2.0 2012-05-31 10:25:53 -0600 2015-09-13 12:56:07 -0600 ECMDB00295 M2MDB000123 Uridine 5'-diphosphate Uridine 5'-diphosphate, also known as UDP, is an uracil nucleotide containing a pyrophosphate group esterified to C5 of the sugar moiety. UDP is an important extracellular pyrimidine signaling molecule that mediates diverse biological effects via P1 and P2 purinergic receptors, such as the uptake of thymidine and proliferation of gliomas. (PMID: 14558596) UDP induces intracellular Ca(2+) responses and oscillations in HeLa cells, due to the activation of P2Ys (G-protein coupled ATP receptors). (PMID: 1257952) 5'-UDP UDP Uridine 5'-diphosphate Uridine 5'-diphosphoric acid Uridine 5'-pyrophosphate Uridine 5'-pyrophosphorate Uridine 5'-pyrophosphoric acid Uridine diphosphate Uridine diphosphoric acid Uridine pyrophosphate Uridine pyrophosphoric acid Uridine-5'-diphosphate Uridine-5'-diphosphoric acid Uridine-diphosphate Uridine-diphosphoric acid C9H14N2O12P2 404.1612 404.002196946 [({[(2R,3S,4R,5R)-5-(2,4-dioxo-1,2,3,4-tetrahydropyrimidin-1-yl)-3,4-dihydroxyoxolan-2-yl]methoxy}(hydroxy)phosphoryl)oxy]phosphonic acid UDP 58-98-0 O[C@H]1[C@@H](O)[C@@H](O[C@@H]1COP(O)(=O)OP(O)(O)=O)N1C=CC(=O)NC1=O InChI=1S/C9H14N2O12P2/c12-5-1-2-11(9(15)10-5)8-7(14)6(13)4(22-8)3-21-25(19,20)23-24(16,17)18/h1-2,4,6-8,13-14H,3H2,(H,19,20)(H,10,12,15)(H2,16,17,18)/t4-,6-,7-,8-/m1/s1 XCCTYIAWTASOJW-XVFCMESISA-N Solid Cytosol logp -0.94 ALOGPS logs -1.66 ALOGPS solubility 8.89e+00 g/l ALOGPS logp -3 ChemAxon pka_strongest_acidic 1.77 ChemAxon pka_strongest_basic -3.7 ChemAxon iupac [({[(2R,3S,4R,5R)-5-(2,4-dioxo-1,2,3,4-tetrahydropyrimidin-1-yl)-3,4-dihydroxyoxolan-2-yl]methoxy}(hydroxy)phosphoryl)oxy]phosphonic acid ChemAxon average_mass 404.1612 ChemAxon mono_mass 404.002196946 ChemAxon smiles O[C@H]1[C@@H](O)[C@@H](O[C@@H]1COP(O)(=O)OP(O)(O)=O)N1C=CC(=O)NC1=O ChemAxon formula C9H14N2O12P2 ChemAxon inchi InChI=1S/C9H14N2O12P2/c12-5-1-2-11(9(15)10-5)8-7(14)6(13)4(22-8)3-21-25(19,20)23-24(16,17)18/h1-2,4,6-8,13-14H,3H2,(H,19,20)(H,10,12,15)(H2,16,17,18)/t4-,6-,7-,8-/m1/s1 ChemAxon inchikey XCCTYIAWTASOJW-XVFCMESISA-N ChemAxon polar_surface_area 212.39 ChemAxon refractivity 74.31 ChemAxon polarizability 30.43 ChemAxon rotatable_bond_count 6 ChemAxon acceptor_count 10 ChemAxon donor_count 6 ChemAxon physiological_charge -2 ChemAxon formal_charge 0 ChemAxon Pyrimidine metabolism The metabolism of pyrimidines begins with L-glutamine interacting with water molecule and a hydrogen carbonate through an ATP driven carbamoyl phosphate synthetase resulting in a hydrogen ion, an ADP, a phosphate, an L-glutamic acid and a carbamoyl phosphate. The latter compound interacts with an L-aspartic acid through a aspartate transcarbamylase resulting in a phosphate, a hydrogen ion and a N-carbamoyl-L-aspartate. The latter compound interacts with a hydrogen ion through a dihydroorotase resulting in the release of a water molecule and a 4,5-dihydroorotic acid. This compound interacts with an ubiquinone-1 through a dihydroorotate dehydrogenase, type 2 resulting in a release of an ubiquinol-1 and an orotic acid. The orotic acid then interacts with a phosphoribosyl pyrophosphate through a orotate phosphoribosyltransferase resulting in a pyrophosphate and an orotidylic acid. The latter compound then interacts with a hydrogen ion through an orotidine-5 '-phosphate decarboxylase, resulting in an release of carbon dioxide and an Uridine 5' monophosphate. The Uridine 5' monophosphate process to get phosphorylated by an ATP driven UMP kinase resulting in the release of an ADP and an Uridine 5--diphosphate. Uridine 5-diphosphate can be metabolized in multiple ways in order to produce a Deoxyuridine triphosphate. 1.-Uridine 5-diphosphate interacts with a reduced thioredoxin through a ribonucleoside diphosphate reductase 1 resulting in the release of a water molecule and an oxidized thioredoxin and an dUDP. The dUDP is then phosphorylated by an ATP through a nucleoside diphosphate kinase resulting in the release of an ADP and a DeoxyUridine triphosphate. 2.-Uridine 5-diphosphate interacts with a reduced NrdH glutaredoxin-like protein through a Ribonucleoside-diphosphate reductase 1 resulting in a release of a water molecule, an oxidized NrdH glutaredoxin-like protein and a dUDP. The dUDP is then phosphorylated by an ATP through a nucleoside diphosphate kinase resulting in the release of an ADP and a DeoxyUridine triphosphate. 3.-Uridine 5-diphosphate is phosphorylated by an ATP-driven nucleoside diphosphate kinase resulting in an ADP and an Uridinetriphosphate. The latter compound interacts with a reduced flavodoxin through ribonucleoside-triphosphate reductase resulting in the release of an oxidized flavodoxin, a water molecule and a Deoxyuridine triphosphate 4.-Uridine 5-diphosphate is phosphorylated by an ATP-driven nucleoside diphosphate kinase resulting in an ADP and an Uridinetriphosphate The uridine triphosphate interacts with a L-glutamine and a water molecule through an ATP driven CTP synthase resulting in an ADP, a phosphate, a hydrogen ion, an L-glutamic acid and a cytidine triphosphate. The cytidine triphosphate interacts with a reduced flavodoxin through a ribonucleoside-triphosphate reductase resulting in the release of a water molecule, an oxidized flavodoxin and a dCTP. The dCTP interacts with a water molecule and a hydrogen ion through a dCTP deaminase resulting in a release of an ammonium molecule and a Deoxyuridine triphosphate. 5.-Uridine 5-diphosphate is phosphorylated by an ATP-driven nucleoside diphosphate kinase resulting in an ADP and an Uridinetriphosphate The uridine triphosphate interacts with a L-glutamine and a water molecule through an ATP driven CTP synthase resulting in an ADP, a phosphate, a hydrogen ion, an L-glutamic acid and a cytidine triphosphate. The cytidine triphosphate then interacts spontaneously with a water molecule resulting in the release of a phosphate, a hydrogen ion and a CDP. The CDP then interacts with a reduced NrdH glutaredoxin-like protein through a ribonucleoside-diphosphate reductase 2 resulting in the release of a water molecule, an oxidized NrdH glutaredoxin-like protein and a dCDP. The dCDP is then phosphorylated through an ATP driven nucleoside diphosphate kinase resulting in an ADP and a dCTP. The dCTP interacts with a water molecule and a hydrogen ion through a dCTP deaminase resulting in a release of an ammonium molecule and a Deoxyuridine triphosphate. 6.-Uridine 5-diphosphate is phosphorylated by an ATP-driven nucleoside diphosphate kinase resulting in an ADP and an Uridinetriphosphate The uridine triphosphate interacts with a L-glutamine and a water molecule through an ATP driven CTP synthase resulting in an ADP, a phosphate, a hydrogen ion, an L-glutamic acid and a cytidine triphosphate. The cytidine triphosphate then interacts spontaneously with a water molecule resulting in the release of a phosphate, a hydrogen ion and a CDP. The CDP interacts with a reduced thioredoxin through a ribonucleoside diphosphate reductase 1 resulting in a release of a water molecule, an oxidized thioredoxin and a dCDP. The dCDP is then phosphorylated through an ATP driven nucleoside diphosphate kinase resulting in an ADP and a dCTP. The dCTP interacts with a water molecule and a hydrogen ion through a dCTP deaminase resulting in a release of an ammonium molecule and a Deoxyuridine triphosphate. The deoxyuridine triphosphate then interacts with a water molecule through a nucleoside triphosphate pyrophosphohydrolase resulting in a release of a hydrogen ion, a phosphate and a dUMP. The dUMP then interacts with a methenyltetrahydrofolate through a thymidylate synthase resulting in a dihydrofolic acid and a 5-thymidylic acid. Then 5-thymidylic acid is then phosphorylated through a nucleoside diphosphate kinase resulting in the release of an ADP and thymidine 5'-triphosphate. PW000942 ec00240 Metabolic 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 Amino sugar and nucleotide sugar metabolism ec00520 Peptidoglycan biosynthesis ec00550 Lipopolysaccharide biosynthesis E. coli lipid A is synthesized on the cytoplasmic surface of the inner membrane. The pathway can start from the fructose 6-phosphate that is