2.0 2012-05-31 10:23:43 -0600 2015-09-13 12:56:06 -0600 ECMDB00210 M2MDB000085 Pantothenic acid Pantothenic acid, also called vitamin B5, is a water-soluble vitamin required to sustain life. Pantothenic acid is needed to form coenzyme-A (CoA), and is thus critical in the metabolism and synthesis of carbohydrates, proteins, and fats. Its name is derived from the Greek pantothen meaning "from everywhere" and small quantities of pantothenic acid are found in nearly every food, with high amounts in whole grain cereals, legumes, eggs, meat, and royal jelly. (+)-Pantothenate (+)-Pantothenic acid (<i>R</i>)-pantothenic acid (D)-(+)-Pantothenate (D)-(+)-Pantothenic acid (R)-pantothenate (R)-pantothenic acid Chick antidermatitis factor D(+)-N-(2,4-Dihydroxy-3,3-dimethylbutyryl)-b-alanine D(+)-N-(2,4-Dihydroxy-3,3-dimethylbutyryl)-beta-alanine D(+)-N-(2,4-Dihydroxy-3,3-dimethylbutyryl)-β-alanine D-Pantothenate D-Pantothenic acid Delta-Pantothenate Delta-Pantothenic acid Pantothenate Vitamin B5 Vitamin B<SUB>5</SUB> δ-Pantothenate δ-Pantothenic acid C9H17NO5 219.235 219.110672659 3-[(2R)-2,4-dihydroxy-3,3-dimethylbutanamido]propanoic acid (+)-pantothenic acid 79-83-4 CC(C)(CO)C(O)C(=O)NCCC(O)=O InChI=1S/C9H17NO5/c1-9(2,5-11)7(14)8(15)10-4-3-6(12)13/h7,11,14H,3-5H2,1-2H3,(H,10,15)(H,12,13) GHOKWGTUZJEAQD-UHFFFAOYSA-N Solid Cytosol Extra-organism Periplasm logp -1.12 ALOGPS logs -0.56 ALOGPS solubility 6.05e+01 g/l ALOGPS melting_point < 25 oC logp -1.4 ChemAxon pka_strongest_acidic 4.35 ChemAxon pka_strongest_basic -2.8 ChemAxon iupac 3-[(2R)-2,4-dihydroxy-3,3-dimethylbutanamido]propanoic acid ChemAxon average_mass 219.235 ChemAxon mono_mass 219.110672659 ChemAxon smiles CC(C)(CO)C(O)C(=O)NCCC(O)=O ChemAxon formula C9H17NO5 ChemAxon inchi InChI=1S/C9H17NO5/c1-9(2,5-11)7(14)8(15)10-4-3-6(12)13/h7,11,14H,3-5H2,1-2H3,(H,10,15)(H,12,13) ChemAxon inchikey GHOKWGTUZJEAQD-UHFFFAOYSA-N ChemAxon polar_surface_area 106.86 ChemAxon refractivity 51.51 ChemAxon polarizability 21.99 ChemAxon rotatable_bond_count 6 ChemAxon acceptor_count 5 ChemAxon donor_count 4 ChemAxon physiological_charge -1 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 beta-Alanine metabolism The Beta-Alanine Metabolism starts with a product of Aspartate metabolism. Aspartate is decarboxylated by aspartate 1-decarboxylase, releasing carbon dioxide and Beta-alanine. Beta alanine is then metabolized through a pantothenate synthetase resulting in Pantothenic acid undergoes phosphorylation through a ATP driven pantothenate kinase, resulting in D-4-phosphopantothenate. Pantothenate (vitamin B5) is the universal precursor for the synthesis of the 4'-phosphopantetheine moiety of coenzyme A and acyl carrier protein. Only plants and microorganismscan synthesize pantothenate de novo - animals require a dietary supplement. The enzymes of this pathway are therefore considered to be antimicrobial drug targets. PW000896 ec00410 Metabolic Metabolic pathways eco01100 phosphopantothenate biosynthesis I PANTO-PWY Specdb::CMs 1723 Specdb::CMs 1724 Specdb::CMs 2965 