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MetaCyc Pathway: pantothenate and coenzyme A biosynthesis I

Pathway diagram: pantothenate and coenzyme A biosynthesis I

If an enzyme name is shown in bold, there is experimental evidence for this enzymatic activity.

Superclasses: BiosynthesisCofactors, Prosthetic Groups, Electron Carriers BiosynthesisCoenzyme A Biosynthesis
BiosynthesisCofactors, Prosthetic Groups, Electron Carriers BiosynthesisVitamins Biosynthesis

Some taxa known to possess this pathway include : Escherichia coli K-12 substr. MG1655

Expected Taxonomic Range: Bacteria

General Background

Coenzyme A (CoA) is a cofactor of ubiquitous occurrence in plants, bacteria, and animals needed in a large number of enzymatic reactions central to intermediary metabolism, including the oxidation of fatty acids, carbohydrates, and amino acids. Coenzyme A is the common acyl carrier in prokaryotic and eukaryotic cells required for a multitude of reactions for both biosynthetic and degradative pathways amongst others forming derivatives that are key intermediates in energy metabolism [Rubio06].

The biosynthesis of CoA is of equal importance with regard to its recognition as a target for antibacterial drug discovery and to the association of human neurodegenerative disorder with mutations in EC, pantothenate kinase [Leonardi05].

About This Pathway

The CoA biosynthesis precursor 3-methyl-2-oxobutanoate is an intermediate in the synthesis of L-valine (see L-valine biosynthesis). This compound is converted in two steps to (R)-pantoate, as shown in phosphopantothenate biosynthesis I. The latter is converted into (R)-4'-phosphopantothenate is two steps, involving a β-alanine ligase and a kinase. In most organsims the ligase acts before the kinase ( EC, pantoate—β-alanine ligase (AMP-forming) followed by EC, pantothenate kinase, as described in phosphopantothenate biosynthesis I and phosphopantothenate biosynthesis II. However, in archaea the order is reversed, and EC, pantoate kinase acts before EC, 4-phosphopantoate—β-alanine ligase, as described in phosphopantothenate biosynthesis III.

The kinases are feedback inhibited by CoA itself, accounting for the primary regulatory mechanism of CoA biosynthesis. The addition of L-cysteine to (R)-4'-phosphopantothenate, resulting in the formation of R-4'-phosphopantothenoyl-L-cysteine (PPC), is followed by decarboxylation of PPC to 4'-phosphopantetheine. The ultimate reaction is catalyzed by EC, dephospho-CoA kinase, which converts 4'-phosphopantetheine to CoA. All enzymes of this pathway are essential for growth.

The reactions in the biosynthetic route towards CoA are identical in most organisms, although there are differences in the functionality of the involved enzymes. In plants every step is catalyzed by single monofunctional enzymes, whereas in bacteria and mammals bifunctional enzymes are often employed [Rubio06].

Subpathways: coenzyme A biosynthesis I, phosphopantothenate biosynthesis I, β-alanine biosynthesis III

Variants: coenzyme A biosynthesis II (mammalian), pantothenate and coenzyme A biosynthesis II (plants), pantothenate and coenzyme A biosynthesis III

Unification Links: EcoCyc:PANTOSYN-PWY

Created 07-Oct-2003 by Arnaud M, SRI International


Leonardi05: Leonardi R, Zhang YM, Rock CO, Jackowski S (2005). "Coenzyme A: back in action." Prog Lipid Res 44(2-3);125-53. PMID: 15893380

Rubio06: Rubio S, Larson TR, Gonzalez-Guzman M, Alejandro S, Graham IA, Serrano R, Rodriguez PL (2006). "An Arabidopsis mutant impaired in coenzyme A biosynthesis is sugar dependent for seedling establishment." Plant Physiol 140(3);830-43. PMID: 16415216

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

Albert98: Albert A, Dhanaraj V, Genschel U, Khan G, Ramjee MK, Pulido R, Sibanda BL, von Delft F, Witty M, Blundell TL, Smith AG, Abell C (1998). "Crystal structure of aspartate decarboxylase at 2.2 A resolution provides evidence for an ester in protein self-processing." Nat Struct Biol 5(4);289-93. PMID: 9546220

Arino02: Arino J (2002). "Novel protein phosphatases in yeast." Eur J Biochem 269(4);1072-7. PMID: 11856338