either produced in the glycolysis and pyruvate dehydrogenase or be obtained from the interaction with D-fructose interacting with a mannose PTS permease. Fructose 6-phosphate interacts with L-glutamine through a D-fructose-6-phosphate aminotransferase resulting into a L-glutamic acid and a glucosamine 6-phosphate. The latter compound is isomerized through a phosphoglucosamine mutase resulting a glucosamine 1-phosphate. This compound is acetylated, interacting with acetyl-CoA through a bifunctional protein glmU resulting in a Coenzyme A, hydrogen ion and N-acetyl-glucosamine 1-phosphate. This compound interact with UTP and hydrogen ion through the bifunctional protein glmU resulting in a pyrophosphate and a UDP-N-acetylglucosamine. This compound interacts with (3R)-3-hydroxymyristoyl-[acp] through an UDP-N-acetylglucosamine acyltransferase resulting in a holo-[acp] and a UDP-3-O[(3R)-3-hydroxymyristoyl]-N-acetyl-alpha-D-glucosamine. This compound interacts with water through UDP-3-O-acyl-N-acetylglucosamine deacetylase resulting in an acetic acid and UDP-3-O-(3-hydroxymyristoyl)-α-D-glucosamine. The latter compound interacts with (3R)-3-hydroxymyristoyl-[acp] through UDP-3-O-(R-3-hydroxymyristoyl)-glucosamine N-acyltransferase releasing a hydrogen ion, a holo-acp and UDP-2-N,3-O-bis[(3R)-3-hydroxytetradecanoyl]-α-D-glucosamine. The latter compound is hydrolase by interacting with water and a UDP-2,3-diacylglucosamine hydrolase resulting in UMP, hydrogen ion and 2,3-bis[(3R)-3-hydroxymyristoyl]-α-D-glucosaminyl 1-phosphate. This last compound then interacts with a UDP-2-N,3-O-bis[(3R)-3-hydroxytetradecanoyl]-α-D-glucosamine through a lipid A disaccharide synthase resulting in a release of UDP, hydrogen ion and a lipid A disaccharide. The lipid A disaccharide is phosphorylated by an ATP mediated tetraacyldisaccharide 4'-kinase resulting in the release of hydrogen ion and lipid IVA. A D-ribulose 5-phosphate is isomerized with D-arabinose 5-phosphate isomerase 2 to result in a D-arabinose 5-phosphate. This compounds interacts with water and phosphoenolpyruvic acid through a 3-deoxy-D-manno-octulosonate 8-phosphate synthase resulting in the release of phosphate and 3-deoxy-D-manno-octulosonate 8-phosphate. This compound interacts with water through a 3-deoxy-D-manno-octulosonate 8-phosphate phosphatase thus releasing a phosphate and a 3-deoxy-D-manno-octulosonate. The latter compound interacts with CTP through a 3-deoxy-D-manno-octulosonate cytidylyltransferase resulting in a pyrophosphate and CMP-3-deoxy-α-D-manno-octulosonate. CMP-3-deoxy-α-D-manno-octulosonate and lipid IVA interact with each other through a KDO transferase resulting in CMP, hydrogen ion and alpha-Kdo-(2-->6)-lipid IVA. The latter compound reacts with CMP-3-deoxy-α-D-manno-octulosonate through a KDO transferase resulting in a CMP, hydrogen ion, and a a-Kdo-(2->4)-a-Kdo-(2->6)-lipid IVA. The latter compound interacts with a dodecanoyl-[acp] lauroyl acyltransferase resulting in a holo-[acp] and a (KDO)2-(lauroyl)-lipid IVA. The latter compound reacts with a myristoyl-[acp] through a myristoyl-acyl carrier protein (ACP)-dependent acyltransferase resulting in a holo-[acp], (KDO)2-lipid A. The latter compound reacts with ADP-L-glycero-beta-D-manno-heptose through ADP-heptose:LPS heptosyltransferase I resulting hydrogen ion, ADP, heptosyl-KDO2-lipid A. The latter compound interacts with ADP-L-glycero-beta-D-manno-heptose through ADP-heptose:LPS heptosyltransferase II resulting in ADP, hydrogen ion and (heptosyl)2-Kdo2-lipid A. The latter compound UDP-glucose interacts with (heptosyl)2-Kdo2-lipid A resulting in UDP, hydrogen ion and glucosyl-(heptosyl)2-Kdo2-lipid A. Glucosyl-(heptosyl)2-Kdo2-lipid A (Escherichia coli) is phosphorylated through an ATP-mediated lipopolysaccharide core heptose (I) kinase resulting in ADP, hydrogen ion and glucosyl-(heptosyl)2-Kdo2-lipid A-phosphate. The latter compound interacts with ADP-L-glycero-beta-D-manno-heptose through a lipopolysaccharide core heptosyl transferase III resulting in ADP, hydrogen ion, and glucosyl-(heptosyl)3-Kdo2-lipid A-phosphate. The latter compound is phosphorylated through an ATP-driven lipopolysaccharide core heptose (II) kinase resulting in ADP, hydrogen ion and glucosyl-(heptosyl)3-Kdo2-lipid A-bisphosphate. The latter compound interacts with UDP-alpha-D-galactose through a UDP-D-galactose:(glucosyl)lipopolysaccharide-1,6-D-galactosyltransferase resulting in a UDP, a hydrogen ion and a galactosyl-glucosyl-(heptosyl)3-Kdo2-lipid A-bisphosphate. The latter compound interacts with UDP-glucose through a (glucosyl)LPS α-1,3-glucosyltransferase resulting in a hydrogen ion, a UDP and galactosyl-(glucosyl)2-(heptosyl)3-Kdo2-lipid A-bisphosphate. This compound then interacts with UDP-glucose through a UDP-glucose:(glucosyl)LPS α-1,2-glucosyltransferase resulting in UDP, a hydrogen ion and galactosyl-(glucosyl)3-(heptosyl)3-Kdo2-lipid A-bisphosphate. This compound then interacts with ADP-L-glycero-beta-D-manno-heptose through a lipopolysaccharide core biosynthesis; heptosyl transferase IV; probably hexose transferase resulting in a Lipid A-core. A lipid A-core is then exported into the periplasmic space by a lipopolysaccharide ABC transporter. The lipid A-core is then flipped to the outer surface of the inner membrane by the ATP-binding cassette (ABC) transporter, MsbA. An additional integral membrane protein, YhjD, has recently been implicated in LPS export across the IM. The smallest LPS derivative that supports viability in E. coli is lipid IVA. However, it requires mutations in either MsbA or YhjD, to suppress the normally lethal consequence of an incomplete lipid A . Recent studies with deletion mutants implicate the periplasmic protein LptA, the cytosolic protein LptB, and the IM proteins LptC, LptF, and LptG in the subsequent transport of nascent LPS to the outer membrane (OM), where the LptD/LptE complex flips LPS to the outer surface. PW000831 ec00540 Metabolic 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 Secondary Metabolites: enterobacterial common antigen biosynthesis The biosynthesis of a enterobacterial common antigen can begin with a di-trans,octa-cis-undecaprenyl phosphate interacts with a Uridine diphosphate-N-acetylglucosamine through undecaprenyl-phosphate α-N-acetylglucosaminyl transferase resulting in a N-acetyl-α-D-glucosaminyl-diphospho-ditrans,octacis-undecaprenol and a Uridine 5'-monophosphate. The N-acetyl-α-D-glucosaminyl-diphospho-ditrans,octacis-undecaprenol then reacts with an UDP-ManNAcA from the Amino sugar and nucleotide sugar metabolism pathway. This reaction is metabolized by a UDP-N-acetyl-D-mannosaminuronic acid transferase resulting in a uridine 5' diphosphate, a hydrogen ion and a Undecaprenyl N-acetyl-glucosaminyl-N-acetyl-mannosaminuronate-4-acetamido-4,6-dideoxy-D-galactose pyrophosphate. Glucose 1 phosphate can be metabolize by interacting with a hydrogen ion and a thymidine 5-triphosphate by either reacting with a dTDP-glucose pyrophosphorylase or a dTDP-glucose pyrophosphorylase 2 resulting in the release of a pyrophosphate and a dTDP-D-glucose. The latter compound is then dehydrated through an dTDP-glucose 4,6-dehydratase 2 resulting in water and dTDP-4-dehydro-6-deoxy-D-glucose. The latter compound interacts with L-glutamic acid through a dTDP-4-dehydro-6-deoxy-D-glucose transaminase resulting in the release of oxoglutaric acid and dTDP-thomosamine. The latter compound interacts with acetyl-coa through a dTDP-fucosamine acetyltransferase resulting in a Coenzyme A, a hydrogen Ion and a TDP-Fuc4NAc. Undecaprenyl N-acetyl-glucosaminyl-N-acetyl-mannosaminuronate-4-acetamido-4,6-dideoxy-D-galactose pyrophosphate then interacts with a TDP--Fuc4NAc through a 4-acetamido-4,6-dideoxy-D-galactose transferase resulting in a hydrogen ion, a dTDP and a Undecaprenyl N-acetyl-glucosaminyl-N-acetyl-mannosaminuronate-4-acetamido-4,6-dideoxy-D-galactose pyrophosphate. This compound is then transported through a protein wzxE into the periplasmic space so that it can be incorporated into the outer membrane Enterobacterial common antigen (ECA) is an outer membrane glycolipid common to all members of Enterobacteriaceae. ECA is a unique cell surface