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MetaCyc Reaction:

Superclasses: Reactions Classified By Conversion TypeSimple ReactionsChemical ReactionsProtein-Modification Reactions
Reactions Classified By SubstrateMacromolecule ReactionsProtein-ReactionsProtein-Modification Reactions

EC Number:

Enzymes and Genes:

Bacillus subtilis subtilis 168: lipoyl synthase (lipoic acid synthetase)Inferred from experiment: lipA
Escherichia coli K-12 substr. MG1655: lipoyl synthaseInferred from experiment: lipA
Saccharomyces cerevisiae: lipoyl synthaseInferred from experiment: LIP5

In Pathway: lipoate biosynthesis and incorporation II, lipoate biosynthesis and incorporation I, lipoate biosynthesis and incorporation III (Bacillus)

The direction shown, i.e. which substrates are on the left and right sides, is in accordance with the Enzyme Commission system.

Mass balance status: Balanced.

Enzyme Commission Primary Name: lipoyl synthase

Enzyme Commission Synonyms: LS, LipA, lipoate synthase, protein 6-N-(octanoyl)lysine:sulfur sulfurtransferase, protein N6-(octanoyl)lysine:sulfur sulfurtransferase

Standard Gibbs Free Energy (ΔrG in kcal/mol): -2.9760284Inferred by computational analysis [Latendresse13]

Enzyme Commission Summary:
This enzyme 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 [i.e. S-adenosylmethionine, or S-(5'-deoxyadenosin-5'-yl)methionine], by the addition of an electron from an iron-sulfur centre. The radical is converted into 5'-deoxyadenosine when it abstracts a hydrogen atom from C-6 and C-8, leaving reactive radicals at these positions so that they can add sulfur, with inversion of configuration [Cicchillo04a]. This enzyme catalyses the final step in the de-novo biosynthesis of the lipoyl cofactor, with the other enzyme involved being EC, lipoyl(octanoyl) transferase. 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) [Vanden91, Jordan97]. An alternative lipoylation pathway involves EC, lipoate—protein ligase, which can lipoylate apoproteins using exogenous lipoic acid (or its analogues) [Perham00].

Citations: [Cicchillo05, Zhao03, Frey01, Miller00a]

Gene-Reaction Schematic

Gene-Reaction Schematic

Unification Links: KEGG:R07767

Relationship Links: BRENDA:EC:, ENZYME:EC:, IUBMB-ExplorEnz:EC:


Cicchillo04a: Cicchillo RM, Iwig DF, Jones AD, Nesbitt NM, Baleanu-Gogonea C, Souder MG, Tu L, Booker SJ (2004). "Lipoyl synthase requires two equivalents of S-adenosyl-L-methionine to synthesize one equivalent of lipoic acid." Biochemistry 43(21);6378-86. PMID: 15157071

Cicchillo05: Cicchillo RM, Booker SJ (2005). "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(9);2860-1. PMID: 15740115

Frey01: Frey PA (2001). "Radical mechanisms of enzymatic catalysis." Annu Rev Biochem 70;121-48. PMID: 11395404

Jordan97: Jordan SW, Cronan JE (1997). "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(29);17903-6. PMID: 9218413

Latendresse13: Latendresse M. (2013). "Computing Gibbs Free Energy of Compounds and Reactions in MetaCyc."

Miller00a: Miller JR, Busby RW, Jordan SW, Cheek J, Henshaw TF, Ashley GW, Broderick JB, Cronan JE, Marletta MA (2000). "Escherichia coli LipA is a lipoyl synthase: in vitro biosynthesis of lipoylated pyruvate dehydrogenase complex from octanoyl-acyl carrier protein." Biochemistry 39(49);15166-78. PMID: 11106496

Perham00: Perham RN (2000). "Swinging arms and swinging domains in multifunctional enzymes: catalytic machines for multistep reactions." Annu Rev Biochem 69;961-1004. PMID: 10966480

Vanden91: Vanden Boom TJ, Reed KE, Cronan JE (1991). "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(20);6411-20. PMID: 1655709

Zhao03: Zhao X, Miller JR, Jiang Y, Marletta MA, Cronan JE (2003). "Assembly of the covalent linkage between lipoic acid and its cognate enzymes." Chem Biol 10(12);1293-302. PMID: 14700636

Report Errors or Provide Feedback
Please cite the following article in publications resulting from the use of MetaCyc: Caspi et al, Nucleic Acids Research 42:D459-D471 2014
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