The Enzyme Database

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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-methyl-propanoylating)
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-oxo acid dehydrogenase system family, which also includes the pyruvate dehydrogenase system, 2-oxoglutarate dehydrogenase system, and glycine cleavage system. With the exception of the glycine cleavage system, the 2-oxo acid dehydrogenase systems share a common structure, consisting of three main components, namely a 2-oxo acid 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. [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. [PMID: 11477096]
[EC 1.2.1.25 created 1972, modified 2019]
 
 
EC 1.2.4.1     
Accepted name: pyruvate dehydrogenase (acetyl-transferring)
Reaction: pyruvate + [dihydrolipoyllysine-residue acetyltransferase] lipoyllysine = [dihydrolipoyllysine-residue acetyltransferase] S-acetyldihydrolipoyllysine + CO2
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): pyruvate decarboxylase (ambiguous); pyruvate dehydrogenase (ambiguous); pyruvate dehydrogenase (lipoamide); pyruvate:lipoamide 2-oxidoreductase (decarboxylating and acceptor-acetylating); pyruvic acid dehydrogenase; pyruvic dehydrogenase (ambiguous)
Systematic name: pyruvate:[dihydrolipoyllysine-residue acetyltransferase]-lipoyllysine 2-oxidoreductase (decarboxylating, acceptor-acetylating)
Comments: Contains thiamine diphosphate. It is a component (in multiple copies) of the multienzyme pyruvate dehydrogenase complex in which it is bound to a core of molecules of EC 2.3.1.12, dihydrolipoyllysine-residue acetyltransferase, 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 2.3.1.12.
Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, PDB, CAS registry number: 9014-20-4
References:
1.  Ochoa, S. Enzymic mechanisms in the citric acid cycle. Adv. Enzymol. Relat. Subj. Biochem. 15 (1954) 183–270. [PMID: 13158180]
2.  Scriba, P. and Holzer, H. Gewinnung von αHydroxyäthyl-2-thiaminpyrophosphat mit Pyruvatoxydase aus Schweineherzmuskel. Biochem. Z. 334 (1961) 473–486. [PMID: 13749426]
3.  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]
[EC 1.2.4.1 created 1961, modified 2003]
 
 
EC 1.2.4.2     
Accepted name: oxoglutarate dehydrogenase (succinyl-transferring)
Reaction: 2-oxoglutarate + [dihydrolipoyllysine-residue succinyltransferase] lipoyllysine = [dihydrolipoyllysine-residue succinyltransferase] S-succinyldihydrolipoyllysine + CO2
For diagram of the citric-acid cycle, click here and 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-ketoglutarate dehydrogenase; 2-oxoglutarate dehydrogenase; 2-oxoglutarate: lipoate oxidoreductase; 2-oxoglutarate:lipoamide 2-oxidoreductase (decarboxylating and acceptor-succinylating); α-ketoglutarate dehydrogenase; alphaketoglutaric acid dehydrogenase; α-ketoglutaric dehydrogenase; α-oxoglutarate dehydrogenase; AKGDH; OGDC; ketoglutaric dehydrogenase; oxoglutarate decarboxylase (misleading); oxoglutarate dehydrogenase; oxoglutarate dehydrogenase (lipoamide)
Systematic name: 2-oxoglutarate:[dihydrolipoyllysine-residue succinyltransferase]-lipoyllysine 2-oxidoreductase (decarboxylating, acceptor-succinylating)
Comments: Contains thiamine diphosphate. It is a component of the multienzyme 2-oxoglutarate dehydrogenase complex in which multiple copies of it are bound to a core of molecules of EC 2.3.1.61, dihydrolipoyllysine-residue succinyltransferase, 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 2.3.1.61.
Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, PDB, CAS registry number: 9031-02-1
References:
1.  Massey, V. The composition of the ketoglutarate dehydrogenase complex. Biochim. Biophys. Acta 38 (1960) 447–460. [DOI] [PMID: 14422131]
2.  Ochoa, S. Enzymic mechanisms in the citric acid cycle. Adv. Enzymol. Relat. Subj. Biochem. 15 (1954) 183–270. [PMID: 13158180]
3.  Sanadi, D.R., Littlefield, J.W. and Bock, R.M. Studies on α-ketoglutaric oxidase. II. Purification and properties. J. Biol. Chem. 197 (1952) 851–862. [PMID: 12981117]
4.  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]
[EC 1.2.4.2 created 1961, modified 1980, modified 1986, modified 2003]
 