antigen that can be found in the outer leaflet of the outer membrane. The carbohydrate portion consists of N-acetyl-glucosamine, N-acetyl-D-mannosaminuronic acid and 4-acetamido-4,6-dideoxy-D-galactose. These amino sugars form trisaccharide repeat units which are part of linear heteropolysaccharide chains. PW000959 Metabolic peptidoglycan biosynthesis I Peptidoglycan is a net-like polymer which surrounds the cytoplasmic membrane of most bacteria and functions to maintain cell shape and prevent rupture due to the internal turgor.In E. coli K-12, the peptidoglycan consists of glycan strands of alternating subunits of N-acetylglucosamine (GlcNAc) and N-acetylmuramic acid (MurNAc) which are cross-linked by short peptides. The pathway for constructing this net involves two cell compartments: cytoplasm and periplasmic space. The pathway starts with a beta-D-fructofuranose going through a mannose PTS permease, phosphorylating the compund and producing a beta-D-fructofuranose 6 phosphate. This compound can be obtained from the glycolysis and pyruvate dehydrogenase or from an isomerization reaction of Beta-D-glucose 6-phosphate through a glucose-6-phosphate isomerase.The compound Beta-D-fructofuranose 6 phosphate and L-Glutamine react with a glucosamine fructose-6-phosphate aminotransferase, thus producing a glucosamine 6-phosphate and a l-glutamic acid. The glucosamine 6-phosphate interacts with phosphoglucosamine mutase in a reversible reaction producing glucosamine-1P. Glucosamine-1p and acetyl coa undergo acetylation throuhg a bifunctional protein glmU releasing Coa and a hydrogen ion and producing a N-acetyl-glucosamine 1-phosphate. Glmu, being a bifunctional protein, follows catalyze the interaction of N-acetyl-glucosamine 1-phosphate, hydrogen ion and UTP into UDP-N-acetylglucosamine and pyrophosphate. UDP-N-acetylglucosamine then interacts with phosphoenolpyruvic acid and a UDP-N acetylglucosamine 1- carboxyvinyltransferase realeasing a phosphate and the compound UDP-N-acetyl-alpha-D-glucosamine-enolpyruvate. This compound undergoes a NADPH dependent reduction producing a UDP-N-acetyl-alpha-D-muramate through a UDP-N-acetylenolpyruvoylglucosamine reductase. UDP-N-acetyl-alpha-D-muramate and L-alanine react in an ATP-mediated ligation through a UDP-N-acetylmuramate-alanine ligase releasing an ADP, hydrogen ion, a phosphate and a UDP-N-acetylmuramoyl-L-alanine. This compound interacts with D-glutamic acid and ATP through UDP-N-acetylmuramoylalanine-D-glutamate ligase releasing ADP, A phosphate and UDP-N-acetylmuramoyl-L-alanyl-D-glutamate. The latter compound then interacts with meso-diaminopimelate in an ATP mediated ligation through a UDP-N-acetylmuramoylalanine-D-glutamate-2,6-diaminopimelate ligase resulting in ADP, phosphate, hydrogen ion and UDP-N-Acetylmuramoyl-L-alanyl-D-gamma-glutamyl-meso-2,6-diaminopimelate. This compound in turn with D-alanyl-D-alanine react in an ATP-mediated ligation through UDP-N-Acetylmuramoyl-tripeptide-D-alanyl-D-alanine ligase to produce UDP-N-acetyl-alpha-D-muramoyl-L-alanyl-gama-D-glutamyl-meso-2,6-diaminopimeloyl-Dalanyl-D-alanine and hydrogen ion, ADP, phosphate. UDP-N-acetyl-alpha-D-muramoyl-L-alanyl-gama-D-glutamyl-meso-2,6-diaminopimeloyl-Dalanyl-D-alanine interacts with di-trans,octa-cis-undecaprenyl phosphate through a phospho-N-acetylmuramoyl-pentapeptide-transferase, resulting in UMP and Undecaprenyl-diphospho-N-acetylmuramoyl-L-alanyl-D-glutamyl-meso-2,6-diaminopimeloyl-D-alanyl-D-alanine which in turn reacts with a UDP-N-acetylglucosamine through a N-acetylglucosaminyl transferase to produce a hydrogen, UDP and ditrans,octacis-undecaprenyldiphospho-N-acetyl-(N-acetylglucosaminyl)muramoyl-L-alanyl-gamma-D-glutamyl-meso-2,6-diaminopimeloyl-D-alanyl-D-alanine. This compound ends the cytoplasmic part of the pathway. ditrans,octacis-undecaprenyldiphospho-N-acetyl-(N-acetylglucosaminyl)muramoyl-L-alanyl-gamma-D-glutamyl-meso-2,6-diaminopimeloyl-D-alanyl-D-alanine is transported through a lipi II flippase. Once in the periplasmic space, the compound reacts with a penicillin binding protein 1A prodducing a peptidoglycan dimer, a hydrogen ion, and UDP. The peptidoglycan dimer then reacts with a penicillin binding protein 1B producing a peptidoglycan with D,D, cross-links and a D-alanine. PW000906 Metabolic lipopolysaccharide biosynthesis II E. coli lipid A is synthesized on the cytoplasmic surface of the inner membrane. The pathway can start from the fructose 6-phosphate that is either produced in the glycolysis and pyruvate dehydrogenase or be obtained from the interaction with D-fructose interacting with a mannose PTS permease. Fructose 6-phosphate interacts with L-glutamine through a D-fructose-6-phosphate aminotransferase resulting into a L-glutamic acid and a glucosamine 6-phosphate. The latter compound is isomerized through a phosphoglucosamine mutase resulting a glucosamine 1-phosphate. This compound is acetylated, interacting with acetyl-CoA through a bifunctional protein glmU resulting in a Coenzyme A, hydrogen ion and N-acetyl-glucosamine 1-phosphate. This compound interact with UTP and hydrogen ion through the bifunctional protein glmU resulting in a pyrophosphate and a UDP-N-acetylglucosamine. This compound interacts with (3R)-3-hydroxymyristoyl-[acp] through an UDP-N-acetylglucosamine acyltransferase resulting in a holo-[acp] and a UDP-3-O[(3R)-3-hydroxymyristoyl]-N-acetyl-alpha-D-glucosamine. This compound interacts with water through UDP-3-O-acyl-N-acetylglucosamine deacetylase resulting in an acetic acid and UDP-3-O-(3-hydroxymyristoyl)-α-D-glucosamine. The latter compound interacts with (3R)-3-hydroxymyristoyl-[acp] through UDP-3-O-(R-3-hydroxymyristoyl)-glucosamine N-acyltransferase releasing a hydrogen ion, a holo-acp and UDP-2-N,3-O-bis[(3R)-3-hydroxytetradecanoyl]-α-D-glucosamine. The latter compound is hydrolase by interacting with water and a UDP-2,3-diacylglucosamine hydrolase resulting in UMP, hydrogen ion and 2,3-bis[(3R)-3-hydroxymyristoyl]-α-D-glucosaminyl 1-phosphate. This last compound then interacts with a UDP-2-N,3-O-bis[(3R)-3-hydroxytetradecanoyl]-α-D-glucosamine through a lipid A disaccharide synthase resulting in a release of UDP, hydrogen ion and a lipid A disaccharide. The lipid A disaccharide is phosphorylated by an ATP mediated tetraacyldisaccharide 4'-kinase resulting in the release of hydrogen ion and lipid IVA. A D-ribulose 5-phosphate is isomerized with D-arabinose 5-phosphate isomerase 2 to result in a D-arabinose 5-phosphate. This compounds interacts with water and phosphoenolpyruvic acid through a 3-deoxy-D-manno-octulosonate 8-phosphate synthase resulting in the release of phosphate and 3-deoxy-D-manno-octulosonate 8-phosphate. This compound interacts with water through a 3-deoxy-D-manno-octulosonate 8-phosphate phosphatase thus releasing a phosphate and a 3-deoxy-D-manno-octulosonate. The latter compound interacts with CTP through a 3-deoxy-D-manno-octulosonate cytidylyltransferase resulting in a pyrophosphate and CMP-3-deoxy-α-D-manno-octulosonate. CMP-3-deoxy-α-D-manno-octulosonate and lipid IVA interact with each other through a KDO transferase resulting in CMP, hydrogen ion and alpha-Kdo-(2-->6)-lipid IVA. The latter compound reacts with CMP-3-deoxy-α-D-manno-octulosonate through a KDO transferase resulting in a CMP, hydrogen ion, and a a-Kdo-(2->4)-a-Kdo-(2->6)-lipid IVA. The latter compound can either interact with a phosphoethanolamine resulting in a 1,2-diacyl-sn-glycerol and a phosphoethanolamine-Kdo2-lipid A which can be exported outside the cell, or it can interact with a dodecanoyl-[acp] lauroyl acyltransferase resulting in a holo-[acp] and a (KDO)2-(lauroyl)-lipid IVA. The latter compound reacts with a myristoyl-[acp] through a myristoyl-acyl carrier protein (ACP)-dependent acyltransferase resulting in a holo-[acp], (KDO)2-lipid A. The latter compound reacts with ADP-L-glycero-beta-D-manno-heptose through ADP-heptose:LPS heptosyltransferase I resulting hydrogen ion, ADP, heptosyl-KDO2-lipid A. The latter compound interacts with ADP-L-glycero-beta-D-manno-heptose through ADP-heptose:LPS heptosyltransferase II resulting in ADP, hydrogen ion and (heptosyl)2-Kdo2-lipid A. The latter compound