2.02012-05-31 14:07:18 -06002015-09-13 12:56:14 -0600ECMDB04171M2MDB000651UDP-GlucoseUDP-glucose is key intermediate in carbohydrate metabolism. Serves as a precursor of glycogen, can be metabolized into UDPgalactose and UDPglucuronic acid which can then be incorporated into polysaccharides as galactose and glucuronic acid. Also serves as a precursor of lipopolysaccharides.(UDP)glucose(UPD)-glucoseGDP-GlcUDP GlucoseUDP-a-D-GlucoseUDP-a-delta-GlucoseUDP-a-δ-GlucoseUDP-alpha-D-GlucoseUDP-alpha-delta-GlucoseUDP-D-GlucoseUDP-delta-GlucoseUDP-GlcUDP-GlucoseUDP-α-D-GlucoseUDP-α-δ-GlucoseUDP-δ-GlucoseUDPGUDPglucoseUridine 5'-diphosphate glucoseUridine 5'-diphospho-a-D-glucoseUridine 5'-diphospho-a-delta-glucoseUridine 5'-diphospho-a-δ-glucoseUridine 5'-diphospho-alpha-D-glucoseUridine 5'-diphospho-alpha-delta-glucoseUridine 5'-diphospho-α-D-glucoseUridine 5'-diphospho-α-δ-glucoseUridine 5'-diphosphoglucoseUridine 5'-diphosphoric acid glucoseUridine 5'-pyrophosphate a-D-glucopyranosyl esterUridine 5'-pyrophosphate a-delta-glucopyranosyl esterUridine 5'-pyrophosphate a-δ-glucopyranosyl esterUridine 5'-pyrophosphoric acid a-D-glucopyranosyl esterUridine 5'-pyrophosphoric acid a-delta-glucopyranosyl esterUridine 5'-pyrophosphoric acid a-δ-glucopyranosyl esterUridine diphosphate-glucoseUridine diphospho-D-glucoseUridine diphospho-delta-glucoseUridine diphospho-δ-glucoseUridine diphosphoglucoseUridine diphosphoric acid-glucoseUridine pyrophosphate-glucoseUridine pyrophosphoric acid-glucoseC15H24N2O17P2566.3018566.055020376[({[(2R,3S,4R,5R)-5-(2,4-dioxo-1,2,3,4-tetrahydropyrimidin-1-yl)-3,4-dihydroxyoxolan-2-yl]methoxy}(hydroxy)phosphoryl)oxy]({[(2R,3R,4S,5S,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl]oxy})phosphinic acidudp-α-D-glucose133-89-1OC[C@@H]1OC(OP(O)(=O)OP(O)(=O)OC[C@@H]2O[C@@H]([C@@H](O)[C@H]2O)N2C=CC(=O)NC2=O)[C@@H](O)[C@H](O)[C@H]1OInChI=1S/C15H24N2O17P2/c18-3-5-8(20)10(22)12(24)14(32-5)33-36(28,29)34-35(26,27)30-4-6-9(21)11(23)13(31-6)17-2-1-7(19)16-15(17)25/h1-2,5-6,8-14,18,20-24H,3-4H2,(H,26,27)(H,28,29)(H,16,19,25)/t5-,6-,8-,9-,10+,11-,12-,13-,14?/m0/s1HSCJRCZFDFQWRP-LPTOLDDLSA-NSolidCytosolExtra-organismPeriplasmlogp-1.43logs-1.58solubility1.50e+01 g/llogp-5pka_strongest_acidic1.73pka_strongest_basic-3.6iupac[({[(2R,3S,4R,5R)-5-(2,4-dioxo-1,2,3,4-tetrahydropyrimidin-1-yl)-3,4-dihydroxyoxolan-2-yl]methoxy}(hydroxy)phosphoryl)oxy]({[(2R,3R,4S,5S,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl]oxy})phosphinic acidaverage_mass566.3018mono_mass566.055020376smilesOC[C@@H]1OC(OP(O)(=O)OP(O)(=O)OC[C@@H]2O[C@@H]([C@@H](O)[C@H]2O)N2C=CC(=O)NC2=O)[C@@H](O)[C@H](O)[C@H]1OformulaC15H24N2O17P2inchiInChI=1S/C15H24N2O17P2/c18-3-5-8(20)10(22)12(24)14(32-5)33-36(28,29)34-35(26,27)30-4-6-9(21)11(23)13(31-6)17-2-1-7(19)16-15(17)25/h1-2,5-6,8-14,18,20-24H,3-4H2,(H,26,27)(H,28,29)(H,16,19,25)/t5-,6-,8-,9-,10+,11-,12-,13-,14?