 
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
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]
[EC 1.2.4.4 created 1972 (EC 1.2.4.3 created 1972, incorporated 1978), modified 2003]
 
 
EC 1.4.4.2     
Accepted name: glycine dehydrogenase (aminomethyl-transferring)
Reaction: glycine + [glycine-cleavage complex H protein]-N6-lipoyl-L-lysine = [glycine-cleavage complex H protein]-S-aminomethyl-N6-dihydrolipoyl-L-lysine + CO2
For diagram of glycine cleavage system, click here
Glossary: dihydrolipoyl group
Other name(s): P-protein; glycine decarboxylase; glycine-cleavage complex; glycine:lipoylprotein oxidoreductase (decarboxylating and acceptor-aminomethylating); protein P1; glycine dehydrogenase (decarboxylating); glycine cleavage system P-protein; glycine-cleavage complex P-protein
Systematic name: glycine:H-protein-lipoyllysine oxidoreductase (decarboxylating, acceptor-amino-methylating)
Comments: A pyridoxal-phosphate protein. A component of the glycine cleavage system, which is composed of four components that only loosely associate: the P protein (EC 1.4.4.2), the T protein (EC 2.1.2.10, aminomethyltransferase), the L protein (EC 1.8.1.4, dihydrolipoyl dehydrogenase) and the lipoyl-bearing H protein [3]. Previously known as glycine synthase.
Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, PDB, CAS registry number: 37259-67-9
References:
1.  Hiraga, K. and Kikuchi, G. The mitochondrial glycine cleavage system. Functional association of glycine decarboxylase and aminomethyl carrier protein. J. Biol. Chem. 255 (1980) 11671–11676. [PMID: 7440563]
2.  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]
3.  Nesbitt, N.M., Baleanu-Gogonea, C., Cicchillo, R.M., Goodson, K., Iwig, D.F., Broadwater, J.A., Haas, J.A., Fox, B.G. and Booker, S.J. Expression, purification, and physical characterization of Escherichia coli lipoyl(octanoyl)transferase. Protein Expr. Purif. 39 (2005) 269–282. [DOI] [PMID: 15642479]
[EC 1.4.4.2 created 1984, modified 2003, modified 2006, modified 2013]
 
 
EC 1.6.4.3      
Transferred entry: dihydrolipoamide reductase (NAD+). Now EC 1.8.1.4, dihydrolipoyl dehydrogenase
[EC 1.6.4.3 created 1961, modified 1976, deleted 1983]
 
