2.0 2012-05-31 13:45:29 -0600 2015-06-03 15:53:45 -0600 ECMDB01117 M2MDB000259 4-Phosphopantothenoylcysteine 4-Phosphopantothenoylcysteine (PPC) is an intermediate in the biosynthetic machinery (pathway) that converts pantothenate (vitamin B5) into coenzyme A (CoA). The enzyme Phosphopantothenoylcysteine decarboxylase catalyzes the decarboxylation of PPC to 4'-phosphopantetheine. Coenzyme A is the principal acyl carrier and is required for many synthetic and degradative reactions in intermediary metabolism, and is an essential cofactor in all living systems. (PMID: 15450493, 16371361, 14501115) (R)-4'-phospho-N-pantothenoyl-L-cysteine (R)-4'-phosphopantothenoyl-L-cysteine (R)-N-[N-[2-hydroxy-3,3-dimethyl-1-oxo-4-(phosphonooxy)butyl]-b-alanyl]-L-Cysteine (R)-N-[N-[2-hydroxy-3,3-dimethyl-1-oxo-4-(phosphonooxy)butyl]-beta-alanyl]-L-Cysteine (R)-N-[N-[2-Hydroxy-3,3-dimethyl-1-oxo-4-(phosphonooxy)butyl]-β-alanyl]-L-cysteine 4'-P-N-Pantothenoylcysteine 4'-Phospho-N-pantothenoylcysteine 4'-Phosphopantothenoyl-L-cysteine 4'-Phosphopantothenoylcysteine 4'PPC 4-P-N-Pantothenoylcysteine N-((R)-4'-Phosphopantothenoyl)-L-cysteine N-((R)-4-Phosphopantothenoyl)-L-cysteine N-[(R)-4'-Phosphopantothenoyl]-L-cysteine Pantothenoylcysteine 4'-phosphate Pantothenoylcysteine 4'-phosphoric acid PPC C12H23N2O9PS 402.358 402.086187546 (2R)-2-{3-[(2R)-2-hydroxy-3-methyl-3-[(phosphonooxy)methyl]butanamido]propanamido}-3-sulfanylpropanoic acid (2R)-2-{3-[(2R)-2-hydroxy-3-methyl-3-[(phosphonooxy)methyl]butanamido]propanamido}-3-sulfanylpropanoic acid 7196-09-0 CC(C)(COP(O)(O)=O)[C@@H](O)C(=O)NCCC(=O)N[C@@H](CS)C(O)=O InChI=1S/C12H23N2O9PS/c1-12(2,6-23-24(20,21)22)9(16)10(17)13-4-3-8(15)14-7(5-25)11(18)19/h7,9,16,25H,3-6H2,1-2H3,(H,13,17)(H,14,15)(H,18,19)(H2,20,21,22)/t7-,9-/m0/s1 XQYALQVLCNHCFT-CBAPKCEASA-N Solid Cytosol logp -0.88 ALOGPS logs -3.08 ALOGPS solubility 3.36e-01 g/l ALOGPS logp -2 ChemAxon pka_strongest_acidic 1.78 ChemAxon pka_strongest_basic -3.8 ChemAxon iupac (2R)-2-{3-[(2R)-2-hydroxy-3-methyl-3-[(phosphonooxy)methyl]butanamido]propanamido}-3-sulfanylpropanoic acid ChemAxon average_mass 402.358 ChemAxon mono_mass 402.086187546 ChemAxon smiles CC(C)(COP(O)(O)=O)[C@@H](O)C(=O)NCCC(=O)N[C@@H](CS)C(O)=O ChemAxon formula C12H23N2O9PS ChemAxon inchi InChI=1S/C12H23N2O9PS/c1-12(2,6-23-24(20,21)22)9(16)10(17)13-4-3-8(15)14-7(5-25)11(18)19/h7,9,16,25H,3-6H2,1-2H3,(H,13,17)(H,14,15)(H,18,19)(H2,20,21,22)/t7-,9-/m0/s1 ChemAxon inchikey XQYALQVLCNHCFT-CBAPKCEASA-N ChemAxon polar_surface_area 182.49 ChemAxon refractivity 87.41 ChemAxon polarizability 36.25 ChemAxon rotatable_bond_count 11 ChemAxon acceptor_count 8 ChemAxon donor_count 7 ChemAxon physiological_charge -3 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 Metabolic pathways eco01100 coenzyme A biosynthesis COA-PWY Specdb::CMs 3399 Specdb::CMs 37931 Specdb::CMs 157264 Specdb::NmrOneD 21242 Specdb::NmrOneD 21243 Specdb::NmrOneD 21244 Specdb::NmrOneD 21245 Specdb::NmrOneD 21246 Specdb::NmrOneD 21247 Specdb::NmrOneD 21248 Specdb::NmrOneD 21249 Specdb::NmrOneD 21250 