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MetaCyc Pathway: lipoate salvage I

Enzyme View:

Pathway diagram: lipoate salvage I

This view shows enzymes only for those organisms listed below, in the list of taxa known to possess the pathway. If an enzyme name is shown in bold, there is experimental evidence for this enzymatic activity.

Superclasses: Biosynthesis Cofactors, Prosthetic Groups, Electron Carriers Biosynthesis Lipoate Biosynthesis

Some taxa known to possess this pathway include ? : Bacillus subtilis subtilis 168 , Escherichia coli K-12 substr. MG1655 , Thermoplasma acidophilum

Expected Taxonomic Range: Archaea , Bacteria , Fungi , Metazoa

Summary:
About lipoate

(R)-lipoate is a sulfur-containing cofactor found in many prokaryotic and eukaryotic organisms. It is utilized by several enzymes involved in oxidative metabolism, including the pyruvate dehydrogenase complex [Herbert75, Stepp81, Reed93], the 2-oxoglutarate decarboxylation to succinyl-CoA [Herbert75, Stepp81, Reed93], the 2-oxoisovalerate decarboxylation to isobutanoyl-CoA [Reed90], and the glycine cleavage [Vanden91, Reed93].

Each of these enzyme complexes is composed of multiple copies of three enzymes: a substrate-specific decarboxylase-dehydrogenase (E1), a dihydrolipoamide acyltransferase (E2) specific for each type of complex, and a dihydrolipoamide dehydrogenase (E3), a flavoprotein that is a common component of these multienzyme complexes. E1 catalyzes both the decarboxylation of the α-keto acid and the subsequent reductive acylation of the lipoyl moiety, which is covalently bound to E2. E2 catalyzes the acyl transfer step, and E3 catalyzes the reoxidation of the dihydrolipoyl moiety with NAD as the ultimate electron acceptor [Reed90]. The lipoate cofactor is bound to the E2 by an amide linkage between its carboxylate moiety and a specific lysine residue in the enzyme [Reed93].

About This Pathway

In this pathway the enzyme lipoate-protein ligase A (LplA, LplB or LplJ, depending on strain) attaches pre-existing lipoate that has been imported from outside the cell to an E2 enzyme, thus catalyzing a salvage pathway [Morris95]. The pathway has been shown to occur in archaea [Christensen09], bacteria [Morris94, Morris95] and animals [Fujiwara99, Fujiwara01].

It is generally believed that mammals primarily rely on salvaged (R)-lipoate. Even though the genes encoding LipA and LipB have been identified in mammalian genomes, and it has been shown that mammalian cells are capable of synthesizing (R)-lipoate in mitochondria [Morikawa01], their significance is not fully understood. The ligation of salvaged (R)-lipoate in mammals is performed by a single enzyme, LplA (lipoate protein ligase A), which catalyzes both the activation of (R)-lipoate to a lipoyl-adenylate intermediate, and the ligation of the later to the E2 subunits, as described here [Fujiwara99, Fujiwara01]. A similar enzyme has been characterized in bacteria [Morris94, Morris95].

In most Archaea the enzyme that catalyzes these reactions is a heterodimer, composed of proteins encoded by lplA and lplB genes [Christensen09]. LplB is required for lipoyl-adenylate formation but is not required for transfer of the lipoyl moiety of lipoyl-adenylate to acceptor proteins [Christensen09].

For the de novo synthesis of lipoate from octanoate or octanoyl-[acp], see lipoate biosynthesis and incorporation I and lipoate biosynthesis and incorporation II.

Variants: lipoate biosynthesis and incorporation (glycine cleavage system, yeast) , lipoate biosynthesis and incorporation (pyruvate dehydrogenase and oxoglutarate dehydrogenase, yeast) , lipoate biosynthesis and incorporation I , lipoate biosynthesis and incorporation II , lipoate biosynthesis and incorporation III (Bacillus) , lipoate salvage II

Unification Links: EcoCyc:PWY0-522

Credits:
Created 02-Apr-2003 by Arnaud M , SRI International
Revised 08-May-2006 by Caspi R , SRI International


References

Christensen09: Christensen QH, Cronan JE (2009). "The Thermoplasma acidophilum LplA-LplB complex defines a new class of bipartite lipoate-protein ligases." J Biol Chem 284(32);21317-26. PMID: 19520844

Fujiwara01: Fujiwara K, Takeuchi S, Okamura-Ikeda K, Motokawa Y (2001). "Purification, characterization, and cDNA cloning of lipoate-activating enzyme from bovine liver." J Biol Chem 276(31);28819-23. PMID: 11382754

Fujiwara99: Fujiwara K, Suzuki M, Okumachi Y, Okamura-Ikeda K, Fujiwara T, Takahashi E, Motokawa Y (1999). "Molecular cloning, structural characterization and chromosomal localization of human lipoyltransferase gene." Eur J Biochem 260(3);761-7. PMID: 10103005

Herbert75: Herbert AA, Guest JR (1975). "Lipoic acid content of Escherichia coli and other microorganisms." Arch Microbiol 106(3);259-66. PMID: 814874

Morikawa01: Morikawa T, Yasuno R, Wada H (2001). "Do mammalian cells synthesize lipoic acid? Identification of a mouse cDNA encoding a lipoic acid synthase located in mitochondria." FEBS Lett 498(1);16-21. PMID: 11389890

Morris94: Morris TW, Reed KE, Cronan JE (1994). "Identification of the gene encoding lipoate-protein ligase A of Escherichia coli. Molecular cloning and characterization of the lplA gene and gene product." J Biol Chem 269(23);16091-100. PMID: 8206909

