylhydroxamate, as blocking leucine synthesis in plants results in significant growth inhibition (PMC, 1992).

Other names

3-IPM-DHBeta-isopropylmalate dehydrogenaseBeta-IPM dehydrogenaseIMDHleuBLEU2

Inhibition of the oxidative decarboxylation of 3-isopropylmalate to 2-ketoisocaproic acid, thereby blocking the biosynthesis of the essential amino acid leucine.