2.0 2012-05-31 13:51:14 -0600 2015-09-13 12:56:11 -0600 ECMDB01373 M2MDB000362 Dephospho-CoA Dephospho-CoA is a substrate for Ectonucleotide pyrophosphatase/phosphodiesterase 1, Ectonucleotide pyrophosphatase/phosphodiesterase 3 and Ectonucleotide pyrophosphatase/phosphodiesterase 2. 3'-dephospho-CoA 3'-dephospho-Coenzyme A 3'-O-Dephosphono-CoA 3'-O-Dephosphono-Coenzyme A 3-Dephospho-CoA DePCoA Dephospho-CoA Dephospho-Coenzyme A Dephosphocoenzyme a C21H35N7O13P2S 687.554 687.148877955 [({[(2R,3S,4R,5R)-5-(6-amino-9H-purin-9-yl)-3,4-dihydroxyoxolan-2-yl]methoxy}(hydroxy)phosphoryl)oxy][3-hydroxy-2,2-dimethyl-3-({2-[(2-sulfanylethyl)carbamoyl]ethyl}carbamoyl)propoxy]phosphinic acid {[(2R,3S,4R,5R)-5-(6-aminopurin-9-yl)-3,4-dihydroxyoxolan-2-yl]methoxy(hydroxy)phosphoryl}oxy(3-hydroxy-2,2-dimethyl-3-({2-[(2-sulfanylethyl)carbamoyl]ethyl}carbamoyl)propoxy)phosphinic acid 3633-59-8 CC(C)(COP(O)(=O)OP(O)(=O)OC[C@H]1O[C@H]([C@H](O)[C@@H]1O)N1C=NC2=C1N=CN=C2N)C(O)C(=O)NCCC(=O)NCCS InChI=1S/C21H35N7O13P2S/c1-21(2,16(32)19(33)24-4-3-12(29)23-5-6-44)8-39-43(36,37)41-42(34,35)38-7-11-14(30)15(31)20(40-11)28-10-27-13-17(22)25-9-26-18(13)28/h9-11,14-16,20,30-32,44H,3-8H2,1-2H3,(H,23,29)(H,24,33)(H,34,35)(H,36,37)(H2,22,25,26)/t11-,14-,15-,16?,20-/m1/s1 KDTSHFARGAKYJN-DRCCLKDXSA-N Solid Cytosol logp -0.98 ALOGPS logs -2.43 ALOGPS solubility 2.56e+00 g/l ALOGPS logp -5.9 ChemAxon pka_strongest_acidic 1.86 ChemAxon pka_strongest_basic 5 ChemAxon iupac [({[(2R,3S,4R,5R)-5-(6-amino-9H-purin-9-yl)-3,4-dihydroxyoxolan-2-yl]methoxy}(hydroxy)phosphoryl)oxy][3-hydroxy-2,2-dimethyl-3-({2-[(2-sulfanylethyl)carbamoyl]ethyl}carbamoyl)propoxy]phosphinic acid ChemAxon average_mass 687.554 ChemAxon mono_mass 687.148877955 ChemAxon smiles CC(C)(COP(O)(=O)OP(O)(=O)OC[C@H]1O[C@H]([C@H](O)[C@@H]1O)N1C=NC2=C1N=CN=C2N)C(O)C(=O)NCCC(=O)NCCS ChemAxon formula C21H35N7O13P2S ChemAxon inchi InChI=1S/C21H35N7O13P2S/c1-21(2,16(32)19(33)24-4-3-12(29)23-5-6-44)8-39-43(36,37)41-42(34,35)38-7-11-14(30)15(31)20(40-11)28-10-27-13-17(22)25-9-26-18(13)28/h9-11,14-16,20,30-32,44H,3-8H2,1-2H3,(H,23,29)(H,24,33)(H,34,35)(H,36,37)(H2,22,25,26)/t11-,14-,15-,16?,20-/m1/s1 ChemAxon inchikey KDTSHFARGAKYJN-DRCCLKDXSA-N ChemAxon polar_surface_area 300.03 ChemAxon refractivity 151.87 ChemAxon polarizability 62.51 ChemAxon rotatable_bond_count 16 ChemAxon acceptor_count 14 ChemAxon donor_count 9 ChemAxon physiological_charge -2 ChemAxon formal_charge 0 ChemAxon Pantothenate and CoA biosynthesis The CoA biosynthesis requires compounds from two other pathways: aspartate metabolism and valine biosynthesis. It requires a Beta-Alanine and R-pantoate. The compound (R)-pantoate is generated in two reactions, as shown by the interaction of alpha-ketoisovaleric acid, 5,10 methylene-THF and water through a 3-methyl-2-oxobutanoate hydroxymethyltransferase resulting in a tetrahydrofolic acid and a 2-dehydropantoate. This compound interacts with hydrogen through a NADPH driven acetohydroxy acid isomeroreductase resulting in the release of NADP and R-pantoate. On the other hand L-aspartic acid interacts with a hydrogen ion and gets decarboxylated through an Aspartate 1- decarboxylase resulting in a carbon dioxide and a Beta-alanine. Beta-alanine and R-pantoate interact with an ATP driven pantothenate synthetase resulting in pyrophosphate, AMP, hydrogen