Parent Class:

EC-Numbers → 1 -- Oxidoreductases → 1.1 -- Acting on the CH-OH group of donors → 1.1.1 -- With NAD(+) or NADP(+) as acceptor

Synonyms: β-isopropylmalic enzyme, β-isopropylmalate dehydrogenase, threo-D_s-3-isopropylmalate dehydrogenase, 3-carboxy-2-hydroxy-4-methylpentanoate:NAD⁺ oxidoreductase

Systematic Name: (2R,3S)-3-isopropylmalate:NAD⁺ oxidoreductase

Unification Links: BRENDA:1.1.1.85, ENZYME:1.1.1.85, IUBMB-ExplorEnz:1.1.1.85

Reaction:
(2R,3S)-3-isopropylmalate + NAD⁺ → 4-methyl-2-oxopentanoate + CO₂ + NADH

Unofficial Reactions:
3-[(5'-methylsulfanyl)pentyl]malate + NAD⁺ → 8-(methylsulfanyl)-2-oxooctanoate + CO₂ + NADH,
3-[(6'-methylsulfanyl)hexyl]malate + NAD⁺ → 9-(methylsulfanyl)-2-oxononanoate + CO₂ + NADH,
3-[(7'-methylsulfanyl)heptyl]malate + NAD⁺ → 10-(methylsulfanyl)-2-oxodecanoate + CO₂ + NADH,
3-ethylmalate + NAD⁺ → 2-oxovalerate + CO₂ + NADH,
3-[(4'-methylsulfanyl)butyl]malate + NAD⁺ → 7-(methylsulfanyl)-2-oxoheptanoate + CO₂ + NADH,
3-[(3'-methylsulfanyl)propyl]malate + NAD⁺ → 6-(methylsulfanyl)-2-oxohexanoate + CO₂ + NADH

Enzymes and Genes:
3-isopropylmalate dehydrogenase: leuB ( Escherichia coli K-12 substr. MG1655 )
D-malate/3-isopropylmalate dehydrogenase (decarboxylating): dmlA ( Escherichia coli K-12 substr. MG1655 )
2-benzyl-3-hydroxybutanedioate dehydrogenase: hphB ( Nostoc punctiforme PCC 73102 )
3-methylmalate dehydrogenase / 3-isopropylmalate dehydrogenase: MJ0720 ( Methanocaldococcus jannaschii )
β-isopropylmalate dehydrogenase: leuB ( Leptospira interrogans serovar Lai str. 56601 )
3-isopropylmalate dehydrogenase: LEU2 ( Saccharomyces cerevisiae )
isopropylmalate dehydrogenase 3: IMDH3 ( Arabidopsis thaliana col )

Summary:
The product decarboxylates spontaneously to yield 4-methyl-2-oxopentanoate.

Citations: [Burns63, Calvo64, Parsons69, Nemeth00]

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References

Burns63: Burns RO, Umbarger HE, Gross SR (1963). "The biosynthesis of leucine. Iii. The conversion of alpha-hydroxy-beta-carboxyisocaproate to alpha-ketoisocaproate." Biochemistry 2;1053-8. PMID: 14087358

Calvo64: Calvo JM, Stevens CM, KalyanpurMG, Umbarger HE (1964). "The absolute configuration of alpha-hydroxy-beta-carboxyisocaproic acid (3-isopropylmalic acid), an intermediate in leucine biosynthesis." Biochemistry 3;2024-7. PMID: 14269331

Nemeth00: Nemeth A, Svingor A, Pocsik M, Dobo J, Magyar C, Szilagyi A, Gal P, Zavodszky P (2000). "Mirror image mutations reveal the significance of an intersubunit ion cluster in the stability of 3-isopropylmalate dehydrogenase." FEBS Lett 468(1);48-52. PMID: 10683439

Parsons69: Parsons SJ, Burns RO (1969). "Purification and properties of beta-isopropylmalate dehydrogenase." J Biol Chem 1969;244(3);996-1003. PMID: 4889950

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Please cite the following article in publications resulting from the use of MetaCyc: Caspi et al, Nucleic Acids Research 46(D1):D633-D639 2018
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