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 |
1.1.1.272 |
Accepted name: |
D-2-hydroxyacid dehydrogenase (NADP+) |
Reaction: |
an (R)-2-hydroxycarboxylate + NADP+ = a 2-oxocarboxylate + NADPH + H+ |
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For diagram of coenzyme M biosynthesis, click here |
Other name(s): |
ddh (gene name) |
Systematic name: |
(R)-2-hydroxycarboxylate:NADP+ oxidoreductase |
Comments: |
This enzyme, characterized from the halophilic archaeon Haloferax mediterranei and the mold Aspergillus oryzae, catalyses a stereospecific reduction of 2-oxocarboxylic acids into the corresponding D-2-hydroxycarboxylic acids. The enzyme prefers substrates with a main chain of 5 carbons (such as 4-methyl-2-oxopentanoate) to those with a shorter chain, and can use NADH with much lower efficiency. cf. EC 1.1.1.345, (D)-2-hydroxyacid dehydrogenase (NAD+). |
Links to other databases: |
BRENDA, EXPASY, KEGG, MetaCyc, PDB, CAS registry number: 81210-65-3 |
References: |
1. |
Domenech, J. and Ferrer, J. A new D-2-hydroxyacid dehydrogenase with dual coenzyme-specificity from Haloferax mediterranei, sequence analysis and heterologous overexpression. Biochim. Biophys. Acta 1760 (2006) 1667–1674. [DOI] [PMID: 17049749] |
2. |
Shimizu, M., Yamamoto, T., Okabe, N., Sakai, K., Koide, E., Miyachi, Y., Kurimoto, M., Mochizuki, M., Yoshino-Yasuda, S., Mitsui, S., Ito, A., Murano, H., Takaya, N. and Kato, M. Novel 4-methyl-2-oxopentanoate reductase involved in synthesis of the Japanese sake flavor, ethyl leucate. Appl. Microbiol. Biotechnol. (2015) . [DOI] [PMID: 26615399] |
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[EC 1.1.1.272 created 2002, modified 2013] |
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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 |
1.2.1.25 |
Accepted name: |
branched-chain α-keto acid dehydrogenase system |
Reaction: |
3-methyl-2-oxobutanoate + CoA + NAD+ = 2-methylpropanoyl-CoA + CO2 + NADH |
Other name(s): |
branched-chain α-keto acid dehydrogenase complex; 2-oxoisovalerate dehydrogenase; α-ketoisovalerate dehydrogenase; 2-oxoisovalerate dehydrogenase (acylating) |
Systematic name: |
3-methyl-2-oxobutanoate:NAD+ 2-oxidoreductase (CoA-methylpropanoylating) |
Comments: |
This enzyme system catalyses the oxidative decarboxylation of branched-chain α-keto acids derived from L-leucine, L-isoleucine, and L-valine to branched-chain acyl-CoAs. It belongs to the 2-oxoacid dehydrogenase system family, which also includes EC 1.2.1.104, pyruvate dehydrogenase system, EC 1.2.1.105, 2-oxoglutarate dehydrogenase system, EC 1.4.1.27, glycine cleavage system, and EC 2.3.1.190, acetoin dehydrogenase system. With the exception of the glycine cleavage system, which contains 4 components, the 2-oxoacid dehydrogenase systems share a common structure, consisting of three main components, namely a 2-oxoacid dehydrogenase (E1), a dihydrolipoamide acyltransferase (E2), and dihydrolipoamide dehydrogenase (E3). The reaction catalysed by this system is the sum of three activities: EC 1.2.4.4, 3-methyl-2-oxobutanoate dehydrogenase (2-methylpropanoyl-transferring), EC 2.3.1.168, dihydrolipoyllysine-residue (2-methylpropanoyl)transferase, and EC 1.8.1.4, dihydrolipoyl dehydrogenase. The system also acts on (S)-3-methyl-2-oxopentanoate and 4-methyl-2-oxopentanoate. |
Links to other databases: |
BRENDA, EXPASY, KEGG, MetaCyc, CAS registry number: 37211-61-3 |
References: |
1. |
Namba, Y., Yoshizawa, K., Ejima, A., Hayashi, T. and Kaneda, T. Coenzyme A- and nicotinamide adenine dinucleotide-dependent branched chain α-keto acid dehydrogenase. I. Purification and properties of the enzyme from Bacillus subtilis. J. Biol. Chem. 244 (1969) 4437–4447. [PMID: 4308861] |
2. |