Specdb::CMs 30224 Specdb::CMs 30663 Specdb::CMs 32319 Specdb::CMs 49026 Specdb::CMs 146242 Specdb::CMs 1054063 Specdb::CMs 1054064 Specdb::CMs 1054066 Specdb::CMs 1054068 Specdb::CMs 1054070 Specdb::CMs 1054072 Specdb::CMs 1054073 Specdb::CMs 1054075 Specdb::CMs 1054077 Specdb::CMs 1054079 Specdb::CMs 1054081 Specdb::CMs 1054082 Specdb::CMs 1054084 Specdb::CMs 1054086 Specdb::CMs 1054088 Specdb::CMs 1054090 Specdb::CMs 1054092 Specdb::NmrOneD 4790 Specdb::NmrOneD 4791 Specdb::NmrOneD 142910 Specdb::NmrOneD 142911 Specdb::NmrOneD 142912 Specdb::NmrOneD 142913 Specdb::NmrOneD 142914 Specdb::NmrOneD 142915 Specdb::NmrOneD 142916 Specdb::NmrOneD 142917 Specdb::NmrOneD 142918 Specdb::NmrOneD 142919 Specdb::NmrOneD 142920 Specdb::NmrOneD 142921 Specdb::NmrOneD 142922 Specdb::NmrOneD 142923 Specdb::NmrOneD 142924 Specdb::NmrOneD 142925 Specdb::NmrOneD 142926 Specdb::NmrOneD 142927 Specdb::NmrOneD 142928 Specdb::NmrOneD 142929 Specdb::MsMs 92793 Specdb::MsMs 92794 Specdb::MsMs 92795 Specdb::MsMs 156474 Specdb::MsMs 156475 Specdb::MsMs 156476 Specdb::MsMs 438264 Specdb::MsMs 438265 Specdb::MsMs 438266 Specdb::MsMs 438267 Specdb::MsMs 438268 Specdb::MsMs 438692 Specdb::MsMs 439173 Specdb::MsMs 439243 Specdb::MsMs 440107 Specdb::MsMs 446714 Specdb::MsMs 446715 Specdb::MsMs 446716 Specdb::MsMs 446717 Specdb::MsMs 446718 Specdb::MsMs 447270 Specdb::MsMs 447936 Specdb::MsMs 447937 Specdb::MsMs 448120 Specdb::MsMs 448179 Specdb::NmrTwoD 1999 Specdb::NmrTwoD 2000 HMDB00210 6613 963 C00864 16454 PANTOTHENATE Pantothenic acid 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 Sreekumar A, Poisson LM, Rajendiran TM, Khan AP, Cao Q, Yu J, Laxman B, Mehra R, Lonigro RJ, Li Y, Nyati MK, Ahsan A, Kalyana-Sundaram S, Han B, Cao X, Byun J, Omenn GS, Ghosh D, Pennathur S, Alexander DC, Berger A, Shuster JR, Wei JT, Varambally S, Beecher C, Chinnaiyan AM: Metabolomic profiles delineate potential role for sarcosine in prostate cancer progression. Nature. 2009 Feb 12;457(7231):910-4. 19212411 Shoemaker JD, Elliott WH: Automated screening of urine samples for carbohydrates, organic and amino acids after treatment with urease. J Chromatogr. 1991 Jan 2;562(1-2):125-38. 2026685 Loftus EV Jr, Tremaine WJ, Nelson RA, Shoemaker JD, Sandborn WJ, Phillips SF, Hasan Y: Dexpanthenol enemas in ulcerative colitis: a pilot study. Mayo Clin Proc. 1997 Jul;72(7):616-20. 9212762 Fry PC, Fox HM, Tao HG: Metabolic response to a pantothenic acid deficient diet in humans. J Nutr Sci Vitaminol (Tokyo). 1976;22(4):339-46. 1011047 Roth-Maier DA, Wauer A, Stangl GI, Kirchgessner M: Precaecal digestibility of niacin and pantothenic acid from different foods. Int J Vitam Nutr Res. 2000 Jan;70(1):8-13. 10683755 Preibisz J, Chlewicka I: [Digitalis treatment in acute myocardial infarct. Determination of serum drug levels] Pol Arch Med Wewn. 1977 Dec;58(6):585-91. 600836 Guilarte TR: A radiometric microbiological assay for pantothenic acid in biological fluids. Anal Biochem. 1989 Apr;178(1):63-6. 