2.0 2012-05-31 13:51:21 -0600 2015-10-02 02:25:47 -0600 ECMDB01384 M2MDB000364 UDP-Glucuronic acid UDP-Glucuronic acid is an intermediate in polymyxin resistance in E. coli. It is a substrate for UDP-GlcA C-4"-decarboxylase (gene name: arnA) which catalyzes the chemical reaction UDP-D-glucuronate + NAD+ -> UDP-beta-L-threo-pentapyranos-4-ulose + CO2 + NADH. In UDP-alpha-D-glucuronate biosynthesis (from UDP-glucose), UDP-glucose 6-dehydrogenase converts UDP-alpha-D-glucose to UDP-Glucuronic acid (EcoCyc compound: UDP-GLUCURONATE). UDP-D-Glucuronate UDP-D-Glucuronic acid UDP-Glucuronate UDP-Glucuronic acid UDPglucuronate UDPglucuronic acid Uridine diphosphate glucuronate Uridine diphosphate glucuronic acid Uridine diphosphoric acid glucuronic acid C15H22N2O18P2 580.2853 580.034284934 (2S,3S,4S,5R,6R)-6-({[({[(2R,3S,4R,5R)-5-(2,4-dioxo-1,2,3,4-tetrahydropyrimidin-1-yl)-3,4-dihydroxyoxolan-2-yl]methoxy}(hydroxy)phosphoryl)oxy](hydroxy)phosphoryl}oxy)-3,4,5-trihydroxyoxane-2-carboxylic acid udp-α-D-glucuronic acid 2616-64-0 O[C@@H]1[C@@H](COP(O)(=O)OP(O)(=O)O[C@H]2O[C@@H]([C@@H](O)[C@H](O)[C@H]2O)C(O)=O)O[C@H]([C@@H]1O)N1C=CC(=O)NC1=O InChI=1S/C15H22N2O18P2/c18-5-1-2-17(15(26)16-5)12-9(22)6(19)4(32-12)3-31-36(27,28)35-37(29,30)34-14-10(23)7(20)8(21)11(33-14)13(24)25/h1-2,4,6-12,14,19-23H,3H2,(H,24,25)(H,27,28)(H,29,30)(H,16,18,26)/t4-,6-,7+,8+,9-,10-,11+,12-,14-/m1/s1 HDYANYHVCAPMJV-LXQIFKJMSA-N Cytosol Extra-organism Periplasm logp -1.21 ALOGPS logs -1.51 ALOGPS solubility 1.81e+01 g/l ALOGPS logp -4.7 ChemAxon pka_strongest_acidic 1.72 ChemAxon pka_strongest_basic -3.7 ChemAxon iupac (2S,3S,4S,5R,6R)-6-({[({[(2R,3S,4R,5R)-5-(2,4-dioxo-1,2,3,4-tetrahydropyrimidin-1-yl)-3,4-dihydroxyoxolan-2-yl]methoxy}(hydroxy)phosphoryl)oxy](hydroxy)phosphoryl}oxy)-3,4,5-trihydroxyoxane-2-carboxylic acid ChemAxon average_mass 580.2853 ChemAxon mono_mass 580.034284934 ChemAxon smiles O[C@@H]1[C@@H](COP(O)(=O)OP(O)(=O)O[C@H]2O[C@@H]([C@@H](O)[C@H](O)[C@H]2O)C(O)=O)O[C@H]([C@@H]1O)N1C=CC(=O)NC1=O ChemAxon formula C15H22N2O18P2 ChemAxon inchi InChI=1S/C15H22N2O18P2/c18-5-1-2-17(15(26)16-5)12-9(22)6(19)4(32-12)3-31-36(27,28)35-37(29,30)34-14-10(23)7(20)8(21)11(33-14)13(24)25/h1-2,4,6-12,14,19-23H,3H2,(H,24,25)(H,27,28)(H,29,30)(H,16,18,26)/t4-,6-,7+,8+,9-,10-,11+,12-,14-/m1/s1 ChemAxon inchikey HDYANYHVCAPMJV-LXQIFKJMSA-N ChemAxon polar_surface_area 308.61 ChemAxon refractivity 106.32 ChemAxon polarizability 45.33 ChemAxon rotatable_bond_count 9 ChemAxon acceptor_count 15 ChemAxon donor_count 9 ChemAxon physiological_charge -3 ChemAxon formal_charge 0 ChemAxon Starch and sucrose metabolism The metabolism of starch and sucrose begins with D-fructose interacting with a D-glucose in a reversible reaction through a maltodextrin glucosidase resulting in a water molecule and a sucrose. D-fructose is phosphorylated through an ATP driven fructokinase resulting in the release of an ADP, a hydrogen ion and a Beta-D-fructofuranose 6-phosphate. This compound can also be introduced into the cytoplasm through either a mannose PTS permease or a hexose-6-phosphate:phosphate antiporter. The Beta-D-fructofuranose 6-phosphate is isomerized through a phosphoglucose isomerase resulting in a Beta-D-glucose 6-phosphate. This compound can also be incorporated by glucose PTS permease or a hexose-6-phosphate:phosphate antiporter. The beta-D-glucose 6 phosphate can also be produced by a D-glucose being phosphorylated by an ATP-driven glucokinase resulting in a ADP, a hydrogen ion and a Beta-D-glucose 6 phosphate. The beta-D-glucose can produce alpha-D-glucose-1-phosphate by two methods: 1.-Beta-D-glucose is isomerized into an alpha-D-Glucose 6-phosphate and then interacts in a reversible reaction through a phosphoglucomutase-1 resulting in a alpha-D-glucose-1-phosphate. 