ion and pantothenic acid. Pantothenic acid is phosphorylated through a ATP-driven pantothenate kinase resulting in a ADP, a hydrogen ion and D-4'-Phosphopantothenate. This compound interacts with a CTP and a L-cysteine resulting in a fused 4'-phosphopantothenoylcysteine decarboxylase and phosphopantothenoylcysteine synthetase resulting in a hydrogen ion, a pyrophosphate, a CMP and 4-phosphopantothenoylcysteine. The latter compound interacts with a hydrogen ion through a fused 4'-phosphopantothenoylcysteine decarboxylase and phosphopantothenoylcysteine synthetase resulting in a carbon dioxide release and a 4-phosphopantetheine. This compound interacts with an ATP, hydrogen ion and an phosphopantetheine adenylyltransferase resulting in a release of pyrophosphate, and dephospho-CoA. Dephospho-CoA reacts with an ATP driven dephospho-CoA kinase resulting in a ADP , a hydrogen ion and a Coenzyme A. . 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 6.3.2.1, pantoate—β-alanine ligase (AMP-forming) followed by EC 2.7.1.33, pantothenate kinase, as described in phosphopantothenate biosynthesis I and phosphopantothenate biosynthesis II. However, in archaea the order is reversed, and EC 2.7.1.169, pantoate kinase acts before EC 6.3.2.36, 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 2.7.1.24, 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]. PW000828 ec00770 Metabolic Two-component system ec02020 Metabolic pathways eco01100 Citrate lyase activation The citrate lyase activation starts with a 3-dephospho-CoA reacting with ATP and a hydrogen ion through a triphosphoribosyl-dephospho-CoA synthase resulting in a adenine and a 2'-(5'-triphospho-alpha-D-ribosyl)-3'-dephospho-CoA. The latter compound in turn reacts with with a citrate lyase acyl-carrier protein through a apo-citrate lyase phosphoribosyl-dephospho-CoA transferase resulting in the release of a pyrophosphate and a hydrogen ion and a holo citrate lyase acyl-carrier protein.This protein complex can either react with a hydrogen ion and a acetate resulting in the release of a water and an acetyl-holo citrate lyase acyl-carrier protein. The holo acyl-carrier protein creacts with an ATP and an acetate through a citrate lyase synthase resulting in the release of an AMP, a pyrophosphate and an acetyl-holo citrate lyase acyl-ccarrier protein. The holo citrate lyase acyl-carrier protein can also interact with an S-acetyl phosphopantethiene resulting in the release of a 4-phosphopantethiene and an acetyl-holo citrate lyase acyl-carrier protein. PW002075 Metabolic 2'-(5'-phosphoribosyl)-3'-dephospho-CoA biosynthesis I (citrate lyase) P2-PWY coenzyme A biosynthesis COA-PWY Specdb::CMs 22053 Specdb::NmrOneD 273418 Specdb::NmrOneD 273419 Specdb::NmrOneD 273420 Specdb::NmrOneD 273421 Specdb::NmrOneD 273422 Specdb::NmrOneD 273423 Specdb::NmrOneD 273424 Specdb::NmrOneD 273425 Specdb::NmrOneD 273426 Specdb::NmrOneD 273427 Specdb::NmrOneD 273428 Specdb::NmrOneD 273429 Specdb::NmrOneD 273430 Specdb::NmrOneD 273431 Specdb::NmrOneD 273432 Specdb::NmrOneD 273433 Specdb::NmrOneD 273434 Specdb::NmrOneD 273435 Specdb::NmrOneD 273436 Specdb::NmrOneD 273437 Specdb::MsMs 23369 Specdb::MsMs 23370 Specdb::MsMs 23371 Specdb::MsMs 30167 Specdb::MsMs 30168 Specdb::MsMs 30169 HMDB01373 444485 388463 C00882 15468 DEPHOSPHO-COA Keseler, I. M., Collado-Vides, J., Santos-Zavaleta, A., Peralta-Gil, M., Gama-Castro, S., Muniz-Rascado, L., Bonavides-Martinez, C., Paley, S., Krummenacker, M., Altman, T., Kaipa, P., Spaulding, A., Pacheco, J., Latendresse, M., Fulcher, C., Sarker, M., Shearer, A. G., Mackie, A., Paulsen, I., Gunsalus, R. P., Karp, P. D. (2011). "EcoCyc: a comprehensive database of Escherichia coli biology." Nucleic Acids Res 39:D583-D590. 