UDP-glucose interacts with (heptosyl)2-Kdo2-lipid A resulting in UDP, hydrogen ion and glucosyl-(heptosyl)2-Kdo2-lipid A. Glucosyl-(heptosyl)2-Kdo2-lipid A (Escherichia coli) is phosphorylated through an ATP-mediated lipopolysaccharide core heptose (I) kinase resulting in ADP, hydrogen ion and glucosyl-(heptosyl)2-Kdo2-lipid A-phosphate. The latter compound interacts with ADP-L-glycero-beta-D-manno-heptose through a lipopolysaccharide core heptosyl transferase III resulting in ADP, hydrogen ion, and glucosyl-(heptosyl)3-Kdo2-lipid A-phosphate. The latter compound is phosphorylated through an ATP-driven lipopolysaccharide core heptose (II) kinase resulting in ADP, hydrogen ion and glucosyl-(heptosyl)3-Kdo2-lipid A-bisphosphate. The latter compound interacts with UDP-alpha-D-galactose through a UDP-D-galactose:(glucosyl)lipopolysaccharide-1,6-D-galactosyltransferase resulting in a UDP, a hydrogen ion and a galactosyl-glucosyl-(heptosyl)3-Kdo2-lipid A-bisphosphate. The latter compound interacts with UDP-glucose through a (glucosyl)LPS α-1,3-glucosyltransferase resulting in a hydrogen ion, a UDP and galactosyl-(glucosyl)2-(heptosyl)3-Kdo2-lipid A-bisphosphate. This compound then interacts with UDP-glucose through a UDP-glucose:(glucosyl)LPS α-1,2-glucosyltransferase resulting in UDP, a hydrogen ion and galactosyl-(glucosyl)3-(heptosyl)3-Kdo2-lipid A-bisphosphate. This compound then interacts with ADP-L-glycero-beta-D-manno-heptose through a lipopolysaccharide core biosynthesis; heptosyl transferase IV; probably hexose transferase resulting in a Lipid A-core. A lipid A-core is then exported into the periplasmic space by a lipopolysaccharide ABC transporter. The lipid A-core is then flipped to the outer surface of the inner membrane by the ATP-binding cassette (ABC) transporter, MsbA. An additional integral membrane protein, YhjD, has recently been implicated in LPS export across the IM. The smallest LPS derivative that supports viability in E. coli is lipid IVA. However, it requires mutations in either MsbA or YhjD, to suppress the normally lethal consequence of an incomplete lipid A . Recent studies with deletion mutants implicate the periplasmic protein LptA, the cytosolic protein LptB, and the IM proteins LptC, LptF, and LptG in the subsequent transport of nascent LPS to the outer membrane (OM), where the LptD/LptE complex flips LPS to the outer surface. PW001905 Metabolic Secondary Metabolites: enterobacterial common antigen biosynthesis 2 The biosynthesis of a enterobacterial common antigen can begin with a di-trans,octa-cis-undecaprenyl phosphate interacts with a Uridine diphosphate-N-acetylglucosamine through undecaprenyl-phosphate α-N-acetylglucosaminyl transferase resulting in a N-acetyl-α-D-glucosaminyl-diphospho-ditrans,octacis-undecaprenol and a Uridine 5'-monophosphate. The N-acetyl-α-D-glucosaminyl-diphospho-ditrans,octacis-undecaprenol then reacts with an UDP-ManNAcA from the Amino sugar and nucleotide sugar metabolism pathway. This reaction is metabolized by a UDP-N-acetyl-D-mannosaminuronic acid transferase resulting in a uridine 5' diphosphate, a hydrogen ion and a Undecaprenyl N-acetyl-glucosaminyl-N-acetyl-mannosaminuronate-4-acetamido-4,6-dideoxy-D-galactose pyrophosphate. Glucose 1 phosphate can be metabolize by interacting with a hydrogen ion and a thymidine 5-triphosphate by either reacting with a dTDP-glucose pyrophosphorylase or a dTDP-glucose pyrophosphorylase 2 resulting in the release of a pyrophosphate and a dTDP-D-glucose. The latter compound is then dehydrated through an dTDP-glucose 4,6-dehydratase 2 resulting in water and dTDP-4-dehydro-6-deoxy-D-glucose. The latter compound interacts with L-glutamic acid through a dTDP-4-dehydro-6-deoxy-D-glucose transaminase resulting in the release of oxoglutaric acid and dTDP-thomosamine. The latter compound interacts with acetyl-coa through a dTDP-fucosamine acetyltransferase resulting in a Coenzyme A, a hydrogen Ion and a TDP-Fuc4NAc. Undecaprenyl N-acetyl-glucosaminyl-N-acetyl-mannosaminuronate-4-acetamido-4,6-dideoxy-D-galactose pyrophosphate then interacts with a TDP--Fuc4NAc through a 4-acetamido-4,6-dideoxy-D-galactose transferase resulting in a hydrogen ion, a dTDP and a Undecaprenyl N-acetyl-glucosaminyl-N-acetyl-mannosaminuronate-4-acetamido-4,6-dideoxy-D-galactose pyrophosphate. This compound is then transported through a protein wzxE into the periplasmic space so that it can be incorporated into the outer membrane Enterobacterial common antigen (ECA) is an outer membrane glycolipid common to all members of Enterobacteriaceae. ECA is a unique cell surface antigen that can be found in the outer leaflet of the outer membrane. The carbohydrate portion consists of N-acetyl-glucosamine, N-acetyl-D-mannosaminuronic acid and 4-acetamido-4,6-dideoxy-D-galactose. These amino sugars form trisaccharide repeat units which are part of linear heteropolysaccharide chains. PW002045 Metabolic Secondary Metabolites: enterobacterial common antigen biosynthesis 3 The biosynthesis of a enterobacterial common antigen can begin with a di-trans,octa-cis-undecaprenyl phosphate interacts with a Uridine diphosphate-N-acetylglucosamine through undecaprenyl-phosphate α-N-acetylglucosaminyl transferase resulting in a N-acetyl-α-D-glucosaminyl-diphospho-ditrans,octacis-undecaprenol and a Uridine 5'-monophosphate. The N-acetyl-α-D-glucosaminyl-diphospho-ditrans,octacis-undecaprenol then reacts with an UDP-ManNAcA from the Amino sugar and nucleotide sugar metabolism pathway. This reaction is metabolized by a UDP-N-acetyl-D-mannosaminuronic acid transferase resulting in a uridine 5' diphosphate, a hydrogen ion and a Undecaprenyl N-acetyl-glucosaminyl-N-acetyl-mannosaminuronate-4-acetamido-4,6-dideoxy-D-galactose pyrophosphate. Glucose 1 phosphate can be metabolize by interacting with a hydrogen ion and a thymidine 5-triphosphate by either reacting with a dTDP-glucose pyrophosphorylase or a dTDP-glucose pyrophosphorylase 2 resulting in the release of a pyrophosphate and a dTDP-D-glucose. The latter compound is then dehydrated through an dTDP-glucose 4,6-dehydratase 2 resulting in water and dTDP-4-dehydro-6-deoxy-D-glucose. The latter compound interacts with L-glutamic acid through a dTDP-4-dehydro-6-deoxy-D-glucose transaminase resulting in the release of oxoglutaric acid and dTDP-thomosamine. The latter compound interacts with acetyl-coa through a dTDP-fucosamine acetyltransferase resulting in a Coenzyme A, a hydrogen Ion and a TDP-Fuc4NAc. Undecaprenyl N-acetyl-glucosaminyl-N-acetyl-mannosaminuronate-4-acetamido-4,6-dideoxy-D-galactose pyrophosphate then interacts with a TDP--Fuc4NAc through a 4-acetamido-4,6-dideoxy-D-galactose transferase resulting in a hydrogen ion, a dTDP and a Undecaprenyl N-acetyl-glucosaminyl-N-acetyl-mannosaminuronate-4-acetamido-4,6-dideoxy-D-galactose pyrophosphate. This compound is then transported through a protein wzxE into the periplasmic space so that it can be incorporated into the outer membrane Enterobacterial common antigen (ECA) is an outer membrane glycolipid common to all members of Enterobacteriaceae. ECA is a unique cell surface antigen that can be found in the outer leaflet of the outer membrane. The carbohydrate portion consists of N-acetyl-glucosamine, N-acetyl-D-mannosaminuronic acid and 4-acetamido-4,6-dideoxy-D-galactose. These amino sugars form trisaccharide repeat units which are part of linear heteropolysaccharide chains. PW002046 Metabolic lipopolysaccharide biosynthesis III E. coli lipid A is synthesized on the cytoplasmic surface of the inner membrane. The pathway can start from the fructose 6-phosphate that is either produced in the glycolysis and pyruvate dehydrogenase or be obtained from the interaction with D-fructose interacting with a mannose PTS permease. Fructose 6-phosphate interacts with L-glutamine through a D-fructose-6-phosphate aminotransferase resulting into a L-glutamic acid and a glucosamine 6-phosphate. The latter compound is isomerized through a phosphoglucosamine mutase resulting a glucosamine 1-phosphate. This compound is acetylated, interacting with acetyl-CoA through a bifunctional protein glmU resulting in a Coenzyme A, hydrogen ion and N-acetyl-glucosamine 1-phosphate. This