2.-Beta-D-glucose interacts with a putative beta-phosphoglucomutase resulting in a Beta-D-glucose 1-phosphate. Beta-D-glucose 1-phosphate can be incorporated into the cytoplasm through a glucose PTS permease. This compound is then isomerized into a Alpha-D-glucose-1-phosphate The beta-D-glucose can cycle back into a D-fructose by first interacting with D-fructose in a reversible reaction through a Polypeptide: predicted glucosyltransferase resulting in the release of a phosphate and a sucrose. The sucrose then interacts in a reversible reaction with a water molecule through a maltodextrin glucosidase resulting in a D-glucose and a D-fructose. Alpha-D-glucose-1-phosphate can produce glycogen in by two different sets of reactions: 1.-Alpha-D-glucose-1-phosphate interacts with a hydrogen ion and an ATP through a glucose-1-phosphate adenylyltransferase resulting in a pyrophosphate and an ADP-glucose. The ADP-glucose then interacts with an amylose through a glycogen synthase resulting in the release of an ADP and an Amylose. The amylose then interacts with 1,4-α-glucan branching enzyme resulting in glycogen 2.- Alpha-D-glucose-1-phosphate interacts with amylose through a maltodextrin phosphorylase resulting in a phosphate and a glycogen. Alpha-D-glucose-1-phosphate can also interacts with UDP-galactose through a galactose-1-phosphate uridylyltransferase resulting in a galactose 1-phosphate and a Uridine diphosphate glucose. The UDP-glucose then interacts with an alpha-D-glucose 6-phosphate through a trehalose-6-phosphate synthase resulting in a uridine 5'-diphosphate, a hydrogen ion and a Trehalose 6- phosphate. The latter compound can also be incorporated into the cytoplasm through a trehalose PTS permease. Trehalose interacts with a water molecule through a trehalose-6-phosphate phosphatase resulting in the release of a phosphate and an alpha,alpha-trehalose.The alpha,alpha-trehalose can also be obtained from glycogen being metabolized through a glycogen debranching enzyme resulting in a the alpha, alpha-trehalose. This compound ca then be hydrated through a cytoplasmic trehalase resulting in the release of an alpha-D-glucose and a beta-d-glucose. Glycogen is then metabolized by reacting with a phosphate through a glycogen phosphorylase resulting in a alpha-D-glucose-1-phosphate and a dextrin. The dextrin is then hydrated through a glycogen phosphorylase-limit dextrin α-1,6-glucohydrolase resulting in the release of a debranched limit dextrin and a maltotetraose. This compound can also be incorporated into the cytoplasm through a maltose ABC transporter. The maltotetraose interacts with a phosphate through a maltodextrin phosphorylase releasing a alpha-D-glucose-1-phosphate and a maltotriose. The maltotriose can also be incorporated through a maltose ABC transporter. The maltotriose can then interact with water through a maltodextrin glucosidase resulting in a D-glucose and a D-maltose. D-maltose can also be incorporated through a maltose ABC transporter The D-maltose can then interact with a maltotriose through a amylomaltase resulting in a maltotetraose and a D-glucose. The D-glucose is then phosphorylated through an ATP driven glucokinase resulting in a hydrogen ion, an ADP and a Beta-D-glucose 6-phosphate PW000941 ec00500 Metabolic Ascorbate and aldarate metabolism ec00053 Amino sugar and nucleotide sugar metabolism ec00520 Pentose and glucuronate interconversions ec00040 Metabolic pathways eco01100 Amino sugar and nucleotide sugar metabolism III The synthesis of amino sugars and nucleotide sugars starts with the phosphorylation of N-Acetylmuramic