/m0/s1inchikeyHSCJRCZFDFQWRP-LPTOLDDLSA-Npolar_surface_area291.54refractivity106.46polarizability45.39rotatable_bond_count9acceptor_count14donor_count9physiological_charge-2formal_charge0Pyrimidine metabolismThe 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.PW000942ec00240MetabolicStarch and sucrose metabolismThe 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-phosphatePW000941ec00500MetabolicGalactose metabolismGalactose can be synthesized through two pathways: melibiose degradation involving an alpha galactosidase and lactose degradation involving a beta galactosidase. Melibiose is first transported inside the cell through the melibiose:Li+/Na+/H+ symporter. Once inside the cell, melibiose is degraded through alpha galactosidase into an alpha-D-galactose and a beta-D-glucose. The beta-D-glucose is phosphorylated by a glucokinase to produce a beta-D-glucose-6-phosphate which can spontaneously be turned into a alpha D glucose 6 phosphate. This alpha D-glucose-6-phosphate is metabolized into a glucose -1-phosphate through a phosphoglucomutase-1. The glucose -1-phosphate is transformed into a uridine diphosphate glucose through UTP--glucose-1-phosphate uridylyltransferase. The product, uridine diphosphate glucose, can undergo a reversible reaction in which it can be turned into uridine diphosphategalactose through an UDP-glucose 4-epimerase.
Galactose can also be produced by lactose degradation involving a lactose permease to uptake lactose from the environment and a beta-galactosidase to turn lactose into Beta-D-galactose.
Beta-D-galactose can also be uptaken from the environment through a galactose proton symporter.
Galactose is degraded through the following process:
Beta-D-galactose is introduced into the cytoplasm through a galactose proton symporter, or it can be synthesized from an alpha lactose that is introduced into the cytoplasm through a lactose permease. Alpha lactose interacts with water through a beta-galactosidase resulting in a beta-D-glucose and beta-D-galactose. Beta-D-galactose is isomerized into D-galactose. D-Galactose undergoes phosphorylation through a galactokinase, hence producing galactose 1 phosphate. On the other side of the pathway, a gluose-1-phosphate (product of the interaction of alpha-D-glucose 6-phosphate with a phosphoglucomutase resulting in a alpha-D-glucose-1-phosphate, an isomer of Glucose 1-phosphate, or an isomer of Beta-D-glucose 1-phosphate) interacts with UTP and a hydrogen ion in order to produce a uridine diphosphate glucose. This is followed by the interaction of galactose-1-phosphate with an established amount of uridine diphosphate glucose through a galactose-1-phosphate uridylyltransferase, which in turn output a glucose-1-phosphate and a uridine diphosphate galactose. The glucose -1-phosphate is transformed into a uridine diphosphate glucose through UTP--glucose-1-phosphate uridylyltransferase. The product, uridine diphosphate glucose, can undergo a reversible reaction in which it can be turned into uridine diphosphategalactose through an UDP-glucose 4-epimerase, and so the cycle can keep going as long as more lactose or galactose is imported into the cell
PW000821ec00052MetabolicAscorbate and aldarate metabolismec00053Amino sugar and nucleotide sugar metabolismec00520Pentose and glucuronate interconversionsec00040Lipopolysaccharide biosynthesisE. 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. PW000831ec00540MetabolicGlycerolipid metabolismec00561Metabolic pathwayseco01100Amino sugar and nucleotide sugar metabolism IIThe 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.