compound interact with UTP and hydrogen ion through the bifunctional protein glmU resulting in a pyrophosphate and a UDP-N-acetylglucosamine. This compound interacts with (3R)-3-hydroxymyristoyl-[acp] through an UDP-N-acetylglucosamine acyltransferase resulting in a holo-[acp] and a UDP-3-O[(3R)-3-hydroxymyristoyl]-N-acetyl-alpha-D-glucosamine. This compound interacts with water through UDP-3-O-acyl-N-acetylglucosamine deacetylase resulting in an acetic acid and UDP-3-O-(3-hydroxymyristoyl)-α-D-glucosamine. The latter compound interacts with (3R)-3-hydroxymyristoyl-[acp] through UDP-3-O-(R-3-hydroxymyristoyl)-glucosamine N-acyltransferase releasing a hydrogen ion, a holo-acp and UDP-2-N,3-O-bis[(3R)-3-hydroxytetradecanoyl]-α-D-glucosamine. The latter compound is hydrolase by interacting with water and a UDP-2,3-diacylglucosamine hydrolase resulting in UMP, hydrogen ion and 2,3-bis[(3R)-3-hydroxymyristoyl]-α-D-glucosaminyl 1-phosphate. This last compound then interacts with a UDP-2-N,3-O-bis[(3R)-3-hydroxytetradecanoyl]-α-D-glucosamine through a lipid A disaccharide synthase resulting in a release of UDP, hydrogen ion and a lipid A disaccharide. The lipid A disaccharide is phosphorylated by an ATP mediated tetraacyldisaccharide 4'-kinase resulting in the release of hydrogen ion and lipid IVA. A D-ribulose 5-phosphate is isomerized with D-arabinose 5-phosphate isomerase 2 to result in a D-arabinose 5-phosphate. This compounds interacts with water and phosphoenolpyruvic acid through a 3-deoxy-D-manno-octulosonate 8-phosphate synthase resulting in the release of phosphate and 3-deoxy-D-manno-octulosonate 8-phosphate. This compound interacts with water through a 3-deoxy-D-manno-octulosonate 8-phosphate phosphatase thus releasing a phosphate and a 3-deoxy-D-manno-octulosonate. The latter compound interacts with CTP through a 3-deoxy-D-manno-octulosonate cytidylyltransferase resulting in a pyrophosphate and CMP-3-deoxy-α-D-manno-octulosonate. CMP-3-deoxy-α-D-manno-octulosonate and lipid IVA interact with each other through a KDO transferase resulting in CMP, hydrogen ion and alpha-Kdo-(2-->6)-lipid IVA. The latter compound reacts with CMP-3-deoxy-α-D-manno-octulosonate through a KDO transferase resulting in a CMP, hydrogen ion, and a a-Kdo-(2->4)-a-Kdo-(2->6)-lipid IVA. The latter compound can either react with a palmitoleoyl-acp through a palmitoleoyl acyltransferase resulting in the release of a holo-acyl carriere protein and a Kdo2-palmitoleoyl-lipid IVa which in turn reacts with a myristoyl-acp through a myristoyl-acp dependent acyltransferase resulting in a release of a holo-acp and a Kdo2-lipid A, cold adapted, or it can interact with a dodecanoyl-[acp] lauroyl acyltransferase resulting in a holo-[acp] and a (KDO)2-(lauroyl)-lipid IVA. The latter compound reacts with a myristoyl-[acp] through a myristoyl-acyl carrier protein (ACP)-dependent acyltransferase resulting in a holo-[acp], (KDO)2-lipid A. The latter compound reacts with ADP-L-glycero-beta-D-manno-heptose through ADP-heptose:LPS heptosyltransferase I resulting hydrogen ion, ADP, heptosyl-KDO2-lipid A. The latter compound interacts with ADP-L-glycero-beta-D-manno-heptose through ADP-heptose:LPS heptosyltransferase II resulting in ADP, hydrogen ion and (heptosyl)2-Kdo2-lipid A. The latter compound UDP-glucose interacts with (heptosyl)2-Kdo2-lipid A resulting in UDP, hydrogen ion and glucosyl-(heptosyl)2-Kdo2-lipid A. Glucosyl-(heptosyl)2-Kdo2-lipid A (Escherichia coli) is phosphorylated through an ATP-mediated lipopolysaccharide core heptose (I) kinase resulting in ADP, hydrogen ion and glucosyl-(heptosyl)2-Kdo2-lipid A-phosphate. The latter compound interacts with ADP-L-glycero-beta-D-manno-heptose through a lipopolysaccharide core heptosyl transferase III resulting in ADP, hydrogen ion, and glucosyl-(heptosyl)3-Kdo2-lipid A-phosphate. The latter compound is phosphorylated through an ATP-driven lipopolysaccharide core heptose (II) kinase resulting in ADP, hydrogen ion and glucosyl-(heptosyl)3-Kdo2-lipid A-bisphosphate. The latter compound interacts with UDP-alpha-D-galactose through a UDP-D-galactose:(glucosyl)lipopolysaccharide-1,6-D-galactosyltransferase resulting in a UDP, a hydrogen ion and a galactosyl-glucosyl-(heptosyl)3-Kdo2-lipid A-bisphosphate. The latter compound interacts with UDP-glucose through a (glucosyl)LPS α-1,3-glucosyltransferase resulting in a hydrogen ion, a UDP and galactosyl-(glucosyl)2-(heptosyl)3-Kdo2-lipid A-bisphosphate. This compound then interacts with UDP-glucose through a UDP-glucose:(glucosyl)LPS α-1,2-glucosyltransferase resulting in UDP, a hydrogen ion and galactosyl-(glucosyl)3-(heptosyl)3-Kdo2-lipid A-bisphosphate. This compound then interacts with ADP-L-glycero-beta-D-manno-heptose through a lipopolysaccharide core biosynthesis; heptosyl transferase IV; probably hexose transferase resulting in a Lipid A-core. A lipid A-core is then exported into the periplasmic space by a lipopolysaccharide ABC transporter. The lipid A-core is then flipped to the outer surface of the inner membrane by the ATP-binding cassette (ABC) transporter, MsbA. An additional integral membrane protein, YhjD, has recently been implicated in LPS export across the IM. The smallest LPS derivative that supports viability in E. coli is lipid IVA. However, it requires mutations in either MsbA or YhjD, to suppress the normally lethal consequence of an incomplete lipid A . Recent studies with deletion mutants implicate the periplasmic protein LptA, the cytosolic protein LptB, and the IM proteins LptC, LptF, and LptG in the subsequent transport of nascent LPS to the outer membrane (OM), where the LptD/LptE complex flips LPS to the outer surface. PW002059 Metabolic peptidoglycan biosynthesis I 2 Peptidoglycan is a net-like polymer which surrounds the cytoplasmic membrane of most bacteria and functions to maintain cell shape and prevent rupture due to the internal turgor.In E. coli K-12, the peptidoglycan consists of glycan strands of alternating subunits of N-acetylglucosamine (GlcNAc) and N-acetylmuramic acid (MurNAc) which are cross-linked by short peptides. The pathway for constructing this net involves two cell compartments: cytoplasm and periplasmic space. The pathway starts with a beta-D-fructofuranose going through a mannose PTS permease, phosphorylating the compund and producing a beta-D-fructofuranose 6 phosphate. This compound can be obtained from the glycolysis and pyruvate dehydrogenase or from an isomerization reaction of Beta-D-glucose 6-phosphate through a glucose-6-phosphate isomerase.The compound Beta-D-fructofuranose 6 phosphate and L-Glutamine react with a glucosamine fructose-6-phosphate aminotransferase, thus producing a glucosamine 6-phosphate and a l-glutamic acid. The glucosamine 6-phosphate interacts with phosphoglucosamine mutase in a reversible reaction producing glucosamine-1P. Glucosamine-1p and acetyl coa undergo acetylation throuhg a bifunctional protein glmU releasing Coa and a hydrogen ion and producing a N-acetyl-glucosamine 1-phosphate. Glmu, being a bifunctional protein, follows catalyze the interaction of N-acetyl-glucosamine 1-phosphate, hydrogen ion and UTP into UDP-N-acetylglucosamine and pyrophosphate. UDP-N-acetylglucosamine then interacts with phosphoenolpyruvic acid and a UDP-N acetylglucosamine 1- carboxyvinyltransferase realeasing a phosphate and the compound UDP-N-acetyl-alpha-D-glucosamine-enolpyruvate. This compound undergoes a NADPH dependent reduction producing a UDP-N-acetyl-alpha-D-muramate through a UDP-N-acetylenolpyruvoylglucosamine reductase. UDP-N-acetyl-alpha-D-muramate and L-alanine react in an ATP-mediated ligation through a UDP-N-acetylmuramate-alanine ligase releasing an ADP, hydrogen ion, a phosphate and a UDP-N-acetylmuramoyl-L-alanine. This compound interacts with D-glutamic acid and ATP through UDP-N-acetylmuramoylalanine-D-glutamate ligase releasing ADP, A phosphate and UDP-N-acetylmuramoyl-L-alanyl-D-glutamate. The latter compound then interacts with meso-diaminopimelate in an ATP mediated ligation through a UDP-N-acetylmuramoylalanine-D-glutamate-2,6-diaminopimelate ligase resulting in ADP, phosphate, hydrogen ion and UDP-N-Acetylmuramoyl-L-alanyl-D-gamma-glutamyl-meso-2,6-diaminopimelate. This