 
EC 1.8.1.4     
Accepted name: dihydrolipoyl dehydrogenase
Reaction: protein N6-(dihydrolipoyl)lysine + NAD+ = protein N6-(lipoyl)lysine + NADH + H+
For diagram of glycine cleavage system, click here, for diagram of the citric acid cycle, click here and for diagram of oxo-acid dehydrogenase complexes, click here
Glossary: dihydrolipoyl = (6R)-6,8-disulfanyloctanoyl
For structure of dihydrolipoyl, click here
Other name(s): LDP-Glc; LDP-Val; dehydrolipoate dehydrogenase; diaphorase; dihydrolipoamide dehydrogenase; dihydrolipoamide:NAD+ oxidoreductase; dihydrolipoic dehydrogenase; dihydrothioctic dehydrogenase; lipoamide dehydrogenase (NADH); lipoamide oxidoreductase (NADH); lipoamide reductase; lipoamide reductase (NADH); lipoate dehydrogenase; lipoic acid dehydrogenase; lipoyl dehydrogenase; protein-6-N-(dihydrolipoyl)lysine:NAD+ oxidoreductase
Systematic name: protein-N6-(dihydrolipoyl)lysine:NAD+ oxidoreductase
Comments: A flavoprotein (FAD). A component of the multienzyme 2-oxo-acid dehydrogenase complexes. In the pyruvate dehydrogenase complex, it binds to the core of EC 2.3.1.12, dihydrolipoyllysine-residue acetyltransferase, and catalyses oxidation of its dihydrolipoyl groups. It plays a similar role in the oxoglutarate and 3-methyl-2-oxobutanoate dehydrogenase complexes. Another substrate is the dihydrolipoyl group in the H-protein of the glycine-cleavage system (click here for diagram), in which it acts, together with EC 1.4.4.2, glycine dehydrogenase (decarboxylating), and EC 2.1.2.10, aminomethyltransferase, to break down glycine. It can also use free dihydrolipoate, dihydrolipoamide or dihydrolipoyllysine as substrate. This enzyme was first shown to catalyse the oxidation of NADH by methylene blue; this activity was called diaphorase. The glycine cleavage system is composed of four components that only loosely associate: the P protein (EC 1.4.4.2), the T protein (EC 2.1.2.10), the L protein (EC 1.8.1.4) and the lipoyl-bearing H protein [6].
Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, PDB, CAS registry number: 9001-18-7
References:
1.  Massey, V. Lipoyl dehydrogenase. In: Boyer, P.D., Lardy, H. and Myrbäck, K. (Ed.), The Enzymes, 2nd edn, vol. 7, Academic Press, New York, 1963, pp. 275–306.
2.  Massey, V., Gibson, Q.H. and Veeger, C. Intermediates in the catalytic action of lipoyl dehydrogenase (diaphorase). Biochem. J. 77 (1960) 341–351. [PMID: 13767908]
3.  Savage, N. Preparation and properties of highly purified diaphorase. Biochem. J. 67 (1957) 146–155. [PMID: 13471525]
4.  Straub, F.B. Isolation and properties of a flavoprotein from heart muscle tissue. Biochem. J. 33 (1939) 787–792. [PMID: 16746974]
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]
6.  Nesbitt, N.M., Baleanu-Gogonea, C., Cicchillo, R.M., Goodson, K., Iwig, D.F., Broadwater, J.A., Haas, J.A., Fox, B.G. and Booker, S.J. Expression, purification, and physical characterization of Escherichia coli lipoyl(octanoyl)transferase. Protein Expr. Purif. 39 (2005) 269–282. [DOI] [PMID: 15642479]
[EC 1.8.1.4 created 1961 as EC 1.6.4.3, modified 1976, transferred 1983 to EC 1.8.1.4, modified 2003, modified 2006]
 