The beta-D-fructofuranose 6 -phosphate is isomerized in a reversible reaction into an alpha-D-mannose 6-phosphate. This compound can also be introduced into the cell from the periplasmic space through a mannose PTS permease that phosphorylates an alpha-D-mannose. Alpha-D-mannose 6-phosphate undergoes a reversible reaction through a phosphomannomutase to produce an alpha-D-mannose 1-phosphate.
The alpha-D-mannose 1-phosphate enters the nucleotide sugar metabolism through a reaction with GTP producing a GDP-mannose and releasing a pyrophosphate, all through a mannose-1-phosphate guanylyltransferase. GDP-mannose is then dehydrated to produce GDP-4-dehydro-6-deoxy-alpha-D-mannose through a GDP-mannose 4,6-dehydratase. This compound is then used to synthesize GDP-Beta-L-fucose through a NADPH dependent GDP-L-fucose synthase.
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.PW000887MetabolicAmino sugar and nucleotide sugar metabolism IIIThe 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.PW000895Metaboliccolanic acid building blocks biosynthesisThe 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).
PW000951Metabolicgalactose degradation/Leloir PathwayThe degradation of galactose, also known as Leloir pathway, requires 3 main enzymes once Beta-D-galactose has been converted to galactose through an Aldose-1-epimerase. These are: galactokinase , galactose-1-phosphate uridylyltransferase and UDP-glucose 4-epimerase. Beta-D-galactose can be uptaken from the environment through a galactose proton symporter. It can also be produced by lactose degradation involving a lactose permease to uptake lactose from the environment and a beta-galactosidase to turn lactose into Beta-D-galactose.
Galactose is degraded through the following process:
Beta-D-galactose is introduced into the cytoplasm through a galactose proton symporter, or it can be synthesized from an alpha lactose that is introduced into the cytoplasm through a lactose permease. Alpha lactose interacts with water through a beta-galactosidase resulting in a beta-D-glucose and beta-D-galactose. Beta-D-galactose is isomerized into D-galactose. D-Galactose undergoes phosphorylation through a galactokinase, hence producing galactose 1 phosphate. On the other side of the pathway, a gluose-1-phosphate (product of the interaction of alpha-D-glucose 6-phosphate with a phosphoglucomutase resulting in a alpha-D-glucose-1-phosphate, an isomer of Glucose 1-phosphate, or an isomer of Beta-D-glucose 1-phosphate) interacts with UTP and a hydrogen ion in order to produce a uridine diphosphate glucose. This is followed by the interaction of galactose-1-phosphate with an established amount of uridine diphosphate glucose through a galactose-1-phosphate uridylyltransferase, which in turn output a glucose-1-phosphate and a uridine diphosphate galactose. The glucose -1-phosphate is transformed into a uridine diphosphate glucose through UTP--glucose-1-phosphate uridylyltransferase. The product, uridine diphosphate glucose, can undergo a reversible reaction in which it can be turned into uridine diphosphategalactose through an UDP-glucose 4-epimerase, and so the cycle can keep going as long as more lactose or galactose is imported into the cell.
