|Superclasses:||Reactions Classified By Conversion Type → Simple Reactions → Chemical Reactions → Protein-Modification Reactions|
|Reactions Classified By Substrate → Macromolecule Reactions → Protein-Reactions → Protein-Modification Reactions|
EC Number: 22.214.171.124
Enzymes and Genes:
|Bacillus subtilis subtilis 168:||lipoyl synthase (lipoic acid synthetase): lipA|
|Escherichia coli K-12 substr. MG1655:||lipoyl synthase: lipA|
|Saccharomyces cerevisiae:||lipoyl synthase: LIP5|
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): -2.9760284 [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 126.96.36.199, 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 188.8.131.52, lipoate—protein ligase, which can lipoylate apoproteins using exogenous lipoic acid (or its analogues) [Perham00].
Unification Links: KEGG:R07767
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
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
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
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
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