 
EC 1.11.1.28     
Accepted name: lipoyl-dependent peroxiredoxin
Reaction: a [lipoyl-carrier protein]-N6-[(R)-dihydrolipoyl]-L-lysine + ROOH = a [lipoyl-carrier protein]-N6-lipoyl-L-lysine + H2O + ROH
For diagram of reaction, click here and for mechanism, click here
Other name(s): Ohr; ahpC (gene name); ahpD (gene name)
Systematic name: lipoyl:hydroperoxide oxidoreductase
Comments: Peroxiredoxins (Prxs) are a ubiquitous family of antioxidant proteins. They can be divided into three classes: typical 2-Cys, atypical 2-Cys and 1-Cys peroxiredoxins [2]. The peroxidase reaction comprises two steps centred around a redox-active cysteine called the peroxidatic cysteine. All three peroxiredoxin classes have the first step in common, in which the peroxidatic cysteine attacks the peroxide substrate and is oxidized to S-hydroxycysteine (a sulfenic acid) (see mechanism). The second step of the peroxidase reaction, the regeneration of cysteine from S-hydroxycysteine, distinguishes the three peroxiredoxin classes. For typical 2-Cys Prxs, in the second step, the peroxidatic S-hydroxycysteine from one subunit is attacked by the ‘resolving’ cysteine located in the C-terminus of the second subunit, to form an intersubunit disulfide bond, which is then reduced by one of several cell-specific thiol-containing reductants completing the catalytic cycle. In the atypical 2-Cys Prxs, both the peroxidatic cysteine and its resolving cysteine are in the same polypeptide, so their reaction forms an intrachain disulfide bond. The 1-Cys Prxs conserve only the peroxidatic cysteine, so its regeneration involves direct interaction with a reductant molecule. Two types of lipoyl-dependent peroxiredoxins have been reported from bacteria. One type is the AhpC/AhpD system, originally described from Mycobacterium tuberculosis. In that system, AhpC catalyses reduction of the substrate, resulting in an intramolecular disulfide. AhpD then forms an intermolecular disulfide crosslink with AhpC, reducing it back to active state. AhpD is reduced in turn by lipoylated proteins. The second type, which has been characterized in Xylella fastidiosa, consists of only one type of subunit, which interacts directly with lipoylated proteins.
Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, PDB, UM-BBD, CAS registry number: 207137-51-7
References:
1.  Hillas, P.J., del Alba, F.S., Oyarzabal, J., Wilks, A. and Ortiz De Montellano, P.R. The AhpC and AhpD antioxidant defense system of Mycobacterium tuberculosis. J. Biol. Chem. 275 (2000) 18801–18809. [PMID: 10766746]
2.  Wood, Z.A., Schröder, E., Harris, J.R. and Poole, L.B. Structure, mechanism and regulation of peroxiredoxins. Trends Biochem. Sci. 28 (2003) 32–40. [DOI] [PMID: 12517450]
3.  Koshkin, A., Nunn, C.M., Djordjevic, S. and Ortiz de Montellano, P.R. The mechanism of Mycobacterium tuberculosis alkylhydroperoxidase AhpD as defined by mutagenesis, crystallography, and kinetics. J. Biol. Chem. 278 (2003) 29502–29508. [PMID: 12761216]
4.  Koshkin, A., Knudsen, G.M. and Ortiz De Montellano, P.R. Intermolecular interactions in the AhpC/AhpD antioxidant defense system of Mycobacterium tuberculosis. Arch. Biochem. Biophys. 427 (2004) 41–47. [PMID: 15178486]
5.  Shi, S. and Ehrt, S. Dihydrolipoamide acyltransferase is critical for Mycobacterium tuberculosis pathogenesis. Infect. Immun. 74 (2006) 56–63. [PMID: 16368957]
6.  Cussiol, J.R., Alegria, T.G., Szweda, L.I. and Netto, L.E. Ohr (organic hydroperoxide resistance protein) possesses a previously undescribed activity, lipoyl-dependent peroxidase. J. Biol. Chem. 285 (2010) 21943–21950. [PMID: 20463026]
[EC 1.11.1.28 created 1983 as EC 1.11.1.15, part transferred 2020 to EC 1.11.1.28]
 
 
EC 2.1.2.10     
Accepted name: aminomethyltransferase
Reaction: [protein]-S8-aminomethyldihydrolipoyllysine + tetrahydrofolate = [protein]-dihydrolipoyllysine + 5,10-methylenetetrahydrofolate + NH3
For diagram of the glycine-cleavage system, click here
Glossary: dihydrolipoyl group
Other name(s): S-aminomethyldihydrolipoylprotein:(6S)-tetrahydrofolate aminomethyltransferase (ammonia-forming); T-protein; glycine synthase; tetrahydrofolate aminomethyltransferase; [protein]-8-S-aminomethyldihydrolipoyllysine:tetrahydrofolate aminomethyltransferase (ammonia-forming)
Systematic name: [protein]-S8-aminomethyldihydrolipoyllysine:tetrahydrofolate aminomethyltransferase (ammonia-forming)
Comments: A component, with EC 1.4.4.2 glycine dehydrogenase (decarboxylating) and EC 1.8.1.4, dihydrolipoyl dehydrogenanse, of the glycine cleavage system, formerly known as glycine synthase. The glycine cleavage system is composed of four components that only loosely associate: the P protein (EC 1.4.4.2), the T protein (EC 2.1.2.10), the L protein (EC 1.8.1.4) and the lipoyl-bearing H protein [3].
Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, PDB, CAS registry number: 37257-08-2
References:
1.  Okamura-Ikeda, J., Fujiwara, K. and Motokawa, Y. Purification and characterization of chicken liver T protein, a component of the glycine cleavage system. J. Biol. Chem. 257 (1982) 135–139. [PMID: 7053363]
2.  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]
3.  Nesbitt, N.M., Baleanu-Gogonea, C., Cicchillo, R.M., Goodson, K., Iwig, D.F., Broadwater, J.A., Haas, J.A., Fox, B.G. and Booker, S.J. Expression, purification, and physical characterization of Escherichia coli lipoyl(octanoyl)transferase. Protein Expr. Purif. 39 (2005) 269–282. [DOI] [PMID: 15642479]
[EC 2.1.2.10 created 1972, modified 2003, modified 2006]
 