acid (MurNac) through its transport from the periplasmic space to the cytoplasm. Once in the cytoplasm, MurNac and water undergo a reversible reaction through a N-acetylmuramic acid 6-phosphate etherase, producing a D-lactic acid and N-Acetyl-D-Glucosamine 6-phosphate. This latter compound can also be introduced into the cytoplasm through a phosphorylating PTS permase in the inner membrane that allows for the transport of N-Acetyl-D-glucosamine from the periplasmic space. N-Acetyl-D-Glucosamine 6-phosphate can also be obtained from chitin dependent reactions. Chitin is hydrated through a bifunctional chitinase to produce chitobiose. This in turn gets hydrated by a beta-hexosaminidase to produce N-acetyl-D-glucosamine. The latter undergoes an atp dependent phosphorylation leading to the production of N-Acetyl-D-Glucosamine 6-phosphate. N-Acetyl-D-Glucosamine 6-phosphate is then be deacetylated in order to produce Glucosamine 6-phosphate through a N-acetylglucosamine-6-phosphate deacetylase. This compound is then deaminased into Beta-D-fructofuranose 6-phosphate through a glucosamine-6-phosphate deaminase. Beta-D-fructofuranose 6-phosphate is isomerized into a beta-D-glucose 6-phosphate through a glucose-6-phosphate isomerase. The compound is then isomerized by a putative beta-phosphoglucomutase to produce a beta-D-glucose 1-phosphate. This compound enters the nucleotide sugar metabolism through uridylation resulting in a UDP-glucose. UDP-glucose is then dehydrated through a UDP-glucose 6-dehydrogenase to produce a UDP-glucuronic acid. This compound undergoes a NAD dependent reaction through a bifunctional polymyxin resistance protein to produce UDP-Beta-L-threo-pentapyranos-4-ulose. This compound then reacts with L-glutamic acid through a UDP-4-amino-4-deoxy-L-arabinose--oxoglutarate aminotransferase to produce an oxoglutaric acid and UDP-4-amino-4-deoxy-beta-L-arabinopyranose The latter compound interacts with a N10-formyl-tetrahydrofolate through a bifunctional polymyxin resistance protein ArnA, resulting in a tetrahydrofolate, a hydrogen ion and a UDP-4-deoxy-4-formamido-beta-L-arabinopyranose, which in turn reacts with a product of the methylerythritol phosphate and polysoprenoid biosynthesis pathway, di-trans,octa-cis-undecaprenyl phosphate to produce a 4-deoxy-4-formamido-alpha-L-arabinopyranosyl ditrans, octacis-undecaprenyl phosphate. Alpha-D-glucose is introduced into the cytoplasm through a glucose PTS permease, which phosphorylates the compound in order to produce an alpha-D-glucose 6-phosphate. This compound is then modified through a phosphoglucomutase 1 to yield alpha-D-glucose 1-phosphate. This compound can either be adenylated to produce ADP-glucose or uridylylated to produce galactose 1-phosphate through glucose-1-phosphate adenyllyltransferase and galactose-1-phosphate uridylyltransferase respectively. PW000895 Metabolic colanic acid building blocks biosynthesis The colonic acid building blocks biosynthesis starts with a Beta-D-Glucose undergoing a transport reaction mediated by a glucose PTS permease. The permease phosphorylates the Beta-D-Glucose, producing a Beta-D-Glucose 6-phosphate. This compound can either change to an Alpha-D-Glucose 6-phosphate spontaneously or into a fructose 6-phosphate through a glucose-6-phosphate isomerase. The latter compound can also be present in E.coli through the interaction of D-fructose and a mannose PTS permease which phosphorylate the D-fructose. Fructose 6-phosphate interacts in a reversible reaction with mannose-6-phosphate isomerase in order to produce a Alpha-D-mannose 6-phosphate. This compound can also be present in E.coli through the interaction of Alpha-D-mannose and a