Morris95: Morris TW, Reed KE, Cronan JE (1995). "Lipoic acid metabolism in Escherichia coli: the lplA and lipB genes define redundant pathways for ligation of lipoyl groups to apoprotein." J Bacteriol 177(1);1-10. PMID: 8002607

Reed90: Reed LJ, Hackert ML (1990). "Structure-function relationships in dihydrolipoamide acyltransferases." J Biol Chem 265(16);8971-4. PMID: 2188967

Reed93: Reed KE, Cronan JE (1993). "Lipoic acid metabolism in Escherichia coli: sequencing and functional characterization of the lipA and lipB genes." J Bacteriol 175(5);1325-36. PMID: 8444795

Stepp81: Stepp LR, Bleile DM, McRorie DK, Pettit FH, Reed LJ (1981). "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 20(16);4555-60. PMID: 6794598

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

Other References Related to Enzymes, Genes, Subpathways, and Substrates of this Pathway

Brookfield91: Brookfield DE, Green J, Ali ST, Machado RS, Guest JR (1991). "Evidence for two protein-lipoylation activities in Escherichia coli." FEBS Lett 295(1-3);13-6. PMID: 1765143

Christensen11: Christensen QH, Hagar JA, O'Riordan MX, Cronan JE (2011). "A complex lipoate utilization pathway in Listeria monocytogenes." J Biol Chem 286(36);31447-56. PMID: 21768091

Christensen11a: Christensen QH, Martin N, Mansilla MC, de Mendoza D, Cronan JE (2011). "A novel amidotransferase required for lipoic acid cofactor assembly in Bacillus subtilis." Mol Microbiol 80(2);350-63. PMID: 21338421

Cronan05: Cronan JE, Zhao X, Jiang Y (2005). "Function, attachment and synthesis of lipoic acid in Escherichia coli." Adv Microb Physiol 50;103-46. PMID: 16221579

DiazMejia09: Diaz-Mejia JJ, Babu M, Emili A (2009). "Computational and experimental approaches to chart the Escherichia coli cell-envelope-associated proteome and interactome." FEMS Microbiol Rev 33(1);66-97. PMID: 19054114

Fujiwara05: Fujiwara K, Toma S, Okamura-Ikeda K, Motokawa Y, Nakagawa A, Taniguchi H (2005). "Crystal structure of lipoate-protein ligase A from Escherichia coli. Determination of the lipoic acid-binding site." J Biol Chem 280(39);33645-51. PMID: 16043486

Fujiwara10: Fujiwara K, Maita N, Hosaka H, Okamura-Ikeda K, Nakagawa A, Taniguchi H (2010). "Global conformational change associated with the two-step reaction catalyzed by Escherichia coli lipoate-protein ligase A." J Biol Chem 285(13);9971-80. PMID: 20089862

GOA00: GOA (2000). "Gene Ontology annotation based on Swiss-Prot keyword mapping."

GOA01a: GOA, DDB, FB, MGI, ZFIN (2001). "Gene Ontology annotation through association of InterPro records with GO terms."

GOA06: GOA, SIB (2006). "Electronic Gene Ontology annotations created by transferring manual GO annotations between orthologous microbial proteins."

GOA07: GOA, UniProt (2007). "Gene Ontology annotation based on Swiss-Prot Subcellular Location vocabulary mapping."

Green95: Green DE, Morris TW, Green J, Cronan JE, Guest JR (1995). "Purification and properties of the lipoate protein ligase of Escherichia coli." Biochem J 309 ( Pt 3);853-62. PMID: 7639702

Hassan11: Hassan BH, Cronan JE (2011). "Protein-protein interactions in assembly of lipoic acid on the 2-oxoacid dehydrogenases of aerobic metabolism." J Biol Chem 286(10);8263-76. PMID: 21209092

Hermes09: Hermes FA, Cronan JE (2009). "Scavenging of cytosolic octanoic acid by mutant LplA lipoate ligases allows growth of Escherichia coli strains lacking the LipB octanoyltransferase of lipoic acid synthesis." J Bacteriol 191(22);6796-803. PMID: 19684135

Hermes14: Hermes FA, Cronan JE (2014). "An NAD synthetic reaction bypasses the lipoate requirement for aerobic growth of Escherichia coli strains blocked in succinate catabolism." Mol Microbiol. PMID: 25303731

Ishihama08: Ishihama Y, Schmidt T, Rappsilber J, Mann M, Hartl FU, Kerner MJ, Frishman D (2008). "Protein abundance profiling of the Escherichia coli cytosol." BMC Genomics 9;102. PMID: 18304323

Jordan03: Jordan SW, Cronan JE (2003). "The Escherichia coli lipB gene encodes lipoyl (octanoyl)-acyl carrier protein:protein transferase." J Bacteriol 185(5);1582-9. PMID: 12591875

Kim05: Kim DJ, Kim KH, Lee HH, Lee SJ, Ha JY, Yoon HJ, Suh SW (2005). "Crystal structure of lipoate-protein ligase A bound with the activated intermediate: insights into interaction with lipoyl domains." J Biol Chem 280(45);38081-9. PMID: 16141198

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

Liu14: Liu DS, Nivon LG, Richter F, Goldman PJ, Deerinck TJ, Yao JZ, Richardson D, Phipps WS, Ye AZ, Ellisman MH, Drennan CL, Baker D, Ting AY (2014). "Computational design of a red fluorophore ligase for site-specific protein labeling in living cells." Proc Natl Acad Sci U S A 111(43);E4551-9. PMID: 25313043

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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
Page generated by SRI International Pathway Tools version 19.0 on Mon May 25, 2015, BIOCYC14B.