PW000884Metaboliclipopolysaccharide biosynthesis IIE. 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.PW001905Metaboliclipopolysaccharide biosynthesis IIIE. 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. PW002059Metabolictrehalose biosynthesis IUnder 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)PW002088Metabolicgalactose degradation I (Leloir pathway)GALACTMETAB-PWYcolanic acid building blocks biosynthesisCOLANSYN-PWYLipid A-core biosynthesisLIPA-CORESYN-PWYtrehalose biosynthesis ITRESYN-PWYSpecdb::CMs36799Specdb::CMs48056Specdb::CMs282129Specdb::CMs359703Specdb::CMs359704Specdb::CMs359705Specdb::CMs359706Specdb::CMs359707Specdb::CMs359708Specdb::CMs359709Specdb::CMs359710Specdb::CMs359711Specdb::CMs359712Specdb::CMs359713Specdb::CMs359714Specdb::CMs359715Specdb::CMs359716Specdb::CMs359717Specdb::CMs359718Specdb::CMs359719Specdb::CMs359720Specdb::CMs359721Specdb::CMs359722Specdb::CMs359723Specdb::CMs359724Specdb::NmrOneD5217Specdb::NmrOneD5218Specdb::NmrOneD6422Specdb::NmrOneD6423Specdb::NmrOneD6424Specdb::NmrOneD6425Specdb::NmrOneD6426Specdb::NmrOneD6427Specdb::NmrOneD6428Specdb::NmrOneD6429Specdb::NmrOneD6430Specdb::NmrOneD6431Specdb::NmrOneD6432Specdb::NmrOneD6433Specdb::NmrOneD6434Specdb::NmrOneD6435Specdb::NmrOneD6436Specdb::NmrOneD6437Specdb::NmrOneD6438Specdb::NmrOneD6439Specdb::NmrOneD6440Specdb::NmrOneD6441Specdb::MsMs105438Specdb::MsMs105439Specdb::MsMs105440Specdb::MsMs171927Specdb::MsMs171928Specdb::MsMs171929Specdb::MsMs1448446Specdb::MsMs1448447Specdb::MsMs1448448Specdb::MsMs2227236Specdb::MsMs2227489Specdb::MsMs2229639Specdb::MsMs2229829Specdb::MsMs2232087Specdb::MsMs2232122Specdb::MsMs2407733Specdb::MsMs2407734Specdb::MsMs2407735Specdb::MsMs2531259Specdb::MsMs2531260Specdb::MsMs2531261Specdb::NmrTwoD2043HMDB00286439156C00029UDP-GLUCOSEUridine diphosphate glucoseKeseler, 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-D590.21097882Kanehisa, 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-D114.22080510van 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 370:17-25.17765195Winder, 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 80:2939-2948.18331064Bennett, 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 5:593-599.19561621Ishii, 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 316:593-597.17379776Ohdoi C, Nyhan WL, Kuhara T: Chemical diagnosis of Lesch-Nyhan syndrome using gas chromatography-mass spectrometry detection. J Chromatogr B Analyt Technol Biomed Life Sci. 2003 Jul 15;792(1):123-30.12829005Haugen HF, Skrede S: Nucleotide pyrophosphatase and phosphodiesterase I. Demonstration of activity in normal serum, and an increase in cholestatic liver disease. Scand J Gastroenterol. 1976;11(2):121-7.4880Tarantino G, Morelli L, Califano C: [Uridine diphosphate glucose (UDPG) in the treatment of hepatic disease from chronic alcohol abuse] Riv Eur Sci Med Farmacol. 1990 Apr;12(2):109-17.2080308Schwartz AL, Rall TW: Hormonal regulation of glycogen metabolism in human fetal liver. II. Regulation of glycogen synthase activity. Diabetes. 1975 Dec;24(12):1113-22.811498Hers HG: Mechanisms of blood glucose homeostasis. J Inherit Metab Dis. 1990;13(4):395-410.2122108Raila J, Wirth K, Chen F, Buscher U, Dudenhausen JW, Schweigert FJ: Excretion of vitamin A in urine of women during normal pregnancy and pregnancy complications. Ann Nutr Metab. 