Badger05: Badger J, Sauder JM, Adams JM, Antonysamy S, Bain K, Bergseid MG, Buchanan SG, Buchanan MD, Batiyenko Y, Christopher JA, Emtage S, Eroshkina A, Feil I, Furlong EB, Gajiwala KS, Gao X, He D, Hendle J, Huber A, Hoda K, Kearins P, Kissinger C, Laubert B, Lewis HA, Lin J, Loomis K, Lorimer D, Louie G, Maletic M, Marsh CD, Miller I, Molinari J, Muller-Dieckmann HJ, Newman JM, Noland BW, Pagarigan B, Park F, Peat TS, Post KW, Radojicic S, Ramos A, Romero R, Rutter ME, Sanderson WE, Schwinn KD, Tresser J, Winhoven J, Wright TA, Wu L, Xu J, Harris TJ (2005). "Structural analysis of a set of proteins resulting from a bacterial genomics project." Proteins 60(4);787-96. PMID: 16021622

Begley01a: Begley TP, Kinsland C, Strauss E (2001). "The biosynthesis of coenzyme A in bacteria." Vitam Horm 61;157-71. PMID: 11153265

BRENDA14: BRENDA team (2014). Imported from BRENDA version existing on Aug 2014.

Butland05: Butland G, Peregrin-Alvarez JM, Li J, Yang W, Yang X, Canadien V, Starostine A, Richards D, Beattie B, Krogan N, Davey M, Parkinson J, Greenblatt J, Emili A (2005). "Interaction network containing conserved and essential protein complexes in Escherichia coli." Nature 433(7025);531-7. PMID: 15690043

Chakrabarti10: Chakrabarti KS, Thakur KG, Gopal B, Sarma SP (2010). "X-ray crystallographic and NMR studies of pantothenate synthetase provide insights into the mechanism of homotropic inhibition by pantoate." FEBS J 277(3);697-712. PMID: 20059543

Chetnani09: Chetnani B, Das S, Kumar P, Surolia A, Vijayan M (2009). "Mycobacterium tuberculosis pantothenate kinase: possible changes in location of ligands during enzyme action." Acta Crystallogr D Biol Crystallogr 65(Pt 4);312-25. PMID: 19307712

Chunduru89: Chunduru SK, Mrachko GT, Calvo KC (1989). "Mechanism of ketol acid reductoisomerase--steady-state analysis and metal ion requirement." Biochemistry 28(2);486-93. PMID: 2653423

Ciulli06: Ciulli A, Williams G, Smith AG, Blundell TL, Abell C (2006). "Probing hot spots at protein-ligand binding sites: a fragment-based approach using biophysical methods." J Med Chem 49(16);4992-5000. PMID: 16884311

Ciulli07: Ciulli A, Chirgadze DY, Smith AG, Blundell TL, Abell C (2007). "Crystal structure of Escherichia coli ketopantoate reductase in a ternary complex with NADP+ and pantoate bound: substrate recognition, conformational change, and cooperativity." J Biol Chem 282(11);8487-97. PMID: 17229734

Ciulli07a: Ciulli A, Lobley CM, Tuck KL, Smith AG, Blundell TL, Abell C (2007). "pH-tuneable binding of 2'-phospho-ADP-ribose to ketopantoate reductase: a structural and calorimetric study." Acta Crystallogr D Biol Crystallogr 63(Pt 2);171-8. PMID: 17242510

Clifton70: Clifton G, Bryant SR, Skinner CG (1970). "N'-(substituted) pantothenamides, antimetabolites of pantothenic acid." Arch Biochem Biophys 137(2);523-8. PMID: 4909169

Cronan80: Cronan JE (1980). "Beta-alanine synthesis in Escherichia coli." J Bacteriol 1980;141(3);1291-7. PMID: 6767707

Cronan82: Cronan JE, Littel KJ, Jackowski S (1982). "Genetic and biochemical analyses of pantothenate biosynthesis in Escherichia coli and Salmonella typhimurium." J Bacteriol 149(3);916-22. PMID: 7037743

Daugherty02: Daugherty M, Polanuyer B, Farrell M, Scholle M, Lykidis A, de Crecy-Lagard V, Osterman A (2002). "Complete reconstitution of the human coenzyme A biosynthetic pathway via comparative genomics." J Biol Chem 277(24);21431-9. PMID: 11923312

deNadal98: de Nadal E, Clotet J, Posas F, Serrano R, Gomez N, Arino J (1998). "The yeast halotolerance determinant Hal3p is an inhibitory subunit of the Ppz1p Ser/Thr protein phosphatase." Proc Natl Acad Sci U S A 95(13);7357-62. PMID: 9636153

Diaz91: Diaz E, Anton DL (1991). "Alkylation of an active-site cysteinyl residue during substrate-dependent inactivation of Escherichia coli S-adenosylmethionine decarboxylase." Biochemistry 1991;30(16);4078-81. PMID: 2018773

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

Downs94: Downs DM, Petersen L (1994). "apbA, a new genetic locus involved in thiamine biosynthesis in Salmonella typhimurium." J Bacteriol 176(16);4858-64. PMID: 7519593

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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 Pathway Tools version 19.5 (software by SRI International) on Wed May 4, 2016, biocyc13.