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Pathway Description
Lipoic Acid Metabolism
Escherichia coli
Metabolic Pathway
Lipoic acid metabolism starts with caprylic acid being introduced into the cytoplasm, however, no transporter has been identified yet. i) Once caprylic acid is in the cytoplasm, it can react with a holo-acp through an ATP-driven 2-acylglycerophosphoethanolamine acyltransferase/acyl-ACP synthetase resulting in pyrophosphate, AMP, and octanoyl-[acp]. The latter compound can also be obtained from palmitate biosynthesis. ii) Octanoyl-acp then interacts with a lipoyl-carrier protein L-lysine through an octanoyltransferase resulting in a hydrogen ion, a holo-acyl-acp, and an N6-(octanoyl)lysine. iii) N6-(octanoyl)lysine reacts with an S-adenosylmethionine, a sulfurated[sulfur carrier], and a reduced ferredoxin through a lipoate-protein ligase A, resulting in a 5-deoxyadenosine, an L-methionine, an unsulfurated [sulfur carrier], oxidized ferredoxin, and protein N6-(octanoyl)lysine.
Caprylic acid can also interact with ATP and a lipoyl-carrier protein-L-lysine through a lipoate-protein ligase A resulting in an AMP, pyrophosphate, hydrogen ion, and protein N6-(octanoyl)lysine. The latter compound reacts with an S-adenosylmethionine, a sulfurated[sulfur carrier] and a reduced ferredoxin through a lipoate-protein ligase A, resulting in a 5-deoxyadenosine, an L-methionine, an unsulfurated [sulfur carrier], oxidized ferredoxin, and a protein N6-(octanoyl)lysine.
R-Lipoic acid can be absorbed from the environment, as seen in studies by Morris TW. In this pathway, the lipoyl-protein ligase LplA utilizes pre-existing lipoate that has been imported from outside the cell, and thus catalyzes a salvage pathway. Lipoic acid interacts with ATP and hydrogen ion through a lipoyl-protein ligase A, resulting in a pyrophosphate and a lipoyl-AMP (lipoyl-adenylate). This compound then interacts with a lipoyl-carrier protein-L-lysine through a lipoate-protein ligase A resulting in an AMP, a hydrogen ion, and a protein N6-(lipoyl) lysine. It has been suggested that the conversion of octanoylated-domains into lipoylated ones described in this pathway may be a type of a repair pathway, activated only if the other lipoate biosynthetic pathways are malfunctioning.
References
Lipoic Acid Metabolism References
Frey PA: Radical mechanisms of enzymatic catalysis. Annu Rev Biochem. 2001;70:121-48. doi: 10.1146/annurev.biochem.70.1.121.
Pubmed: 11395404
Herbert AA, Guest JR: Lipoic acid content of Escherichia coli and other microorganisms. Arch Microbiol. 1975 Dec 31;106(3):259-66.
Pubmed: 814874
Marquet A, Bui BT, Florentin D: Biosynthesis of biotin and lipoic acid. Vitam Horm. 2001;61:51-101.
Pubmed: 11153271
Miller JR, Busby RW, Jordan SW, Cheek J, Henshaw TF, Ashley GW, Broderick JB, Cronan JE Jr, Marletta MA: Escherichia coli LipA is a lipoyl synthase: in vitro biosynthesis of lipoylated pyruvate dehydrogenase complex from octanoyl-acyl carrier protein. Biochemistry. 2000 Dec 12;39(49):15166-78.
Pubmed: 11106496
Morris TW, Reed KE, Cronan JE Jr: Lipoic acid metabolism in Escherichia coli: the lplA and lipB genes define redundant pathways for ligation of lipoyl groups to apoprotein. J Bacteriol. 1995 Jan;177(1):1-10.
Pubmed: 8002607
Ollagnier-de Choudens S, Sanakis Y, Hewitson KS, Roach P, Munck E, Fontecave M: Reductive cleavage of S-adenosylmethionine by biotin synthase from Escherichia coli. J Biol Chem. 2002 Apr 19;277(16):13449-54. doi: 10.1074/jbc.M111324200. Epub 2002 Feb 7.
Pubmed: 11834738
Reed LJ, Hackert ML: Structure-function relationships in dihydrolipoamide acyltransferases. J Biol Chem. 1990 Jun 5;265(16):8971-4.
Pubmed: 2188967
Reed KE, Cronan JE Jr: Lipoic acid metabolism in Escherichia coli: sequencing and functional characterization of the lipA and lipB genes. J Bacteriol. 1993 Mar;175(5):1325-36.
Pubmed: 8444795
Stepp LR, Bleile DM, McRorie DK, Pettit FH, Reed LJ: Use of trypsin and lipoamidase to study the role of lipoic acid moieties in the pyruvate and alpha-ketoglutarate dehydrogenase complexes of Escherichia coli. Biochemistry. 1981 Aug 4;20(16):4555-60.
Pubmed: 6794598
Vanden Boom TJ, Reed KE, Cronan JE 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. 1991 Oct;173(20):6411-20.
Pubmed: 1655709
Zhao X, Miller JR, Jiang Y, Marletta MA, Cronan JE: Assembly of the covalent linkage between lipoic acid and its cognate enzymes. Chem Biol. 2003 Dec;10(12):1293-302.
Pubmed: 14700636
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