 
EC 2.3.1.12     
Accepted name: dihydrolipoyllysine-residue acetyltransferase
Reaction: acetyl-CoA + enzyme N6-(dihydrolipoyl)lysine = CoA + enzyme N6-(S-acetyldihydrolipoyl)lysine
For diagram of oxo-acid-dehydrogenase complexes, click here
Glossary: dihydrolipoyl group
Other name(s): acetyl-CoA:dihydrolipoamide S-acetyltransferase; dihydrolipoamide S-acetyltransferase; dihydrolipoate acetyltransferase; dihydrolipoic transacetylase; dihydrolipoyl acetyltransferase; lipoate acetyltransferase; lipoate transacetylase; lipoic acetyltransferase; lipoic acid acetyltransferase; lipoic transacetylase; lipoylacetyltransferase; thioltransacetylase A; transacetylase X; enzyme-dihydrolipoyllysine:acetyl-CoA S-acetyltransferase; acetyl-CoA:enzyme 6-N-(dihydrolipoyl)lysine S-acetyltransferase
Systematic name: acetyl-CoA:enzyme N6-(dihydrolipoyl)lysine S-acetyltransferase
Comments: A multimer (24-mer or 60-mer, depending on the source) of this enzyme forms the core of the pyruvate dehydrogenase multienzyme complex, and binds tightly both EC 1.2.4.1, pyruvate dehydrogenase (acetyl-transferring) and EC 1.8.1.4, dihydrolipoyl dehydrogenase. The lipoyl group of this enzyme is reductively acetylated by EC 1.2.4.1, and the only observed direction catalysed by EC 2.3.1.12 is that where the acetyl group is passed to coenzyme A.
Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, PDB, CAS registry number: 9032-29-5
References:
1.  Brady, R.O. and Stadtman, E.R. Enzymatic thioltransacetylation. J. Biol. Chem. 211 (1954) 621–629. [PMID: 13221570]
2.  Gunsalus, I.C. Group transfer and acyl-generating functions of lipoic acid derivatives. In: McElroy, W.D. and Glass, B. (Ed.), A Symposium on the Mechanism of Enzyme Action, Johns Hopkins Press, Baltimore, 1954, pp. 545–580.
3.  Gunsalus, I.C., Barton, L.S. and Gruber, W. Biosynthesis and structure of lipoic acid derivatives. J. Am. Chem. Soc. 78 (1956) 1763–1766.
4.  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]
[EC 2.3.1.12 created 1961, modified 2003]
 