Specdb::NmrOneD 21251 Specdb::NmrOneD 21252 Specdb::NmrOneD 21253 Specdb::NmrOneD 21254 Specdb::NmrOneD 21255 Specdb::NmrOneD 21256 Specdb::NmrOneD 21257 Specdb::NmrOneD 21258 Specdb::NmrOneD 21259 Specdb::NmrOneD 21260 Specdb::NmrOneD 21261 Specdb::MsMs 23054 Specdb::MsMs 23055 Specdb::MsMs 23056 Specdb::MsMs 29852 Specdb::MsMs 29853 Specdb::MsMs 29854 Specdb::MsMs 2842824 Specdb::MsMs 2842825 Specdb::MsMs 2842826 Specdb::MsMs 2866854 Specdb::MsMs 2866855 Specdb::MsMs 2866856 HMDB01117 440304 389278 C04352 15769 R-4-PHOSPHOPANTOTHENOYL-L-CYSTEINE 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). 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Epub 2005 Dec 21. 16371361 Pantothenate kinase P0A6I3 COAA_ECOLI coaA http://ecmdb.ca/proteins/P0A6I3.xml Coenzyme A biosynthesis bifunctional protein coaBC P0ABQ0 COABC_ECOLI coaBC http://ecmdb.ca/proteins/P0ABQ0.xml D-4'-Phosphopantothenate + Cytidine triphosphate + L-Cysteine > 4-Phosphopantothenoylcysteine + Cytidine monophosphate + Hydrogen ion + Pyrophosphate R04231 P-PANTOCYSLIG-RXN 4-Phosphopantothenoylcysteine + Hydrogen ion <> Carbon dioxide + Pantetheine 4'-phosphate + pantotheine 4'-phosphate R03269 P-PANTOCYSDECARB-RXN 4-Phosphopantothenoylcysteine <> Pantetheine 4'-phosphate + Carbon dioxide R03269 Adenosine triphosphate + D-4'-Phosphopantothenate + L-Cysteine <> Adenosine monophosphate + Pyrophosphate + 4-Phosphopantothenoylcysteine R04230 Cytidine triphosphate + D-4'-Phosphopantothenate + L-Cysteine <> Cytidine monophosphate + Pyrophosphate + 4-Phosphopantothenoylcysteine R04231 Adenosine triphosphate + D-Pantothenoyl-L-cysteine <> ADP + 4-Phosphopantothenoylcysteine R04391 Hydrogen ion + 4-Phosphopantothenoylcysteine > Pantetheine 4'-phosphate + Carbon dioxide P-PANTOCYSDECARB-RXN 4-Phosphopantothenoylcysteine > pantotheine 4'-phosphate + Carbon dioxide Cytidine triphosphate + (R)-4'-phosphopantothenate + L-Cysteine > Cytidine monophosphate + Pyrophosphate + 4-Phosphopantothenoylcysteine Adenosine triphosphate + D-Pantothenoyl-L-cysteine > Adenosine diphosphate + 4-Phosphopantothenoylcysteine + ADP PW_R002994 Cytidine triphosphate + D-4'-Phosphopantothenate + L-Cysteine + D-4'-Phosphopantothenate > Cytidine monophosphate + Pyrophosphate + 4-Phosphopantothenoylcysteine + Cytidine monophosphate PW_R002991 4-Phosphopantothenoylcysteine > Pantetheine 4'-phosphate + Carbon dioxide + pantotheine 4'-phosphate PW_R002993 D-4'-Phosphopantothenate + Cytidine triphosphate + L-Cysteine + D-4'-Phosphopantothenate > Cytidine monophosphate + Pyrophosphate + Hydrogen ion + 4-Phosphopantothenoylcysteine + Cytidine monophosphate PW_R003003 4-Phosphopantothenoylcysteine + Hydrogen ion > Carbon dioxide + 4'-phosphopantetheine + 4'-phosphopantetheine PW_R003005 D-4'-Phosphopantothenate + Cytidine triphosphate + L-Cysteine >4 4-Phosphopantothenoylcysteine + Cytidine monophosphate + Hydrogen ion + Pyrophosphate D-4'-Phosphopantothenate + Cytidine triphosphate + L-Cysteine >4 4-Phosphopantothenoylcysteine + Cytidine monophosphate + Hydrogen ion + Pyrophosphate