compound in turn with D-alanyl-D-alanine react in an ATP-mediated ligation through UDP-N-Acetylmuramoyl-tripeptide-D-alanyl-D-alanine ligase to produce UDP-N-acetyl-alpha-D-muramoyl-L-alanyl-gama-D-glutamyl-meso-2,6-diaminopimeloyl-Dalanyl-D-alanine and hydrogen ion, ADP, phosphate. UDP-N-acetyl-alpha-D-muramoyl-L-alanyl-gama-D-glutamyl-meso-2,6-diaminopimeloyl-Dalanyl-D-alanine interacts with di-trans,octa-cis-undecaprenyl phosphate through a phospho-N-acetylmuramoyl-pentapeptide-transferase, resulting in UMP and N-Acetylmuramoyl-L-alanyl-D-glutamyl-meso-2,6-diaminopimelyl-D-alanyl-D-alanine-diphosphoundecaprenol which in turn reacts with a UDP-N-acetylglucosamine through a N-acetylglucosaminyl transferase to produce a hydrogen, UDP and Undecaprenyl-diphospho-N-acetylmuramoyl-(N-acetylglucosamine)-L-alanyl-D-glutaminyl-meso-2,6-diaminopimeloyl-D-alanyl-D-alanine. This compound ends the cytoplasmic part of the pathway. Undecaprenyl-diphospho-N-acetylmuramoyl-(N-acetylglucosamine)-L-alanyl-D-glutaminyl-meso-2,6-diaminopimeloyl-D-alanyl-D-alanine is transported through a lipi II flippase. Once in the periplasmic space, the compound reacts with a penicillin binding protein 1A prodducing a peptidoglycan dimer, a hydrogen ion, and UDP. The peptidoglycan dimer then reacts with a penicillin binding protein 1B producing a peptidoglycan with D,D, cross-links and a D-alanine. PW002062 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 trehalose biosynthesis I Under conditions of elevated osmotic strength, E. coli can regulate the osmotic strength of the cytoplasm by accumulating K+ ions and some organic molecules, commonly called osmoprotectants or compatible solutes. The preferred osmoprotectant of E. coli is glycine betaine. However, its synthesis relies on an external supply of proline, betaines, or choline. When these compounds are not available, a cell can achieve a moderate level of osmotic tolerance by accumulation of glutamate and trehalose. E. coli synthesizes and accumulates trehalose when exposed to osmotic stress and low temperatures. It is synthesized from UDP-glucose and glucose-6-phosphate via trehalose-6-phosphate, by the action of two enzymes, trehalose-6-phosphate synthase and trehalose-6-phosphate phosphatase. Expression of both genes encoding the two enzymes, otsA and otsB, is osmotically regulated. Transcription from these genes increases during osmotic stress and cold shock and when the cells enter stationary phase, and requires the stress sigma factor RpoS. Synthesis of trehalose is also stimulated directly by K+ ion-dependent activation of trehalose-6-phosphate synthase enzyme. Under osmotic stress, E. coli overproduces trehalose, some of which is excreted to the periplasmic space. Once there, it is degraded by the periplasmic trehalase. This process was named "a futile cycle for controlling the cytoplasmic level of trehalose". (EcoCyc) PW002088 Metabolic superpathway of (KDO)<SUB>2</SUB>-lipid A biosynthesis NAGLIPASYN-PWY pyrimidine deoxyribonucleotides <i>de novo</i> biosynthesis I PWY0-166 pyrimidine ribonucleotides interconversion PWY-5687-1 polymyxin resistance PWY0-1338 enterobacterial common antigen biosynthesis ECASYN-PWY peptidoglycan biosynthesis I (<I>meso</I>-diaminopimelate containing) PEPTIDOGLYCANSYN-PWY Lipid A-core biosynthesis LIPA-CORESYN-PWY trehalose biosynthesis I TRESYN-PWY Specdb::CMs 22299 Specdb::CMs 37408 Specdb::CMs 149344 Specdb::CMs 1057272 Specdb::CMs 1057275 Specdb::CMs 1057277 Specdb::CMs 1057279 Specdb::CMs 1057281 Specdb::CMs 1057282 Specdb::CMs 1057284 Specdb::CMs 1057286 Specdb::CMs 1057288 Specdb::CMs 1057290 Specdb::CMs 1057292 Specdb::CMs 1057293 Specdb::CMs 1057295 Specdb::CMs 1057296 Specdb::CMs 1057298 Specdb::CMs 1057301 Specdb::CMs 1057303 Specdb::CMs 1057305 Specdb::CMs 1057307 Specdb::CMs 1057308 Specdb::CMs 1057310 Specdb::CMs 1057312 Specdb::NmrOneD 1318 Specdb::NmrOneD 4834 Specdb::NmrOneD 4835 Specdb::NmrOneD 143390 Specdb::NmrOneD 143391 Specdb::NmrOneD 143392 Specdb::NmrOneD 143393 Specdb::NmrOneD 143394 Specdb::NmrOneD 143395 Specdb::NmrOneD 143396 Specdb::NmrOneD 143397 Specdb::NmrOneD 143398 Specdb::NmrOneD 143399 Specdb::NmrOneD 143400 Specdb::NmrOneD 143401 Specdb::NmrOneD 143402 Specdb::NmrOneD 143403 Specdb::NmrOneD 143404 Specdb::NmrOneD 143405 Specdb::NmrOneD 143406 Specdb::NmrOneD 143407 Specdb::NmrOneD 143408 Specdb::NmrOneD 143409 Specdb::MsMs 501 Specdb::MsMs 502 Specdb::MsMs 503 Specdb::MsMs 3932 Specdb::MsMs 179256 Specdb::MsMs 179257 Specdb::MsMs 179258 Specdb::MsMs 181581 Specdb::MsMs 181582 Specdb::MsMs 181583 Specdb::MsMs 439115 Specdb::MsMs 2253196 Specdb::MsMs 2253283 Specdb::MsMs 2255259 Specdb::MsMs 2255294 Specdb::MsMs 2257370 Specdb::MsMs 2259177 Specdb::MsMs 2259374 Specdb::MsMs 2286802 Specdb::MsMs 2286803 Specdb::MsMs 2286804 Specdb::MsMs 3082461 Specdb::MsMs 3082462 Specdb::MsMs 3082463 Specdb::NmrTwoD 1260 HMDB00295 6031 5809 C00015 17659 UDP UDP UDP 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 Bennett, B. D., Kimball, E. H., Gao, M., Osterhout, R., Van Dien, S. J., Rabinowitz, J. D. (2009). "Absolute metabolite concentrations and implied enzyme active site occupancy in Escherichia coli." Nat Chem Biol 5:593-599. 19561621 Ishii, N., Nakahigashi, K., Baba, T., Robert, M., Soga, T., Kanai, A., Hirasawa, T., Naba, M., Hirai, K., Hoque, A., Ho, P. Y., Kakazu, Y., Sugawara, K., Igarashi, S., Harada, S., Masuda, T., Sugiyama, N., Togashi, T., Hasegawa, M., Takai, Y., Yugi, K., Arakawa, K., Iwata, N., Toya, Y., Nakayama, Y., Nishioka, T., Shimizu, K., Mori, H., Tomita, M. (2007). "Multiple high-throughput analyses monitor the response of E. coli to perturbations." Science 316:593-597. 17379776 Rise, A. (1976). "[Drugs and the fetus]." Tidsskr Nor Laegeforen 96:41-42. 1257952 Morrone, F. B., Jacques-Silva, M. C., Horn, A. P., Bernardi, A., Schwartsmann, G., Rodnight, R., Lenz, G. (2003). "Extracellular nucleotides and nucleosides induce proliferation and increase nucleoside transport in human glioma cell lines." J Neurooncol 64:211-218. 14558596 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 Brouwer A, Morse DC, Lans MC, Schuur AG, Murk AJ, Klasson-Wehler E, Bergman A, Visser TJ: Interactions of persistent environmental organohalogens with the thyroid hormone system: mechanisms and possible consequences for animal and human health. Toxicol Ind Health. 1998 Jan-Apr;14(1-2):59-84. 9460170 Kamisako T, Kobayashi Y, Takeuchi K, Ishihara T, Higuchi K, Tanaka Y, Gabazza EC, Adachi Y: Recent advances in bilirubin metabolism research: the molecular mechanism of hepatocyte bilirubin transport and its clinical relevance. J Gastroenterol. 2000;35(9):659-64. 11023036 Syme MR, Paxton JW, Keelan JA: Drug transfer and metabolism by the human placenta. Clin Pharmacokinet. 2004;43(8):487-514. 15170365 Collier AC, Tingle MD, Paxton JW, Mitchell MD, Keelan JA: Metabolizing enzyme localization and activities in the first trimester human placenta: the effect of maternal and gestational age, smoking and alcohol consumption. Hum Reprod. 2002 Oct;17(10):2564-72. 