Pettit, F.H., Yeaman, S.J. and Reed, L.J. Purification and characterization of branched chain α-keto acid dehydrogenase complex of bovine kidney. Proc. Natl. Acad. Sci. USA 75 (1978) 4881–4885. [DOI] [PMID: 283398] |
3. |
Harris, R.A., Hawes, J.W., Popov, K.M., Zhao, Y., Shimomura, Y., Sato, J., Jaskiewicz, J. and Hurley, T.D. Studies on the regulation of the mitochondrial α-ketoacid dehydrogenase complexes and their kinases. Adv. Enzyme Regul. 37 (1997) 271–293. [DOI] [PMID: 9381974] |
4. |
Evarsson, A., Chuang, J.L., Wynn, R.M., Turley, S., Chuang, D.T. and Hol, W.G. Crystal structure of human branched-chain α-ketoacid dehydrogenase and the molecular basis of multienzyme complex deficiency in maple syrup urine disease. Structure 8 (2000) 277–291. [PMID: 10745006] |
5. |
Reed, L.J. A trail of research from lipoic acid to α-keto acid dehydrogenase complexes. J. Biol. Chem. 276 (2001) 38329–38336. [DOI] [PMID: 11477096] |
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[EC 1.2.1.25 created 1972, modified 2019, modified 2020] |
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EC |
1.2.4.4 |
Accepted name: |
3-methyl-2-oxobutanoate dehydrogenase (2-methylpropanoyl-transferring) |
Reaction: |
3-methyl-2-oxobutanoate + [dihydrolipoyllysine-residue (2-methylpropanoyl)transferase] lipoyllysine = [dihydrolipoyllysine-residue (2-methylpropanoyl)transferase] S-(2-methylpropanoyl)dihydrolipoyllysine + CO2 |
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For diagram of oxo-acid-dehydrogenase complexes, click here |
Glossary: |
dihydrolipoyl group
thiamine diphosphate = 3-[(4-amino-2-methylpyrimidin-5-yl)methyl]-5-(2-diphosphoethyl)-4-methyl-1,3-thiazolium |
Other name(s): |
2-oxoisocaproate dehydrogenase; 2-oxoisovalerate (lipoate) dehydrogenase; 3-methyl-2-oxobutanoate dehydrogenase (lipoamide); 3-methyl-2-oxobutanoate:lipoamide oxidoreductase (decarboxylating and acceptor-2-methylpropanoylating); α-keto-α-methylvalerate dehydrogenase; α-ketoisocaproate dehydrogenase; α-ketoisocaproic dehydrogenase; α-ketoisocaproic-α-keto-α-methylvaleric dehydrogenase; α-ketoisovalerate dehydrogenase; α-oxoisocaproate dehydrogenase; BCKDH (ambiguous); BCOAD; branched chain keto acid dehydrogenase; branched-chain (-2-oxoacid) dehydrogenase (BCD); branched-chain 2-keto acid dehydrogenase; branched-chain 2-oxo acid dehydrogenase; branched-chain α-keto acid dehydrogenase; branched-chain α-oxo acid dehydrogenase; branched-chain keto acid dehydrogenase; branched-chain ketoacid dehydrogenase; dehydrogenase, 2-oxoisovalerate (lipoate); dehydrogenase, branched chain α-keto acid |
Systematic name: |
3-methyl-2-oxobutanoate:[dihydrolipoyllysine-residue (2-methylpropanoyl)transferase]-lipoyllysine 2-oxidoreductase (decarboxylating, acceptor-2-methylpropanoylating) |
Comments: |
Contains thiamine diphosphate. It acts not only on 3-methyl-2-oxobutanaoate, but also on 4-methyl-2-oxopentanoate and (S)-3-methyl-2-oxopentanoate, so that it acts on the 2-oxo acids that derive from the action of transaminases on valine, leucine and isoleucine. It is a component of the multienzyme 3-methyl-2-oxobutanoate dehydrogenase complex in which multiple copies of it are bound to a core of molecules of EC 2.3.1.168, dihydrolipoyllysine-residue (2-methylpropanoyl)transferase, which also binds multiple copies of EC 1.8.1.4, dihydrolipoyl dehydrogenase. It does not act on free lipoamide or lipoyllysine, but only on the lipoyllysine residue in EC 2.3.1.168. |
Links to other databases: |
BRENDA, EXPASY, KEGG, MetaCyc, PDB, CAS registry number: 9082-72-8 |
References: |
1. |
Bowden, J.A. and Connelly, J.L. Branched chain α-keto acid metabolism. II. Evidence for the common identity of α-ketoisocaproic acid and α-keto-β-methyl-valeric acid dehydrogenases. J. Biol. Chem. 243 (1968) 3526–3531. [PMID: 5656388] |
2. |