mannose PTS permease which phosphorylates the alpha-D-mannose. Alpha-D-mannose 6-phosphate interacts in a reversible reaction with a phosphomannomutase to produce a alpha-D-mannose 1-phosphate. This compound in turn with a hydrogen ion and gtp undergoes a reaction with a mannose-1-phosphate guanylyltransferase, releasing a pyrophosphate and producing a guanosine diphosphate mannose. Guanosine diphosphate mannose interacts with gdp-mannose 4,6-dehydratase releasing a water, and gdp-4-dehydro-6-deoxy-D-mannose. This compound in turn with hydrogen ion and NADPH interact with GDP-L-fucose synthase releasing NADP and producing a GDP-L-fucose. The Alpha-D-Glucose 6-phosphate interacts in a reversible reaction with phosphoglucomutase-1 to produce a alpha-D-glucose 1-phosphate. This in turn with UTP and hydrogen ion interact with UTP--glucose-1-phosphate uridyleltransferase releasing a pyrophosphate and UDP-glucose. UDP-glucose can either interact with galactose-1-phosphate uridylyltransferase to produce a UDP-galactose or in turn with NAD and water interact with UDP-glucose 6-dehydrogenase releasing a NADH and a hydrogen ion and producing a UDP-glucuronate. GDP-L-fucose, UDP-glucose, UDP-galactose and UDP-glucuronate are sugars that need to be activated in the form of nucleotide sugar prior to their assembly into colanic acid, also known as M antigen. Colanic acid is an extracellular polysaccharide which has been linked to a cluster of 19 genes(wca). PW000951 Metabolic polymyxin resistance UDP-glucuronic acid compound undergoes a NAD dependent reaction through a bifunctional polymyxin resistance protein to produce UDP-Beta-L-threo-pentapyranos-4-ulose. This compound then reacts with L-glutamic acid through a UDP-4-amino-4-deoxy-L-arabinose--oxoglutarate aminotransferase to produce an oxoglutaric acid and UDP-4-amino-4-deoxy-beta-L-arabinopyranose The latter compound interacts with a N10-formyl-tetrahydrofolate through a bifunctional polymyxin resistance protein ArnA, resulting in a tetrahydrofolate, a hydrogen ion and a UDP-4-deoxy-4-formamido-beta-L-arabinopyranose, which in turn reacts with a product of the methylerythritol phosphate and polysoprenoid biosynthesis pathway, di-trans,octa-cis-undecaprenyl phosphate to produce a 4-deoxy-4-formamido-alpha-L-arabinopyranosyl ditrans, octacis-undecaprenyl phosphate. The compound 4-deoxy-4-formamido-alpha-L-arabinopyranosyl ditrans, octacis-undecaprenyl phosphate hypothetically reacts with water and results in the release of a formic acid and 4-amino-4-deoxy-α-L-arabinopyranosyl ditrans,octacis-undecaprenyl phosphate which in turn reacts with a KDO2-lipid A through a 4-amino-4-deoxy-L-arabinose transferase resulting in the release of a di-trans,octa-cis-undecaprenyl phosphate and a L-Ara4N-modified KDO2-Lipid A PW002052 Metabolic Specdb::CMs 11659 Specdb::CMs 37850 Specdb::CMs 282532 Specdb::CMs 391888 Specdb::CMs 391889 Specdb::CMs 391890 Specdb::CMs 391891 Specdb::CMs 391892 Specdb::CMs 391893 Specdb::CMs 391894 Specdb::CMs 391895 Specdb::CMs 391896 Specdb::CMs 391897 Specdb::CMs 391898 Specdb::CMs 391899 Specdb::CMs 391900 Specdb::CMs 391901 Specdb::CMs 391902 Specdb::CMs 391903 Specdb::CMs 391904 Specdb::CMs 391905 Specdb::CMs 391906 Specdb::CMs 391907 Specdb::CMs 391908 Specdb::CMs 391909 Specdb::NmrOneD 5142 Specdb::NmrOneD 5143 Specdb::NmrOneD 145850 Specdb::NmrOneD 145851 Specdb::NmrOneD 145852 Specdb::NmrOneD 145853 Specdb::NmrOneD 145854 Specdb::NmrOneD 145855 Specdb::NmrOneD 145856 Specdb::NmrOneD 145857 Specdb::NmrOneD 145858 Specdb::NmrOneD 145859 Specdb::NmrOneD 145860 Specdb::NmrOneD 145861 Specdb::NmrOneD 145862 Specdb::NmrOneD 145863 Specdb::NmrOneD 145864 Specdb::NmrOneD 145865 