EC |
1.1.1.85 |
Accepted name: |
3-isopropylmalate dehydrogenase |
Reaction: |
(2R,3S)-3-isopropylmalate + NAD+ = 4-methyl-2-oxopentanoate + CO2 + NADH + H+ (overall reaction) (1a) (2R,3S)-3-isopropylmalate + NAD+ = (2S)-2-isopropyl-3-oxosuccinate + NADH + H+ (1b) (2S)-2-isopropyl-3-oxosuccinate = 4-methyl-2-oxopentanoate + CO2 (spontaneous) |
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For diagram of leucine biosynthesis, click here |
Other name(s): |
β-isopropylmalic enzyme; β-isopropylmalate dehydrogenase; threo-Ds-3-isopropylmalate dehydrogenase; 3-carboxy-2-hydroxy-4-methylpentanoate:NAD+ oxidoreductase |
Systematic name: |
(2R,3S)-3-isopropylmalate:NAD+ oxidoreductase |
Comments: |
The product decarboxylates spontaneously to yield 4-methyl-2-oxopentanoate. |
Links to other databases: |
BRENDA, EXPASY, KEGG, MetaCyc, PDB, CAS registry number: 9030-97-1 |
References: |
1. |
Burns, R.O., Umbarger, H.E. and Gross, S.R. The biosynthesis of leucine. III. The conversion of α-hydroxy-β-carboxyisocaproate to α-ketoisocaproate. Biochemistry 2 (1963) 1053. [PMID: 14087358] |
2. |
Parsons, S.J. and Burns, R.O. Purification and properties of β-isopropylmalate dehydrogenase. J. Biol. Chem. 244 (1969) 996–1003. [PMID: 4889950] |
3. |
Németh, A., Svingor, Á., Pócsik, M., Dobó, J., Magyar, C, Szilaaagyi, A., Gál, P. and Závodszky, P. Mirror image mutations reveal the significance of an intersubunit ion cluster in the stability of 3-isopropylmalate dehydrogenase. FEBS Lett. 468 (2000) 48–52. [DOI] [PMID: 10683439] |
4. |
Calvo, J. M., Stevens, C. M., Kalyanpur, M. G., and Umbarger, H. E. The absolute configuration of α-hydroxy-β-carboxyisocaproic acid (3-isopropylmalic acid), an intermediate in leucine biosynthesis. Biochemistry 3 (1964) 2024–2027. [PMID: 14269331] |
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[EC 1.1.1.85 created 1972, modified 1976] |
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EC |
1.1.1.345 |
Accepted name: |
D-2-hydroxyacid dehydrogenase (NAD+) |
Reaction: |
an (R)-2-hydroxycarboxylate + NAD+ = a 2-oxocarboxylate + NADH + H+ |
Other name(s): |
LdhA; HdhD; D-2-hydroxyisocaproate dehydrogenase; R-HicDH; D-HicDH; (R)-2-hydroxy-4-methylpentanoate:NAD+ oxidoreductase; (R)-2-hydroxyisocaproate dehydrogenase; D-mandelate dehydrogenase (ambiguous) |
Systematic name: |
(R)-2-hydroxycarboxylate:NAD+ oxidoreductase |
Comments: |
The enzymes, characterized from bacteria (Peptoclostridium difficile, Enterococcus faecalis and from lactic acid bacteria) prefer substrates with a main chain of 5 carbons (such as 4-methyl-2-oxopentanoate) to those with a shorter chain. It also utilizes phenylpyruvate. The enzyme from the halophilic archaeon Haloferax mediterranei prefers substrates with a main chain of 3-4 carbons (pyruvate and 2-oxobutanoate). cf. EC 1.1.1.272, (D)-2-hydroxyacid dehydrogenase (NADP+). |
Links to other databases: |
BRENDA, EXPASY, KEGG, MetaCyc |
References: |
1. |
Dengler, U., Niefind, K., Kiess, M. and Schomburg, D. Crystal structure of a ternary complex of D-2-hydroxyisocaproate dehydrogenase from Lactobacillus casei, NAD+ and 2-oxoisocaproate at 1.9 Å resolution. J. Mol. Biol. 267 (1997) 640–660. [DOI] [PMID: 9126843] |
2. |
Bonete, M.J., Ferrer, J., Pire, C., Penades, M. and Ruiz, J.L. 2-Hydroxyacid dehydrogenase from Haloferax mediterranei, a D-isomer-specific member of the 2-hydroxyacid dehydrogenase family. Biochimie 82 (2000) 1143–1150. [DOI] [PMID: 11120357] |
3. |
Kim, J., Darley, D., Selmer, T. and Buckel, W. Characterization of (R)-2-hydroxyisocaproate dehydrogenase and a family III coenzyme A transferase involved in reduction of L-leucine to isocaproate by Clostridium difficile. Appl. Environ. Microbiol. 72 (2006) 6062–6069. [DOI] [PMID: 16957230] |
4. |
Wada, Y., Iwai, S., Tamura, Y., Ando, T., Shinoda, T., Arai, K. and Taguchi, H. A new family of D-2-hydroxyacid dehydrogenases that comprises D-mandelate dehydrogenases and 2-ketopantoate reductases. Biosci. Biotechnol. Biochem. 72 (2008) 1087–1094. [DOI] [PMID: 18391442] |
5. |
Chambellon, E., Rijnen, L., Lorquet, F., Gitton, C., van Hylckama Vlieg, J.E., Wouters, J.A. and Yvon, M. The D-2-hydroxyacid dehydrogenase incorrectly annotated PanE is the sole reduction system for branched-chain 2-keto acids in Lactococcus lactis. J. Bacteriol. 191 (2009) 873–881. [DOI] [PMID: 19047348] |
6. |
Miyanaga, A., Fujisawa, S., Furukawa, N., Arai, K., Nakajima, M. and Taguchi, H. The crystal structure of D-mandelate dehydrogenase reveals its distinct substrate and coenzyme recognition mechanisms from those of 2-ketopantoate reductase. Biochem. Biophys. Res. Commun. 439 (2013) 109–114. [DOI] [PMID: 23954635] |