Connelly, J.L., Danner, D.J. and Bowden, J.A. Branched chain α-keto acid metabolism. I. Isolation, purification, and partial characterization of bovine liver α-ketoisocaproic:α-keto-β-methylvaleric acid dehydrogenase. J. Biol. Chem. 243 (1968) 1198–1203. [PMID: 5689906] |
3. |
Danner, D.J., Lemmon, S.K., Beharse, J.C. and Elsas, L.J., II Purification and characterization of branched chain α-ketoacid dehydrogenase from bovine liver mitochondria. J. Biol. Chem. 254 (1979) 5522–5526. [PMID: 447664] |
4. |
Pettit, F.H., Yeaman, S.J. and Reed, L.J. Purification and characterization of branched chain α-keto acid dehydrogenase complex of bovine kidney. Proc. Natl. Acad. Sci. USA 75 (1978) 4881–4885. [DOI] [PMID: 283398] |
5. |
Perham, R.N. Swinging arms and swinging domains in multifunctional enzymes: catalytic machines for multistep reactions. Annu. Rev. Biochem. 69 (2000) 961–1004. [DOI] [PMID: 10966480] |
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[EC 1.2.4.4 created 1972 (EC 1.2.4.3 created 1972, incorporated 1978), modified 2003] |
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EC |
1.4.1.9 |
Accepted name: |
leucine dehydrogenase |
Reaction: |
L-leucine + H2O + NAD+ = 4-methyl-2-oxopentanoate + NH3 + NADH + H+ |
Other name(s): |
L-leucine dehydrogenase; L-leucine:NAD+ oxidoreductase, deaminating; LeuDH |
Systematic name: |
L-leucine:NAD+ oxidoreductase (deaminating) |
Comments: |
Also acts on isoleucine, valine, norvaline and norleucine. |
Links to other databases: |
BRENDA, EXPASY, GTD, KEGG, MetaCyc, PDB, CAS registry number: 9082-71-7 |
References: |
1. |
Sanwal, B.D. and Zink, M.W. L-Leucine dehydrogenase of Bacillus cereus. Arch. Biochem. Biophys. 94 (1961) 430–435. [DOI] [PMID: 13746411] |
2. |
Zink, M.W. and Sanwal, B.D. The distribution and substrate specificity of L-leucine dehydrogenase. Arch. Biochem. Biophys. 99 (1962) 72–77. |
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[EC 1.4.1.9 created 1972] |
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EC
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2.3.1.182
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Transferred entry: | (R)-citramalate synthase. Now classified as EC 2.3.3.21, (R)-citramalate synthase.
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[EC 2.3.1.182 created 2007, deleted 2021] |
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EC |
2.3.3.21 |
Accepted name: |
(R)-citramalate synthase |
Reaction: |
acetyl-CoA + pyruvate + H2O = CoA + (2R)-2-hydroxy-2-methylbutanedioate |
Glossary: |
(2R)-2-hydroxy-2-methylbutanedioate = (2R)-2-methylmalate = (–)-citramalate
3-methyl-2-oxobutanoate = α-ketoisovalerate
2-oxobutanoate = α-ketobutyrate
4-methyl-2-oxopentanoate = α-ketoisocaproate
2-oxohexanoate = α-ketopimelate
2-oxoglutarate = α-ketoglutarate |
Other name(s): |
CimA |
Comments: |
One of the enzymes involved in a pyruvate-derived pathway for isoleucine biosynthesis that is found in some bacterial and archaeal species [1,2]. The enzyme can be inhibited by isoleucine, the end-product of the pathway, but not by leucine [2]. The enzyme is highly specific for pyruvate as substrate, as the 2-oxo acids 3-methyl-2-oxobutanoate, 2-oxobutanoate, 4-methyl-2-oxopentanoate, 2-oxohexanoate and 2-oxoglutarate cannot act as substrate [1,2]. |
Links to other databases: |
BRENDA, EXPASY, KEGG, MetaCyc |
References: |
1. |
Howell, D.M., Xu, H. and White, R.H. (R)-citramalate synthase in methanogenic archaea. J. Bacteriol. 181 (1999) 331–333. [DOI] [PMID: 9864346] |
2. |
Xu, H., Zhang, Y., Guo, X., Ren, S., Staempfli, A.A., Chiao, J., Jiang, W. and Zhao, G. Isoleucine biosynthesis in Leptospira interrogans serotype 1ai strain 56601 proceeds via a threonine-independent pathway. J. Bacteriol. 186 (2004) 5400–5409. [DOI] [PMID: 15292141] |