12351530 Zeng, Bin; Rao, Linfan; Li, Gaowo. Method for manufacturing uridine diphosphate. Faming Zhuanli Shenqing Gongkai Shuomingshu (2007), 14pp. http://hmdb.ca/system/metabolites/msds/000/000/216/original/HMDB00295.pdf?1358463373 Ribonucleoside-diphosphate reductase 1 subunit alpha P00452 RIR1_ECOLI nrdA http://ecmdb.ca/proteins/P00452.xml Polyribonucleotide nucleotidyltransferase P05055 PNP_ECOLI pnp http://ecmdb.ca/proteins/P05055.xml 6-phosphofructokinase isozyme 2 P06999 K6PF2_ECOLI pfkB http://ecmdb.ca/proteins/P06999.xml Cytidylate kinase P0A6I0 KCY_ECOLI cmk http://ecmdb.ca/proteins/P0A6I0.xml Nucleoside diphosphate kinase P0A763 NDK_ECOLI ndk http://ecmdb.ca/proteins/P0A763.xml 6-phosphofructokinase isozyme 1 P0A796 K6PF1_ECOLI pfkA http://ecmdb.ca/proteins/P0A796.xml Uridylate kinase P0A7E9 PYRH_ECOLI pyrH http://ecmdb.ca/proteins/P0A7E9.xml Uridine kinase P0A8F4 URK_ECOLI udk http://ecmdb.ca/proteins/P0A8F4.xml Thioredoxin-2 P0AGG4 THIO2_ECOLI trxC http://ecmdb.ca/proteins/P0AGG4.xml Lipid-A-disaccharide synthase P10441 LPXB_ECOLI lpxB http://ecmdb.ca/proteins/P10441.xml UDP-N-acetylglucosamine--N-acetylmuramyl-(pentapeptide) pyrophosphoryl-undecaprenol N-acetylglucosamine transferase P17443 MURG_ECOLI murG http://ecmdb.ca/proteins/P17443.xml Lipopolysaccharide 1,2-glucosyltransferase P27129 RFAJ_ECOLI rfaJ http://ecmdb.ca/proteins/P27129.xml UDP-N-acetylglucosamine 2-epimerase P27828 WECB_ECOLI wecB http://ecmdb.ca/proteins/P27828.xml Anaerobic ribonucleoside-triphosphate reductase P28903 NRDD_ECOLI nrdD http://ecmdb.ca/proteins/P28903.xml Alpha,alpha-trehalose-phosphate synthase [UDP-forming] P31677 OTSA_ECOLI otsA http://ecmdb.ca/proteins/P31677.xml Ribonucleoside-diphosphate reductase 2 subunit beta P37146 RIR4_ECOLI nrdF http://ecmdb.ca/proteins/P37146.xml Cellulose synthase catalytic subunit [UDP-forming] P37653 BCSA_ECOLI bcsA http://ecmdb.ca/proteins/P37653.xml Ribonucleoside-diphosphate reductase 2 subunit alpha P39452 RIR3_ECOLI nrdE http://ecmdb.ca/proteins/P39452.xml Adenylate kinase P69441 KAD_ECOLI adk http://ecmdb.ca/proteins/P69441.xml Ribonucleoside-diphosphate reductase 1 subunit beta P69924 RIR2_ECOLI nrdB http://ecmdb.ca/proteins/P69924.xml Undecaprenyl-phosphate 4-deoxy-4-formamido-L-arabinose transferase P77757 ARNC_ECOLI arnC http://ecmdb.ca/proteins/P77757.xml Lipopolysaccharide core biosynthesis protein rfaG P25740 RFAG_ECOLI rfaG http://ecmdb.ca/proteins/P25740.xml Lipopolysaccharide 1,2-N-acetylglucosaminetransferase P27242 WAAU_ECOLI waaU http://ecmdb.ca/proteins/P27242.xml Lipopolysaccharide 1,6-galactosyltransferase P27127 RFAB_ECOLI rfaB http://ecmdb.ca/proteins/P27127.xml Uncharacterized protein yefI P37751 YEFI_ECOLI yefI http://ecmdb.ca/proteins/P37751.xml Glutaredoxin-4 P0AC69 GLRX4_ECOLI grxD http://ecmdb.ca/proteins/P0AC69.xml Glutaredoxin-3 P0AC62 GLRX3_ECOLI grxC http://ecmdb.ca/proteins/P0AC62.xml Probable UDP-N-acetyl-D-mannosaminuronic acid transferase P27836 WECG_ECOLI wecG http://ecmdb.ca/proteins/P27836.xml Uncharacterized protein yefG P37749 YEFG_ECOLI yefG http://ecmdb.ca/proteins/P37749.xml Glutaredoxin-2 P0AC59 GLRX2_ECOLI grxB http://ecmdb.ca/proteins/P0AC59.xml Glutaredoxin-1 P68688 GLRX1_ECOLI grxA http://ecmdb.ca/proteins/P68688.xml Thioredoxin-1 P0AA25 THIO_ECOLI trxA http://ecmdb.ca/proteins/P0AA25.xml Lipopolysaccharide 1,3-galactosyltransferase P27128 RFAI_ECOLI rfaI http://ecmdb.ca/proteins/P27128.xml Nucleoside diphosphate kinase P0A763 NDK_ECOLI ndk http://ecmdb.ca/proteins/P0A763.xml Reduced Thioredoxin + Uridine 5'-diphosphate > dUDP + Water + Oxidized Thioredoxin glutaredoxin + Uridine 5'-diphosphate > dUDP + glutaredoxin + Water Adenosine triphosphate + Uridine 5'-diphosphate <> ADP + Uridine triphosphate R00156 UDPKIN-RXN Adenosine triphosphate + Uridine 5'-monophosphate <> ADP + Uridine 5'-diphosphate R00158 2.7.4.22-RXN Uridine diphosphate-N-acetylglucosamine + Undecaprenyl-diphospho-N-acetylmuramoyl-L-alanyl-D-glutamyl-meso-2,6-diaminopimeloyl-D-alanyl-D-alanine > Hydrogen ion + Undecaprenyl-diphospho-N-acetylmuramoyl-(N-acetylglucosamine)-L-alanyl-D-glutamyl-meso-2,6-diaminopimeloyl-D-alanyl-D-alanine + Uridine 5'-diphosphate R05032 2,3-Bis(3-hydroxytetradecanoyl)-beta-D-glucosaminyl 1-phosphate + UDP-2,3-Bis(3-hydroxytetradecanoyl)glucosamine <> Hydrogen ion + 2,3,2',3'-Tetrakis(3-hydroxytetradecanoyl)-D-glucosaminyl-1,6-beta-D-glucosamine 1-phosphate + Uridine 5'-diphosphate R04606 LIPIDADISACCHARIDESYNTH-RXN Glucose 6-phosphate + UDP-Glucose > Hydrogen ion + Trehalose 6-phosphate + Uridine 5'-diphosphate R02737 O-Acetyl-rhamanosyl-N-acetylglucosamyl-undecaprenyl diphosphate + UDP-Glucose > Glucosyl-O-acetyl-rhamanosyl-N-acetylglucosamyl-undecaprenyl diphosphate + Hydrogen ion + Uridine 5'-diphosphate Glucosyl-O-acetyl-rhamanosyl-N-acetylglucosamyl-undecaprenyl diphosphate + UDP-D-Galacto-1,4-furanose > Galactofuranosyl-glucosyl-O-acetyl-rhamanosyl-N-acetylglucosamyl-undecaprenyl diphosphate + Hydrogen ion + Uridine 5'-diphosphate Undecaprenyl phosphate + Uridine 5''-diphospho-{beta}-4-deoxy-4-formamido-L-arabinose > Undecaprenyl phosphate-4-amino-4-formyl-L-arabinose + Uridine 5'-diphosphate glucosyl-galactosyl-glucosyl-inner core oligosaccharide lipid A + UDP-Glucose > glucosyl-glucosyl-galactosyl-glucosyl-inner core oligosaccharide lipid A + Hydrogen ion + Uridine 5'-diphosphate galactosyl-glucosyl-inner core oligosaccharide lipid A + UDP-Glucose > glucosyl-galactosyl-glucosyl-inner core oligosaccharide lipid A + Hydrogen ion + Uridine 5'-diphosphate glucosyl-inner core oligosaccharide lipid A + UDP-Glucose > galactosyl-glucosyl-inner core oligosaccharide lipid A + Hydrogen ion + Uridine 5'-diphosphate inner core oligosaccharide lipid A (E coli) + UDP-Glucose > glucosyl-inner core oligosaccharide lipid A + Hydrogen ion + Uridine 5'-diphosphate UDP-N-Acetyl-D-mannosaminouronate + Undecaprenyl-N-acetyl-alpha-D-glucosaminyl-pyrophosphate > Hydrogen ion + Uridine 5'-diphosphate + Undecaprenyl-diphospho-N-acetylglucosamine-N-acetylmannosaminuronate Uridine diphosphate-N-acetylglucosamine + Water <> N-Acetylmannosamine + Uridine 5'-diphosphate R00414 RNA + Phosphate <> RNA + Uridine 5'-diphosphate R00438 Uridine triphosphate + Cytidine <> Uridine 5'-diphosphate + Cytidine monophosphate R00516 Uridine triphosphate + Uridine <> Uridine 5'-diphosphate + Uridine 5'-monophosphate R00967 UDP-Glucose + LPS (1-O-antigen) <> Uridine 5'-diphosphate + D-Glucosyllipopolysaccharide R01994 dUDP + Thioredoxin disulfide + Water <> Thioredoxin + Uridine 5'-diphosphate R02018 UDP-Glucose + Glucose 6-phosphate <> Uridine 5'-diphosphate + Trehalose 6-phosphate R02737 UDP-Glucose + Cellulose <> Uridine 5'-diphosphate + Cellulose R02889 Uridine triphosphate + D-Tagatose 6-phosphate <> Uridine 5'-diphosphate + D-Tagatose 1,6-bisphosphate R03238 UDP-2,3-Bis(3-hydroxytetradecanoyl)glucosamine + 2,3-Bis(3-hydroxytetradecanoyl)-beta-D-glucosaminyl 1-phosphate <> Uridine 5'-diphosphate + 2,3,2',3'-Tetrakis(3-hydroxytetradecanoyl)-D-glucosaminyl-1,6-beta-D-glucosamine 1-phosphate R04606 Undecaprenyl-diphospho-N-acetylmuramoyl-L-alanyl-D-glutamyl-meso-2,6-diaminopimeloyl-D-alanyl-D-alanine + Uridine diphosphate-N-acetylglucosamine <> Undecaprenyl-diphospho-N-acetylmuramoyl-(N-acetylglucosamine)-L-alanyl-D-glutamyl-meso-2,6-diaminopimeloyl-D-alanyl-D-alanine + Uridine 5'-diphosphate R05032 MurAc(oyl-L-Ala-D-gamma-Glu-L-Lys-D-Ala-D-Ala)-diphospho-undecaprenol + Uridine diphosphate-N-acetylglucosamine <> Undecaprenyl-diphospho-N-acetylmuramoyl-(N-acetylglucosamine)-L-alanyl-gamma-D-glutamyl-L-lysyl-D-alanyl-D-alanine + Uridine 5'-diphosphate R05662 Uridine 5''-diphospho-{beta}-4-deoxy-4-formamido-L-arabinose + Di-trans,poly-cis-undecaprenyl phosphate <> Undecaprenyl phosphate alpha-L-Ara4FN + Uridine 5'-diphosphate + 4-Amino-4-deoxy-alpha-L-arabinopyranosyl di-trans,octa-cis-undecaprenyl phosphate R07661 Uridine diphosphate-N-acetylglucosamine poly-&beta;-1,6-N-acetyl-D-glucosamine + Uridine 5'-diphosphate RXN0-5413 a lipopolysaccharide + Uridine diphosphate-N-acetylglucosamine a <i>N</i>-acetyl-D-glucosaminyl-lipopolysaccharide + Uridine 5'-diphosphate 2.4.1.56-RXN UDP-Glucose + a lipopolysaccharide D-glucosyl-lipopolysaccharide + Uridine 5'-diphosphate 2.4.1.58-RXN 2,3-Bis(3-hydroxytetradecanoyl)-beta-D-glucosaminyl 1-phosphate + UDP-2,3-Bis(3-hydroxytetradecanoyl)glucosamine > Hydrogen ion + 2,3,2',3'-Tetrakis(3-hydroxytetradecanoyl)-D-glucosaminyl-1,6-beta-D-glucosamine 1-phosphate + Uridine 5'-diphosphate R04606 LIPIDADISACCHARIDESYNTH-RXN N-Acetylmuramoyl-L-alanyl-D-glutamyl-meso-2,6-diaminopimelyl-D-alanyl-D-alanine-diphosphoundecaprenol + Uridine diphosphate-N-acetylglucosamine <> Hydrogen ion + N-Acetylmuramoyl-L-alanyl-D-glutamyl-L-lysyl-D-alanyl-D-alanine-diphosphoundecaprenyl-N-acetylglucosamine + Uridine 5'-diphosphate NACGLCTRANS-RXN Uridine 5'-diphosphate + Water > Phosphate + Uridine 5'-monophosphate + Hydrogen ion RXN-12197 Uridine 5''-diphospho-{beta}-4-deoxy-4-formamido-L-arabinose + Di-trans,poly-cis-undecaprenyl phosphate > 4-deoxy-4-formamido-&alpha;-L-arabinopyranosyl <i>ditrans,octacis</i>-undecaprenyl phosphate + Uridine 5'-diphosphate RXN0-3521 UDP-Glucose + Heptosyl2-KDO2-lipid A > Hydrogen ion + Glucosyl-heptosyl2-KDO2-lipid A + Uridine 5'-diphosphate RXN0-5120 Glucosyl-heptosyl3-KDO2-lipid A-bisphosphate + Uridine diphosphategalactose > Hydrogen ion + Galactosyl-glucosyl-heptosyl3-KDO2-lipid A-bisphosphate + Uridine 5'-diphosphate RXN0-5124 UDP-Glucose + Galactosyl-glucosyl-heptosyl3-KDO2-lipid A-bisphosphate > Hydrogen ion + Galactosyl-glucosyl2-heptosyl3-KDO2-lipid A-bisphosphate + Uridine 5'-diphosphate RXN0-5125 UDP-Glucose + Galactosyl-glucosyl2-heptosyl3-KDO2-lipid A-bisphosphate > Hydrogen ion + Galactosyl-glucosyl3-heptosyl3-KDO2-lipid A-bisphosphate + Uridine 5'-diphosphate RXN0-5126 octyl alpha-D-glucopyranoside + UDP-D-Galacto-1,4-furanose Hydrogen ion + octyl beta-1,6-D-galactofuranosyl-alpha-D-glucopyranoside + Uridine 5'-diphosphate RXN0-5210 UDP-Glucose + &alpha;-D-glucose 6-phosphate > Hydrogen ion + Uridine 5'-diphosphate + Trehalose 6-phosphate TREHALOSE6PSYN-RXN Uridine 5'-diphosphate + Adenosine triphosphate > Uridine triphosphate + ADP UDPKIN-RXN Undecaprenyl-N-acetyl-alpha-D-glucosaminyl-pyrophosphate + UDP-N-Acetyl-D-mannosaminouronate <> Hydrogen ion + Undecaprenyl phosphate + Uridine 5'-diphosphate UDPMANACATRANS-RXN UDP-4-Deoxy-4-formamido-beta-L-arabinose + di-trans,octa-cis-undecaprenyl phosphate > Uridine 5'-diphosphate + 4-deoxy-4-formamido-alpha-L-arabinose di-trans,octa-cis-undecaprenyl phosphate UDP-Glucose + (1,4-beta-D-glucosyl)(n) > Uridine 5'-diphosphate + (1,4-beta-D-glucosyl)(n+1) UDP-2,3-Bis(3-hydroxytetradecanoyl)glucosamine + 2,3-bis((3R)-3-hydroxymyristoyl)-beta-D-glucosaminyl 1-phosphate > Uridine 5'-diphosphate + 2,3-bis(3-Hydroxytetradecanoyl)-D-glucosaminyl-1,6-beta-D-2,3-bis(3-hydroxytetradecanoyl)-beta-D-glucosaminyl 1-phosphate Uridine diphosphate-N-acetylglucosamine + Mur2Ac(oyl-L-Ala-gamma-D-Glu-L-Lys-D-Ala-D-Ala)-diphosphoundecaprenol > Uridine 5'-diphosphate + GlcNAc-(1->4)-Mur2Ac(oyl-L-Ala-gamma-D-Glu-L-Lys-D-Ala-D-Ala)-diphosphoundecaprenol UDP-Glucose + Glucose 6-phosphate > Uridine 5'-diphosphate + Trehalose 6-phosphate Adenosine triphosphate + Uridine 5'-monophosphate > ADP + Uridine 5'-diphosphate Uridine diphosphategalactose + LPS (1-O-antigen) > Uridine 5'-diphosphate + 3-alpha-D-galactosyl-[lipopolysaccharide glucose] UDP-Glucose + LPS (1-O-antigen) > Uridine 5'-diphosphate + D-glucosyl-lipopolysaccharide Uridine diphosphate-N-acetylglucosamine + LPS (1-O-antigen) > Uridine 5'-diphosphate + N-acetyl-D-glucosaminyllipopolysaccharide UDP-ManNAcA + Und-PP-GlcNAc > Uridine 5'-diphosphate + Und-PP-GlcNAc-ManNAcA Uridine diphosphate-N-acetylglucosamine + Mur2Ac(oyl-L-Ala-gamma-D-Glu-L-Lys-D-Ala-D-Ala)-diphosphoundecaprenol <> Uridine 5'-diphosphate + Undecaprenyl-diphospho-N-acetylmuramoyl-(N-acetylglucosamine)-L-alanyl-gamma-D-glutamyl-L-lysyl-D-alanyl-D-alanine R05662 R06173 Adenosine triphosphate + dCMP + Uridine 5'-monophosphate <> ADP + dCDP + Uridine 5'-diphosphate R00512 R01665 N-Acetyl-D-glucosaminyldiphospho-di-trans,octa-cis-undecaprenol <> Uridine 5'-diphosphate R04477 UDP-Glucose <> Uridine 5'-diphosphate R02889 R06023 Uridine diphosphate-N-acetylglucosamine + LPS (1-O-antigen) <> Uridine 5'-diphosphate R01996 Uridine diphosphategalactose + LPS (1-O-antigen) <> Uridine 5'-diphosphate + 3-alpha-D-Galactosyl-[lipopolysaccharide glucose] R01997 2,3-bis[(3R)-3-hydroxymyristoyl]-α-D-glucosaminyl 1-phosphate + UDP-2-N,3-O-bis[(3R)-3-hydroxytetradecanoyl]-α-D-glucosamine > Uridine 5'-diphosphate + Hydrogen ion + (2-N,3-O-bis(3-hydroxytetradecanoyl)-beta-D-glucosaminyl)-(1->6)-(2-N,3-O-bis(3-hydroxytetradecanoyl)-beta-D-glucosaminyl phosphate) PW_R003028 (heptosyl)2-Kdo2-lipid A + UDP-Glucose > Uridine 5'-diphosphate + Hydrogen ion + glucosyl-(heptosyl)2-Kdo2-lipid A PW_R003040 glucosyl-(heptosyl)3-Kdo2-lipid A-bisphosphate + UDP-α-D-galactose > galactosyl-glucosyl-(heptosyl)3-Kdo2-lipid A-bisphosphate + Uridine 5'-diphosphate + Hydrogen ion PW_R003044 galactosyl-glucosyl-(heptosyl)3-Kdo2-lipid A-bisphosphate + UDP-Glucose > Uridine 5'-diphosphate + Hydrogen ion + galactosyl-(glucosyl)2-(heptosyl)3-Kdo2-lipid A-bisphosphate PW_R003045 galactosyl-(glucosyl)2-(heptosyl)3-Kdo2-lipid A-bisphosphate + UDP-Glucose > Uridine 5'-diphosphate + Hydrogen ion + galactosyl-(glucosyl)3-(heptosyl)3-Kdo2-lipid A-bisphosphate PW_R003046 UDP-4-Deoxy-4-formamido-beta-L-arabinose + di-trans,octa-cis-undecaprenyl phosphate > Uridine 5'-diphosphate + 4-deoxy-4-formamido-α-L-arabinopyranosyl ditrans,octacis-undecaprenyl phosphate PW_R003359 Uridine 5'-diphosphate + Adenosine triphosphate + Uridine 5'-diphosphate > Uridine triphosphate + Adenosine diphosphate + Uridine triphosphate + ADP PW_R003532 Uridine 5'-diphosphate + reduced thioredoxin + Uridine 5'-diphosphate oxidized thioredoxin + Water + dUDP + dUDP PW_R003537 Undecaprenyl-diphospho-N-acetylmuramoyl-L-alanyl-D-glutamyl-meso-2,6-diaminopimeloyl-D-alanyl-D-alanine + Uridine diphosphate-N-acetylglucosamine + Undecaprenyl-diphospho-N-acetylmuramoyl-L-alanyl-D-glutamyl-meso-2,6-diaminopimeloyl-D-alanyl-D-alanine > Uridine 5'-diphosphate + Hydrogen ion + lipid II(A) + Uridine 5'-diphosphate PW_R003453 UDP-Glucose + Alpha-D-glucose 6-phosphate > Uridine 5'-diphosphate + Trehalose 6-phosphate + Hydrogen ion + Uridine 5'-diphosphate PW_R003513 Uridine 5'-monophosphate + Adenosine triphosphate > Adenosine diphosphate + Uridine 5'-diphosphate + ADP + Uridine 5'-diphosphate PW_R003531 N-acetyl-α-D-glucosaminyl-diphospho-ditrans,octacis-undecaprenol + UDP-ManNAcA > Uridine 5'-diphosphate + Hydrogen ion + Undecaprenyl N-acetyl-glucosaminyl-N-acetyl-mannosaminuronate pyrophosphate + Uridine 5'-diphosphate + Undecaprenyl-diphospho-N-acetylglucosamine-N-acetylmannosaminuronate PW_R003701 N-Acetylmuramoyl-L-alanyl-D-glutamyl-meso-2,6-diaminopimelyl-D-alanyl-D-alanine-diphosphoundecaprenol + Uridine diphosphate-N-acetylglucosamine > Undecaprenyl-diphospho-N-acetylmuramoyl-(N-acetylglucosamine)-L-alanyl-D-glutaminyl-meso-2,6-diaminopimeloyl-D-alanyl-D-alanine + Uridine 5'-diphosphate + Hydrogen ion PW_R006016 Undecaprenyl-N-acetyl-alpha-D-glucosaminyl-pyrophosphate + UDP-ManNAcA > Uridine 5'-diphosphate + Undecaprenyl-diphospho-N-acetylglucosamine-N-acetylmannosaminuronate + Hydrogen ion PW_R005973 UDP-Glucose + Mannose 6-phosphate > alpha,alpha-Trehalose 6-phosphate + Uridine 5'-diphosphate + Hydrogen ion PW_R006093 Adenosine triphosphate + Uridine 5'-monophosphate <> ADP + Uridine 5'-diphosphate 2 2,3-Bis(3-hydroxytetradecanoyl)-beta-D-glucosaminyl 1-phosphate + UDP-2,3-Bis(3-hydroxytetradecanoyl)glucosamine <> Hydrogen ion +2 2,3,2',3'-Tetrakis(3-hydroxytetradecanoyl)-D-glucosaminyl-1,6-beta-D-glucosamine 1-phosphate + Uridine 5'-diphosphate Adenosine triphosphate + Uridine 5'-diphosphate <> ADP + Uridine triphosphate 2 2,3-Bis(3-hydroxytetradecanoyl)-beta-D-glucosaminyl 1-phosphate + UDP-2,3-Bis(3-hydroxytetradecanoyl)glucosamine <> Hydrogen ion +2 2,3,2',3'-Tetrakis(3-hydroxytetradecanoyl)-D-glucosaminyl-1,6-beta-D-glucosamine 1-phosphate + Uridine 5'-diphosphate Adenosine triphosphate + Uridine 5'-diphosphate <> ADP + Uridine triphosphate Gutnick minimal complete medium (4.7 g/L KH2PO4; 13.5 g/L K2HPO4; 1 g/L K2SO4; 0.1 g/L MgSO4-7H2O; 10 mM NH4Cl) with 4 g/L glucose Shake flask and filter culture 1790.0 uM 0.0 37 oC K12 NCM3722 Mid-Log Phase 7160000 0 Bennett, B. D., Kimball, E. H., Gao, M., Osterhout, R., Van Dien, S. J., Rabinowitz, J. D. (2009). "Absolute metabolite concentrations and implied enzyme active site occupancy in Escherichia coli." Nat Chem Biol 5:593-599. 19561621 48 mM Na2HPO4, 22 mM KH2PO4, 10 mM NaCl, 45 mM (NH4)2SO4, supplemented with 1 mM MgSO4, 1 mg/l thiamine·HCl, 5.6 mg/l CaCl2, 8 mg/l FeCl3, 1 mg/l MnCl2·4H2O, 1.7 mg/l ZnCl2, 0.43 mg/l CuCl2·2H2O, 0.6 mg/l CoCl2·2H2O and 0.6 mg/l Na2MoO4·2H2O. 4 g/L Gluco Bioreactor, pH controlled, O2 and CO2 controlled, dilution rate: 0.2/h 386.0 uM 0.0 37 oC BW25113 Stationary Phase, glucose limited 1544000 0 Ishii, N., Nakahigashi, K., Baba, T., Robert, M., Soga, T., Kanai, A., Hirasawa, T., Naba, M., Hirai, K., Hoque, A., Ho, P. Y., Kakazu, Y., Sugawara, K., Igarashi, S., Harada, S., Masuda, T., Sugiyama, N., Togashi, T., Hasegawa, M., Takai, Y., Yugi, K., Arakawa, K., Iwata, N., Toya, Y., Nakayama, Y., Nishioka, T., Shimizu, K., Mori, H., Tomita, M. (2007). "Multiple high-throughput analyses monitor the response of E. coli to perturbations." Science 316:593-597. 17379776