EC |
1.1.1.84 |
Accepted name: |
dimethylmalate dehydrogenase |
Reaction: |
(R)-3,3-dimethylmalate + NAD+ = 3-methyl-2-oxobutanoate + CO2 + NADH |
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For diagram of pantothenate catabolism, click here |
Other name(s): |
β,β-dimethylmalate dehydrogenase |
Systematic name: |
(R)-3,3-dimethylmalate:NAD+ oxidoreductase (decarboxylating) |
Comments: |
Requires K+ or NH4+ and Mn2+ or Co2+; also acts on (R)-malate. |
Links to other databases: |
BRENDA, EXPASY, KEGG, MetaCyc, CAS registry number: 37250-21-8 |
References: |
1. |
Magee, P.T. and Snell, E.E. The bacterial degradation of pantothenic acid. IV. Enzymatic conversion of aldopantoate to α-ketoisovalerate. Biochemistry 5 (1966) 409–416. [PMID: 4287371] |
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[EC 1.1.1.84 created 1972] |
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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 |
1.2.1.33 |
Accepted name: |
(R)-dehydropantoate dehydrogenase |
Reaction: |
(R)-4-dehydropantoate + NAD+ + H2O = (R)-3,3-dimethylmalate + NADH + 2 H+ |
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For diagram of pantothenate catabolism, click here |
Other name(s): |
D-aldopantoate dehydrogenase; D-2-hydroxy-3,3-dimethyl-3-formylpropionate:diphosphopyridine nucleotide (DPN+) oxidoreductase |
Systematic name: |
(R)-4-dehydropantoate:NAD+ 4-oxidoreductase |
Links to other databases: |
BRENDA, EXPASY, KEGG, MetaCyc, CAS registry number: 37250-96-7 |
References: |
1. |
Magee, P.T. and Snell, E.E. The bacterial degradation of pantothenic acid. IV. Enzymatic conversion of aldopantoate to α-ketoisovalerate. Biochemistry 5 (1966) 409–416. [PMID: 4287371] |
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[EC 1.2.1.33 created 1972] |
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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 |
2.1.2.11 |
Accepted name: |
3-methyl-2-oxobutanoate hydroxymethyltransferase |
Reaction: |
5,10-methylenetetrahydrofolate + 3-methyl-2-oxobutanoate + H2O = tetrahydrofolate + 2-dehydropantoate |
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For diagram of the early stages of CoA biosynthesis, click here |
Other name(s): |
α-ketoisovalerate hydroxymethyltransferase; dehydropantoate hydroxymethyltransferase; ketopantoate hydroxymethyltransferase; oxopantoate hydroxymethyltransferase; 5,10-methylene tetrahydrofolate:α-ketoisovalerate hydroxymethyltransferase |
Systematic name: |
5,10-methylenetetrahydrofolate:3-methyl-2-oxobutanoate hydroxymethyltransferase |
Links to other databases: |
BRENDA, EXPASY, KEGG, MetaCyc, PDB, CAS registry number: 56093-17-5 |
References: |
1. |
Powers, S.G. and Snell, E.E. Ketopantoate hydroxymethyltransferase. II. Physical, catalytic, and regulatory properties. J. Biol. Chem. 251 (1976) 3786–3793. [PMID: 6463] |
2. |
Teller, J.H., Powers, S.G. and Snell, E.E. Ketopantoate hydroxymethyltransferase. I. Purification and role in pantothenate biosynthesis. J. Biol. Chem. 251 (1976) 3780–3785. [PMID: 776976] |
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[EC 2.1.2.11 created 1982] |
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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 |
2.6.1.66 |
Accepted name: |
valine—pyruvate transaminase |
Reaction: |
L-valine + pyruvate = 3-methyl-2-oxobutanoate + L-alanine |
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For diagram of reaction, click here, of isoleucine and valine biosynthesis, click here and for diagram of mechanism, click here |
Other name(s): |
transaminase C; valine-pyruvate aminotransferase; alanine-oxoisovalerate aminotransferase |
Systematic name: |
L-valine:pyruvate aminotransferase |
Comments: |
Different from EC 2.6.1.42, branched-chain-amino-acid-transaminase. |
Links to other databases: |
BRENDA, EXPASY, KEGG, MetaCyc, PDB, CAS registry number: 73379-50-7 |
References: |
1. |
Falkinham, J.O. , III Identification of a mutation affecting an alanine-α-ketoisovalerate transaminase activity in Escherichia coli K-12. Mol. Gen. Genet. 176 (1979) 147–149. [PMID: 396446] |
2. |
Rudman, D. and Meister, A. Transamination in Escherichia coli. J. Biol. Chem. 200 (1953) 591–604. [PMID: 13034817] |
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[EC 2.6.1.66 created 1984] |
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EC |
4.1.1.72 |
Accepted name: |
branched-chain-2-oxoacid decarboxylase |
Reaction: |
(3S)-3-methyl-2-oxopentanoate = 2-methylbutanal + CO2 |
Other name(s): |
branched-chain oxo acid decarboxylase; branched-chain α-keto acid decarboxylase; branched-chain keto acid decarboxylase; BCKA; (3S)-3-methyl-2-oxopentanoate carboxy-lyase |
Systematic name: |
(3S)-3-methyl-2-oxopentanoate carboxy-lyase (2-methylbutanal-forming) |
Comments: |
Acts on a number of 2-oxo acids, with a high affinity towards branched-chain substrates. The aldehyde formed may be enzyme-bound, and may be an intermediate in the bacterial system for the biosynthesis of branched-chain fatty acids. |
Links to other databases: |
BRENDA, EXPASY, KEGG, MetaCyc, PDB, CAS registry number: 63653-19-0 |
References: |
1. |
Oku, H. and Kaneda, T. Biosynthesis of branched-chain fatty acids in Bacillus subtilis. A decarboxylase is essential for branched-chain fatty acid synthetase. J. Biol. Chem. 263 (1988) 18386–18396. [PMID: 3142877] |
2. |
de la Plaza, M., Fernandez de Palencia, P., Pelaez, C. and Requena, T. Biochemical and molecular characterization of α-ketoisovalerate decarboxylase, an enzyme involved in the formation of aldehydes from amino acids by Lactococcus lactis. FEMS Microbiol. Lett. 238 (2004) 367–374. [PMID: 15358422] |
3. |
Smit, B.A., van Hylckama Vlieg, J.E., Engels, W.J., Meijer, L., Wouters, J.T. and Smit, G. Identification, cloning, and characterization of a Lactococcus lactis branched-chain α-keto acid decarboxylase involved in flavor formation. Appl. Environ. Microbiol. 71 (2005) 303–311. [PMID: 15640202] |
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[EC 4.1.1.72 created 1990] |
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