 
EC 2.3.1.61     
Accepted name: dihydrolipoyllysine-residue succinyltransferase
Reaction: succinyl-CoA + enzyme N6-(dihydrolipoyl)lysine = CoA + enzyme N6-(S-succinyldihydrolipoyl)lysine
For diagram of the citric-acid cycle, click here and for diagram of oxo-acid dehydrogenase complexes, click here
Glossary: dihydrolipoyl group
Other name(s): dihydrolipoamide S-succinyltransferase; dihydrolipoamide succinyltransferase; dihydrolipoic transsuccinylase; dihydrolipolyl transsuccinylase; dihydrolipoyl transsuccinylase; lipoate succinyltransferase (Escherichia coli); lipoic transsuccinylase; lipoyl transsuccinylase; succinyl-CoA:dihydrolipoamide S-succinyltransferase; succinyl-CoA:dihydrolipoate S-succinyltransferase; enzyme-dihydrolipoyllysine:succinyl-CoA S-succinyltransferase
Systematic name: succinyl-CoA:enzyme-N6-(dihydrolipoyl)lysine S-succinyltransferase
Comments: A multimer (24-mer) of this enzyme forms the core of the multienzyme complex, and binds tightly both EC 1.2.4.2, oxoglutarate dehydrogenase (succinyl-transferring) and EC 1.8.1.4, dihydrolipoyl dehydrogenase. The lipoyl group of this enzyme is reductively succinylated by EC 1.2.4.2, and the only observed direction catalysed by EC 2.3.1.61 is that where this succinyl group is passed to coenzyme A.
Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, PDB, CAS registry number: 9032-28-4
References:
1.  Derosier, D.J., Oliver, R.M. and Reed, L.J. Crystallization and preliminary structural analysis of dihydrolipoyl transsuccinylase, the core of the 2-oxoglutarate dehydrogenase complex. Proc. Natl. Acad. Sci. USA 68 (1971) 1135–1137. [DOI] [PMID: 4942179]
2.  Reed, L.J. and Cox, D.J. Multienzyme complexes. In: Boyer, P.D. (Ed.), The Enzymes, 3rd edn, vol. 1, Academic Press, New York, 1970, pp. 213–240.
3.  Knapp, J.E., Mitchell, D.T., Yazdi, M.A., Ernst, S.R., Reed, L.J. and Hackert, M.L. Crystal structure of the truncated cubic core component of the Escherichia coli 2-oxoglutarate dehydrogenase multienzyme complex. J. Mol. Biol. 280 (1998) 655–668. [DOI] [PMID: 9677295]
4.  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]
[EC 2.3.1.61 created 1978, modified 2003]
 
 
EC 2.3.1.168     
Accepted name: dihydrolipoyllysine-residue (2-methylpropanoyl)transferase
Reaction: 2-methylpropanoyl-CoA + enzyme N6-(dihydrolipoyl)lysine = CoA + enzyme N6-(S-[2-methylpropanoyl]dihydrolipoyl)lysine
For diagram of oxo-acid-dehydrogenase complexes, click here
Glossary: dihydrolipoyl group
Other name(s): dihydrolipoyl transacylase; enzyme-dihydrolipoyllysine:2-methylpropanoyl-CoA S-(2-methylpropanoyl)transferase; 2-methylpropanoyl-CoA:enzyme-6-N-(dihydrolipoyl)lysine S-(2-methylpropanoyl)transferase
Systematic name: 2-methylpropanoyl-CoA:enzyme-N6-(dihydrolipoyl)lysine S-(2-methylpropanoyl)transferase
Comments: A multimer (24-mer) of this enzyme forms the core of the multienzyme 3-methyl-2-oxobutanoate dehydrogenase complex, and binds tightly both EC 1.2.4.4, 3-methyl-2-oxobutanoate dehydrogenase (2-methylpropanoyl-transferring) and EC 1.8.1.4, dihydrolipoyl dehydrogenase. The lipoyl group of this enzyme is reductively 2-methylpropanoylated by EC 1.2.4.4, and the only observed direction catalysed by EC 2.3.1.168 is that where this 2-methylpropanoyl is passed to coenzyme A. In addition to the 2-methylpropanoyl group, formed when EC 1.2.4.4 acts on the oxoacid that corresponds with valine, this enzyme also transfers the 3-methylbutanoyl and S-2-methylbutanoyl groups, donated to it when EC 1.2.4.4 acts on the oxo acids corresponding with leucine and isoleucine.
Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, PDB, CAS registry number: 102784-26-9
References:
1.  Massey, L.K., Sokatch, J.R. and Conrad, R.S. Branched-chain amino acid catabolism in bacteria. Bacteriol. Rev. 40 (1976) 42–54. [PMID: 773366]
2.  Chuang, D.T., Hu, C.C., Ku, L.S., Niu, W.L., Myers, D.E. and Cox, R.P. Catalytic and structural properties of the dihydrolipoyl transacylase component of bovine branched-chain α-keto acid dehydrogenase. J. Biol. Chem. 259 (1984) 9277–9284. [PMID: 6746648]
3.  Wynn, R.M., Davie, J.R., Zhi, W., Cox, R.P. and Chuang, D.T. In vitro reconstitution of the 24-meric E2 inner core of bovine mitochondrial branched-chain α-keto acid dehydrogenase complex: requirement for chaperonins GroEL and GroES. Biochemistry 33 (1994) 8962–8968. [PMID: 7913832]
4.  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]
[EC 2.3.1.168 created 2003]
 