2499220 Srinivasan V, Christensen N, Wyse BW, Hansen RG: Pantothenic acid nutritional status in the elderly--institutionalized and noninstitutionalized. Am J Clin Nutr. 1981 Sep;34(9):1736-42. 7025609 Eissenstat BR, Wyse BW, Hansen RG: Pantothenic acid status of adolescents. Am J Clin Nutr. 1986 Dec;44(6):931-7. 3788840 Dastur DK, Santhadevi N, Quadros EV, Avari FC, Wadia NH, Desai MN, Bharucha EP: The B-vitamins in malnutrition with alcoholism. A model of intervitamin relationships. Br J Nutr. 1976 Sep;36(2):143-59. 182198 Kataoka, Michihiko; Shimizu, Sakayu; Doi, Yukiko; Yamada, Hideaki. Stereospecific reduction of ethyl 2'-ketopantothenate to ethyl D-(+)-pantothenate with microbial cells as a catalyst. Applied and Environmental Microbiology (1990), 56(11), 3595-7. http://hmdb.ca/system/metabolites/msds/000/000/148/original/HMDB00210.pdf?1358462271 Pantothenate kinase P0A6I3 COAA_ECOLI coaA http://ecmdb.ca/proteins/P0A6I3.xml Pantothenate synthetase P31663 PANC_ECOLI panC http://ecmdb.ca/proteins/P31663.xml Sodium/pantothenate symporter P16256 PANF_ECOLI panF http://ecmdb.ca/proteins/P16256.xml Outer membrane protein N P77747 OMPN_ECOLI ompN http://ecmdb.ca/proteins/P77747.xml Outer membrane pore protein E P02932 PHOE_ECOLI phoE http://ecmdb.ca/proteins/P02932.xml Outer membrane protein F P02931 OMPF_ECOLI ompF http://ecmdb.ca/proteins/P02931.xml Outer membrane protein C P06996 OMPC_ECOLI ompC http://ecmdb.ca/proteins/P06996.xml beta-Alanine + Adenosine triphosphate + (R)-Pantoate <> Adenosine monophosphate + Hydrogen ion + Pantothenic acid + Pyrophosphate R02473 PANTOATE-BETA-ALANINE-LIG-RXN Adenosine triphosphate + Pantothenic acid <> D-4'-Phosphopantothenate + ADP + Hydrogen ion R03018 PANTOTHENATE-KIN-RXN Adenosine triphosphate + (R)-Pantoate + beta-Alanine <> Adenosine monophosphate + Pyrophosphate + Pantothenic acid R02473 PANTOATE-BETA-ALANINE-LIG-RXN Adenosine triphosphate + Pantothenic acid <> ADP + D-4'-Phosphopantothenate R03018 PANTOTHENATE-KIN-RXN beta-Alanine + (R)-Pantoate + Adenosine triphosphate > Hydrogen ion + Pantothenic acid + Pyrophosphate + Adenosine monophosphate PANTOATE-BETA-ALANINE-LIG-RXN Pantothenic acid + Adenosine triphosphate > Hydrogen ion + D-4'-Phosphopantothenate + ADP PANTOTHENATE-KIN-RXN Pantetheine + Water + Pantetheine > Pantothenic acid + Cysteamine + Pantothenic acid PW_R002989 Pantothenic acid + Adenosine triphosphate + Pantothenic acid > D-4'-Phosphopantothenate + Adenosine diphosphate + D-4'-Phosphopantothenate + ADP PW_R002990 beta-Alanine + Adenosine triphosphate + (R)-pantoate + (R)-Pantoate > Adenosine monophosphate + Pyrophosphate + Hydrogen ion + Pantothenic acid + Pantothenic acid PW_R003001 Pantothenic acid + Adenosine triphosphate + Pantothenic acid > Adenosine diphosphate + Hydrogen ion + D-4'-Phosphopantothenate + ADP + D-4'-Phosphopantothenate PW_R003002 beta-Alanine + Adenosine triphosphate + (R)-Pantoate <> Adenosine monophosphate + Hydrogen ion + Pantothenic acid + Pyrophosphate beta-Alanine + Adenosine triphosphate + (R)-Pantoate <> Adenosine monophosphate + Hydrogen ion + Pantothenic acid + Pyrophosphate