Specdb::NmrOneD 145866 Specdb::NmrOneD 145867 Specdb::NmrOneD 145868 Specdb::NmrOneD 145869 Specdb::MsMs 26240 Specdb::MsMs 26241 Specdb::MsMs 26242 Specdb::MsMs 32798 Specdb::MsMs 32799 Specdb::MsMs 32800 Specdb::MsMs 2255773 Specdb::MsMs 2256872 Specdb::MsMs 2257736 Specdb::MsMs 2258884 Specdb::MsMs 2259675 Specdb::MsMs 2452234 Specdb::MsMs 2452235 Specdb::MsMs 2452236 Specdb::MsMs 2483548 Specdb::MsMs 2483549 Specdb::MsMs 2483550 HMDB00935 16522 C00167 17200 UGA Uridine diphosphate glucuronic acid 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 Ghosal A, Hapangama N, Yuan Y, Achanfuo-Yeboah J, Iannucci R, Chowdhury S, Alton K, Patrick JE, Zbaida S: Identification of human UDP-glucuronosyltransferase enzyme(s) responsible for the glucuronidation of ezetimibe (Zetia). Drug Metab Dispos. 2004 Mar;32(3):314-20. 14977865 Quintus J, Kovar KA, Link P, Hamacher H: Urinary excretion of arbutin metabolites after oral administration of bearberry leaf extracts. Planta Med. 2005 Feb;71(2):147-52. 15729623 Cappiello M, Giuliani L, Rane A, Pacifici GM: Uridine 5'-diphosphoglucuronic acid (UDPGLcUA) in the human fetal liver, kidney and placenta. Eur J Drug Metab Pharmacokinet. 2000 Jul-Dec;25(3-4):161-3. 11420884 Huskey SW, Doss GA, Miller RR, Schoen WR, Chiu SH: N-glucuronidation reactions. II. Relative N-glucuronidation reactivity of methylbiphenyl tetrazole, methylbiphenyl triazole, and methylbiphenyl imidazole in rat, monkey, and human hepatic microsomes. Drug Metab Dispos. 1994 Jul-Aug;22(4):651-8. 7956743 Alkharfy KM, Frye RF: High-performance liquid chromatographic assay for acetaminophen glucuronide in human liver microsomes. J Chromatogr B Biomed Sci Appl. 2001 Apr 5;753(2):303-8. 11334344 Hagenauer B, Salamon A, Thalhammer T, Kunert O, Haslinger E, Klingler P, Senderowicz AM, Sausville EA, Jager W: In vitro glucuronidation of the cyclin-dependent kinase inhibitor flavopiridol by rat and human liver microsomes: involvement of UDP-glucuronosyltransferases 1A1 and 1A9. Drug Metab Dispos. 2001 Apr;29(4 Pt 1):407-14. 11259324 Cappiello M, Giuliani L, Pacifici GM: Distribution of UDP-glucuronosyltransferase and its endogenous substrate uridine 5'-diphosphoglucuronic acid in human tissues. Eur J Clin Pharmacol. 1991;41(4):345-50. 1804651 Fondeur-Gelinotte M, Lattard V, Oriol R, Mollicone R, Jacquinet JC, Mulliert G, Gulberti S, Netter P, Magdalou J, Ouzzine M, Fournel-Gigleux S: Phylogenetic and mutational analyses reveal key residues for UDP-glucuronic acid binding and activity of beta1,3-glucuronosyltransferase I (GlcAT-I). Protein Sci. 2006 Jul;15(7):1667-78. 16815917 Clinical Guide to Laboratory Tests, 2nd Ed. Norbert W. Tietz 1990 Simon, Ethan S.; Grabowski, Sven; Whitesides, George M. Convenient syntheses of cytidine 5'-triphosphate, guanosine 5'-triphosphate, and uridine 5'-triphosphate and their use in the preparation of UDP-glucose, UDP-glucuronic acid, and GDP-mannose. Journal Protein ushA P07024 USHA_ECOLI ushA http://ecmdb.ca/proteins/P07024.xml UDP-glucose 6-dehydrogenase P76373 UDG_ECOLI ugd http://ecmdb.ca/proteins/P76373.xml Bifunctional polymyxin resistance protein ArnA P77398 ARNA_ECOLI arnA http://ecmdb.ca/proteins/P77398.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 UDP-Glucuronic acid + NAD > UDP-beta-L-Threo-pentapyranos-4-ulose + Carbon dioxide + NADH UDP-Glucose + 2 NAD + Water > UDP-Glucuronic acid +2 NADH Water + 2 NAD + UDP-Glucose <>3 Hydrogen ion +2 NADH + Uridine diphosphate glucuronic acid + UDP-Glucuronic acid R00286 UGD-RXN UDP-Glucose + 2 NAD + Water > UDP-Glucuronic acid +2 NADH +3 Hydrogen ion PW_R003355 UDP-Glucuronic acid + NAD > Carbon dioxide + NADH + UDP-β-L-threo-pentapyranos-4-ulose PW_R003356