21097882 Kanehisa, M., Goto, S., Sato, Y., Furumichi, M., Tanabe, M. (2012). "KEGG for integration and interpretation of large-scale molecular data sets." Nucleic Acids Res 40:D109-D114. 22080510 van der Werf, M. J., Overkamp, K. M., Muilwijk, B., Coulier, L., Hankemeier, T. (2007). "Microbial metabolomics: toward a platform with full metabolome coverage." Anal Biochem 370:17-25. 17765195 Winder, C. L., Dunn, W. B., Schuler, S., Broadhurst, D., Jarvis, R., Stephens, G. M., Goodacre, R. (2008). "Global metabolic profiling of Escherichia coli cultures: an evaluation of methods for quenching and extraction of intracellular metabolites." Anal Chem 80:2939-2948. 18331064 Haugen HF, Skrede S: Nucleotide pyrophosphatase and phosphodiesterase I. Demonstration of activity in normal serum, and an increase in cholestatic liver disease. Scand J Gastroenterol. 1976;11(2):121-7. 4880 http://hmdb.ca/system/metabolites/msds/000/001/235/original/HMDB01373.pdf?1358461914 Phosphopantetheine adenylyltransferase P0A6I6 COAD_ECOLI coaD http://ecmdb.ca/proteins/P0A6I6.xml Dephospho-CoA kinase P0A6I9 COAE_ECOLI coaE http://ecmdb.ca/proteins/P0A6I9.xml 2-(5''-triphosphoribosyl)-3'-dephosphocoenzyme-A synthase P77231 CITG_ECOLI citG http://ecmdb.ca/proteins/P77231.xml Adenosine triphosphate + Dephospho-CoA <> ADP + Coenzyme A + Hydrogen ion R00130 DEPHOSPHOCOAKIN-RXN Adenosine triphosphate + Dephospho-CoA > 2'-(5-Triphosphoribosyl)-3'-dephospho-CoA + Adenine 2.7.8.25-RXN Adenosine triphosphate + Hydrogen ion + Pantetheine 4'-phosphate <> Dephospho-CoA + Pyrophosphate R03035 PANTEPADENYLYLTRAN-RXN Adenosine triphosphate + Dephospho-CoA <> ADP + Coenzyme A R00130 Adenosine triphosphate + Pantetheine 4'-phosphate <> Pyrophosphate + Dephospho-CoA R03035 Hydrogen ion + Dephospho-CoA + Adenosine triphosphate > 2'-(5-Triphosphoribosyl)-3'-dephospho-CoA + Adenine 2.7.8.25-RXN Dephospho-CoA + Adenosine triphosphate > Hydrogen ion + Coenzyme A + ADP DEPHOSPHOCOAKIN-RXN Adenosine triphosphate + Dephospho-CoA <> 2'-(5-Triphosphoribosyl)-3'-dephospho-CoA + Adenine R09675 Pantetheine 4'-phosphate + Adenosine triphosphate + pantotheine 4'-phosphate > Dephospho-CoA + Pyrophosphate PW_R002995 Adenosine triphosphate + Dephospho-CoA > Adenosine diphosphate + Coenzyme A + ADP PW_R002996 Dephospho-CoA + Water <> Pantetheine 4'-phosphate + Adenosine monophosphate + pantotheine 4'-phosphate PW_R002997 4'-phosphopantetheine + Adenosine triphosphate + Hydrogen ion + 4'-phosphopantetheine > Pyrophosphate + Dephospho-CoA PW_R003004 Dephospho-CoA + Adenosine triphosphate > Hydrogen ion + Adenosine diphosphate + Coenzyme A + ADP PW_R003006 Adenosine triphosphate + Hydrogen ion + Pantetheine 4'-phosphate <> Dephospho-CoA + Pyrophosphate Adenosine triphosphate + Dephospho-CoA <> ADP + Coenzyme A + Hydrogen ion Adenosine triphosphate + Hydrogen ion + Pantetheine 4'-phosphate <> Dephospho-CoA + Pyrophosphate