 
EC 2.3.1.190     
Accepted name: acetoin dehydrogenase
Reaction: acetoin + CoA + NAD+ = acetaldehyde + acetyl-CoA + NADH + H+
Other name(s): acetoin dehydrogenase complex; acetoin dehydrogenase enzyme system; AoDH ES
Systematic name: acetyl-CoA:acetoin O-acetyltransferase
Comments: Requires thiamine diphosphate. This enzyme, which belongs to the family of 2-oxo acid dehydrogenase complexes, catalyses the oxidative-hydrolytic cleavage of acetoin to acetaldehyde and acetyl-CoA in many bacterial strains, both aerobic and anaerobic. The enzyme is composed of multiple copies of three enzymic components: acetoin oxidoreductase (E1), dihydrolipoamide acetyltransferase (E2) and dihydrolipoyl dehydrogenase (E3).
Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc
References:
1.  Priefert, H., Hein, S., Kruger, N., Zeh, K., Schmidt, B. and Steinbuchel, A. Identification and molecular characterization of the Alcaligenes eutrophus H16 aco operon genes involved in acetoin catabolism. J. Bacteriol. 173 (1991) 4056–4071. [DOI] [PMID: 2061286]
2.  Oppermann, F.B. and Steinbuchel, A. Identification and molecular characterization of the aco genes encoding the Pelobacter carbinolicus acetoin dehydrogenase enzyme system. J. Bacteriol. 176 (1994) 469–485. [DOI] [PMID: 8110297]
3.  Kruger, N., Oppermann, F.B., Lorenzl, H. and Steinbuchel, A. Biochemical and molecular characterization of the Clostridium magnum acetoin dehydrogenase enzyme system. J. Bacteriol. 176 (1994) 3614–3630. [DOI] [PMID: 8206840]
4.  Huang, M., Oppermann, F.B. and Steinbuchel, A. Molecular characterization of the Pseudomonas putida 2,3-butanediol catabolic pathway. FEMS Microbiol. Lett. 124 (1994) 141–150. [DOI] [PMID: 7813883]
5.  Huang, M., Oppermann-Sanio, F.B. and Steinbuchel, A. Biochemical and molecular characterization of the Bacillus subtilis acetoin catabolic pathway. J. Bacteriol. 181 (1999) 3837–3841. [PMID: 10368162]
[EC 2.3.1.190 created 2010]
 