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[EC 1.1.1.345 created 2013] |
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EC |
2.3.3.13 |
Accepted name: |
2-isopropylmalate synthase |
Reaction: |
acetyl-CoA + 3-methyl-2-oxobutanoate + H2O = (2S)-2-isopropylmalate + CoA |
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For diagram of leucine-biosynthesis pathway, click here |
Other name(s): |
3-carboxy-3-hydroxy-4-methylpentanoate 3-methyl-2-oxobutanoate-lyase (CoA-acetylating); α-isopropylmalate synthetase; α-isopropylmalate synthase; α-isopropylmalic synthetase; isopropylmalate synthase; isopropylmalate synthetase |
Systematic name: |
acetyl-CoA:3-methyl-2-oxobutanoate C-acetyltransferase (thioester-hydrolysing, carboxymethyl-forming) |
Comments: |
Requires K+. |
Links to other databases: |
BRENDA, EXPASY, KEGG, MetaCyc, PDB, CAS registry number: 9030-98-2 |
References: |
1. |
Kohlhaw, G., Leary, T.R. and Umbarger, H.E. α-Isopropylmalate synthase from Salmonella typhimurium. Purification and properties. J. Biol. Chem. 244 (1969) 2218–2225. [PMID: 4976555] |
2. |
Webster, R.E. and Gross, S.R. The α-isopropylmalate synthetase of Neurospora. I. The kinetics and end product control of α-isopropylmalate synthetase function. Biochemistry 4 (1965) 2309–2327. |
3. |
Cole, F.E., Kalyanpur, M. G. and Stevens, C. M. Absolute configuration of α-isopropylmalate and the mechanism of its conversion to β-isopropylmalate in the biosynthesis of leucine. Biochemistry 12 (1973) 3346–3350. [PMID: 4270046] |
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[EC 2.3.3.13 created 1972 as EC 4.1.3.12, transferred 2002 to EC 2.3.3.13] |
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EC |
2.8.3.5 |
Accepted name: |
3-oxoacid CoA-transferase |
Reaction: |
succinyl-CoA + a 3-oxo acid = succinate + a 3-oxoacyl-CoA |
Other name(s): |
3-oxoacid coenzyme A-transferase; 3-ketoacid CoA-transferase; 3-ketoacid coenzyme A transferase; 3-oxo-CoA transferase; 3-oxoacid CoA dehydrogenase; acetoacetate succinyl-CoA transferase; acetoacetyl coenzyme A-succinic thiophorase; succinyl coenzyme A-acetoacetyl coenzyme A-transferase; succinyl-CoA transferase |
Systematic name: |
succinyl-CoA:3-oxo-acid CoA-transferase |
Comments: |
Acetoacetate and, more slowly, 3-oxopropanoate, 3-oxopentanoate, 3-oxo-4-methylpentanoate or 3-oxohexanoate can act as acceptors; malonyl-CoA can act instead of succinyl-CoA. |
Links to other databases: |
BRENDA, EAWAG-BBD, EXPASY, GTD, KEGG, MetaCyc, PDB, CAS registry number: 9027-43-4 |
References: |
1. |
Hersh, L.B. and Jencks, W.P. Coenzyme A transferase. Kinetics and exchange reactions. J. Biol. Chem. 242 (1967) 3468–3480. |
2. |
Lynen, F. and Ochoa, S. Enzymes of fatty acid metabolism. Biochim. Biophys. Acta 12 (1953) 299–314. [DOI] [PMID: 13115439] |
3. |
Menon, G.K.K. and Stern, J.R. Enzymic synthesis and metabolism of malonyl coenzyme A and glutaryl coenzyme A. J. Biol. Chem. 235 (1960) 3393–3398. [PMID: 13769479] |
4. |
Stern, J.R., Coon, M.J., del Campillo, A. and Schneider, M.C. Enzymes of fatty acid metabolism. IV. Preparation and properties of coenzyme A transferase. J. Biol. Chem. 221 (1956) 15–31. [PMID: 13345795] |
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[EC 2.8.3.5 created 1961, modified 1980] |
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EC |
2.8.3.24 |
Accepted name: |
(R)-2-hydroxy-4-methylpentanoate CoA-transferase |
Reaction: |
4-methylpentanoyl-CoA + (R)-2-hydroxy-4-methylpentanoate = 4-methylpentanoate + (R)-2-hydroxy-4-methylpentanoyl-CoA |
Glossary: |
4-methylpentanoate = isocaproate |
Other name(s): |
hadA (gene name) |
Systematic name: |
4-methylpentanoyl-CoA:(R)-2-hydroxy-4-methylpentanoate CoA-transferase |
Comments: |
The enzyme, characterized from the bacterium Peptoclostridium difficile, participates in an L-leucine fermentation pathway. The reaction proceeds via formation of a covalent anhydride intermediate between a conserved aspartate residue and the acyl group of the CoA thioester substrate. |
Links to other databases: |
BRENDA, EXPASY, KEGG, MetaCyc |
References: |
1. |
Kim, J., Darley, D., Selmer, T. and Buckel, W. Characterization of (R)-2-hydroxyisocaproate dehydrogenase and a family III coenzyme A transferase involved in reduction of L-leucine to isocaproate by Clostridium difficile. Appl. Environ. Microbiol. 72 (2006) 6062–6069. [DOI] [PMID: 16957230] |
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[EC 2.8.3.24 created 2016] |
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