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[EC 2.3.3.21 created 2007 as EC 2.3.1.182, transferred 2021 to EC 2.3.3.21] |
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EC |
2.6.1.6 |
Accepted name: |
leucine transaminase |
Reaction: |
L-leucine + 2-oxoglutarate = 4-methyl-2-oxopentanoate + L-glutamate |
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For diagram of reaction, click here, for diagram of leucine biosynthesis, click here and for diagram of mechanism, click here |
Other name(s): |
L-leucine aminotransferase; leucine 2-oxoglutarate transaminase; leucine aminotransferase; leucine-α-ketoglutarate transaminase |
Systematic name: |
L-leucine:2-oxoglutarate aminotransferase |
Comments: |
A pyridoxal-phosphate protein. This enzyme differs from EC 2.6.1.42, branched-chain-amino-acid transaminase, in that it does not act on L-valine or L-isoleucine, although it does act on L-methionine. The mitochondrial form from rat liver differs in physical characteristics from the cytoplasmic form. |
Links to other databases: |
BRENDA, EXPASY, KEGG, MetaCyc, CAS registry number: 9030-37-9 |
References: |
1. |
Aki, K., Ogawa, K. and Ichihara, A. Transaminases of branched chain amino acids. IV. Purification and properties of two enzymes from rat liver. Biochim. Biophys. Acta 159 (1968) 276–284. [DOI] [PMID: 4968655] |
2. |
Ikeda, T., Konishi, Y. and Ichihara, A. Transaminase of branched chain amino acids. XI. Leucine (methionine) transaminase of rat liver mitochondria. Biochim. Biophys. Acta 445 (1976) 622–631. [DOI] [PMID: 974100] |
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[EC 2.6.1.6 created 1961, modified 1982] |
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EC |
2.6.1.42 |
Accepted name: |
branched-chain-amino-acid transaminase |
Reaction: |
L-leucine + 2-oxoglutarate = 4-methyl-2-oxopentanoate + L-glutamate |
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For diagram of reaction, click here, of leucine biosynthesis click here, of isoleucine and valine biosynthesis, click here, of coenzyme-A biosynthesis, click here and for diagram of mechanism, click here |
Other name(s): |
transaminase B; branched-chain amino acid aminotransferase; branched-chain amino acid-glutamate transaminase; branched-chain aminotransferase; L-branched chain amino acid aminotransferase; glutamate-branched-chain amino acid transaminase |
Systematic name: |
branched-chain-amino-acid:2-oxoglutarate aminotransferase |
Comments: |
Also acts on L-isoleucine and L-valine, and thereby differs from EC 2.6.1.6, leucine transaminase, which does not. It also differs from EC 2.6.1.66, valine—pyruvate transaminase. |
Links to other databases: |
BRENDA, EXPASY, KEGG, MetaCyc, PDB, CAS registry number: 9054-65-3 |
References: |
1. |
Aki, K., Ogawa, K. and Ichihara, A. Transaminases of branched chain amino acids. IV. Purification and properties of two enzymes from rat liver. Biochim. Biophys. Acta 159 (1968) 276–284. [DOI] [PMID: 4968655] |
2. |
Aki, K., Yokojima, A. and Ichihara, A. Transaminase of branched chain amino acids. VI. Purification and properties of the hog brain enzyme. J. Biochem. (Tokyo) 65 (1969) 539–544. [PMID: 4979711] |
3. |
Ichihara, A. and Koyama, E. Transaminase of branched chain amino acids. I. Branched chain amino acids-α-ketoglutarate transaminase. J. Biochem. (Tokyo) 59 (1966) 160–169. [PMID: 5943594] |
4. |
Taylor, R.T. and Jenkins, W.T. Leucine aminotransferase. II. Purification and characterization. J. Biol. Chem. 241 (1966) 4396–4405. [PMID: 5922965] |
5. |
Rudman, D. and Meister, A. Transamination in Escherichia coli. J. Biol. Chem. 200 (1953) 591–604. [PMID: 13034817] |
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[EC 2.6.1.42 created 1972] |
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