 
EC 2.8.1.8     
Accepted name: lipoyl synthase
Reaction: [protein]-N6-(octanoyl)-L-lysine + an [Fe-S] cluster scaffold protein carrying a [4Fe-4S]2+ cluster + 2 S-adenosyl-L-methionine + 2 oxidized [2Fe-2S] ferredoxin + 6 H+ = [protein]-N6-[(R)-dihydrolipoyl]-L-lysine + an [Fe-S] cluster scaffold protein + 2 sulfide + 4 Fe3+ + 2 L-methionine + 2 5′-deoxyadenosine + 2 reduced [2Fe-2S] ferredoxin
Other name(s): lipA (gene name); LS; lipoate synthase; protein 6-N-(octanoyl)lysine:sulfur sulfurtransferase; protein N6-(octanoyl)lysine:sulfur sulfurtransferase; protein N6-(octanoyl)lysine:sulfur-(sulfur carrier) sulfurtransferase
Systematic name: [protein]-N6-(octanoyl)-L-lysine:an [Fe-S] cluster scaffold protein carrying a [4Fe-4S]2+ cluster sulfurtransferase
Comments: This enzyme catalyses the final step in the de-novo biosynthesis of the lipoyl cofactor, the attachment of two sulfhydryl groups to C6 and C8 of a pendant octanoyl chain. It is a member of the ‘AdoMet radical’ (radical SAM) family, all members of which produce the 5′-deoxyadenosin-5′-yl radical and methionine from AdoMet (S-adenosylmethionine) by the addition of an electron from an iron-sulfur centre. The enzyme contains two [4Fe-4S] clusters. The first cluster produces the radicals, which are converted into 5′-deoxyadenosine when they abstract hydrogen atoms from C6 and C8, respectively, leaving reactive radicals at these positions that interact with sulfur atoms within the second (auxiliary) cluster. Having donated two sulfur atoms, the auxiliary cluster is degraded during catalysis, but is regenerated immediately by the transfer of a new cluster from iron-sulfur cluster carrier proteins [8]. Lipoylation is essential for the function of several key enzymes involved in oxidative metabolism, as it converts apoprotein into the biologically active holoprotein. Examples of such lipoylated proteins include pyruvate dehydrogenase (E2 domain), 2-oxoglutarate dehydrogenase (E2 domain), the branched-chain 2-oxoacid dehydrogenases and the glycine cleavage system (H protein) [1,2]. An alternative lipoylation pathway involves EC 6.3.1.20, lipoate—protein ligase, which can lipoylate apoproteins using exogenous lipoic acid (or its analogues) [4].
Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, CAS registry number: 189398-80-9
References:
1.  Cicchillo, R.M. and Booker, S.J. Mechanistic investigations of lipoic acid biosynthesis in Escherichia coli: both sulfur atoms in lipoic acid are contributed by the same lipoyl synthase polypeptide. J. Am. Chem. Soc. 127 (2005) 2860–2861. [DOI] [PMID: 15740115]
2.  Vanden Boom, T.J., Reed, K.E. and Cronan, J.E., Jr. Lipoic acid metabolism in Escherichia coli: isolation of null mutants defective in lipoic acid biosynthesis, molecular cloning and characterization of the E. coli lip locus, and identification of the lipoylated protein of the glycine cleavage system. J. Bacteriol. 173 (1991) 6411–6420. [DOI] [PMID: 1655709]
3.  Zhao, X., Miller, J.R., Jiang, Y., Marletta, M.A. and Cronan, J.E. Assembly of the covalent linkage between lipoic acid and its cognate enzymes. Chem. Biol. 10 (2003) 1293–1302. [DOI] [PMID: 14700636]
4.  Cicchillo, R.M., Iwig, D.F., Jones, A.D., Nesbitt, N.M., Baleanu-Gogonea, C., Souder, M.G., Tu, L. and Booker, S.J. Lipoyl synthase requires two equivalents of S-adenosyl-L-methionine to synthesize one equivalent of lipoic acid. Biochemistry 43 (2004) 6378–6386. [DOI] [PMID: 15157071]
5.  Jordan, S.W. and Cronan, J.E., Jr. A new metabolic link. The acyl carrier protein of lipid synthesis donates lipoic acid to the pyruvate dehydrogenase complex in Escherichia coli and mitochondria. J. Biol. Chem. 272 (1997) 17903–17906. [DOI] [PMID: 9218413]
6.  Miller, J.R., Busby, R.W., Jordan, S.W., Cheek, J., Henshaw, T.F., Ashley, G.W., Broderick, J.B., Cronan, J.E., Jr. and Marletta, M.A. Escherichia coli LipA is a lipoyl synthase: in vitro biosynthesis of lipoylated pyruvate dehydrogenase complex from octanoyl-acyl carrier protein. Biochemistry 39 (2000) 15166–15178. [DOI] [PMID: 11106496]
7.  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]
8.  McCarthy, E.L. and Booker, S.J. Destruction and reformation of an iron-sulfur cluster during catalysis by lipoyl synthase. Science 358 (2017) 373–377. [DOI] [PMID: 29051382]
[EC 2.8.1.8 created 2006, modified 2014, modified 2018]
 
 


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