2004 Sep-Oct;48(5):357-64. Epub 2004 Nov 9.15542927Ng WG, Xu YK, Kaufman FR, Donnell GN: Deficit of uridine diphosphate galactose in galactosaemia. J Inherit Metab Dis. 1989;12(3):257-66.2515367Marschall HU, Matern H, Wietholtz H, Egestad B, Matern S, Sjovall J: Bile acid N-acetylglucosaminidation. In vivo and in vitro evidence for a selective conjugation reaction of 7 beta-hydroxylated bile acids in humans. J Clin Invest. 1992 Jun;89(6):1981-7.1602004Reynolds TH 4th, Pak Y, Harris TE, Manchester J, Barrett EJ, Lawrence JC Jr: Effects of insulin and transgenic overexpression of UDP-glucose pyrophosphorylase on UDP-glucose and glycogen accumulation in skeletal muscle fibers. J Biol Chem. 2005 Feb 18;280(7):5510-5. Epub 2004 Dec 13.15596435Nielsen JN, Richter EA: Regulation of glycogen synthase in skeletal muscle during exercise. Acta Physiol Scand. 2003 Aug;178(4):309-19.12864735Burma, D. P.; Mortimer, D. C. Biosynthesis of uridine diphosphate glucose and sucrose in sugar-beet leaf. Archives of Biochemistry and Biophysics (1956), 62 16-28.http://hmdb.ca/system/metabolites/msds/000/000/208/original/HMDB00286.pdf?1358463407Protein ushAP07024USHA_ECOLIushAhttp://ecmdb.ca/proteins/P07024.xmlUDP-glucose 4-epimeraseP09147GALE_ECOLIgalEhttp://ecmdb.ca/proteins/P09147.xmlGalactose-1-phosphate uridylyltransferaseP09148GAL7_ECOLIgalThttp://ecmdb.ca/proteins/P09148.xmlUTP--glucose-1-phosphate uridylyltransferaseP0AAB6GALF_ECOLIgalFhttp://ecmdb.ca/proteins/P0AAB6.xmlUTP--glucose-1-phosphate uridylyltransferase_P0AEP3GALU_ECOLIgalUhttp://ecmdb.ca/proteins/P0AEP3.xmlProtein mazGP0AEY3MAZG_ECOLImazGhttp://ecmdb.ca/proteins/P0AEY3.xmlLipopolysaccharide 1,2-glucosyltransferaseP27129RFAJ_ECOLIrfaJhttp://ecmdb.ca/proteins/P27129.xmlAlpha,alpha-trehalose-phosphate synthase [UDP-forming]P31677OTSA_ECOLIotsAhttp://ecmdb.ca/proteins/P31677.xmlCellulose synthase catalytic subunit [UDP-forming]P37653BCSA_ECOLIbcsAhttp://ecmdb.ca/proteins/P37653.xmlPutative sucrose phosphorylaseP76041SUCP_ECOLIycjMhttp://ecmdb.ca/proteins/P76041.xmlUDP-glucose 6-dehydrogenaseP76373UDG_ECOLIugdhttp://ecmdb.ca/proteins/P76373.xmlLipopolysaccharide core biosynthesis protein rfaGP25740RFAG_ECOLIrfaGhttp://ecmdb.ca/proteins/P25740.xmlLipopolysaccharide 1,6-galactosyltransferaseP27127RFAB_ECOLIrfaBhttp://ecmdb.ca/proteins/P27127.xmlUncharacterized protein yefIP37751YEFI_ECOLIyefIhttp://ecmdb.ca/proteins/P37751.xmlLipopolysaccharide 1,3-galactosyltransferaseP27128RFAI_ECOLIrfaIhttp://ecmdb.ca/proteins/P27128.xmlOuter membrane protein NP77747OMPN_ECOLIompNhttp://ecmdb.ca/proteins/P77747.xmlOuter membrane pore protein EP02932PHOE_ECOLIphoEhttp://ecmdb.ca/proteins/P02932.xmlOuter membrane protein FP02931OMPF_ECOLIompFhttp://ecmdb.ca/proteins/P02931.xmlOuter membrane protein CP06996OMPC_ECOLIompChttp://ecmdb.ca/proteins/P06996.xmlWater + UDP-Glucose > Glucose 1-phosphate +2 Hydrogen ion + Uridine 5'-monophosphateR00287Galactose 1-phosphate + UDP-Glucose <> Glucose 1-phosphate + Uridine diphosphategalactoseR00955GALACTURIDYLYLTRANS-RXNUDP-Glucose <> Uridine diphosphategalactoseR00291UDPGLUCEPIM-RXNGlucose 1-phosphate + Hydrogen ion + Uridine triphosphate <> Pyrophosphate + UDP-GlucoseR00289GLUC1PURIDYLTRANS-RXNGlucose 6-phosphate + UDP-Glucose > Hydrogen ion + Trehalose 6-phosphate + Uridine 5'-diphosphateR02737Water + 2 NAD + UDP-Glucose <>3 Hydrogen ion +2 NADH + Uridine diphosphate glucuronic acid + UDP-Glucuronic acidR00286UGD-RXNO-Acetyl-rhamanosyl-N-acetylglucosamyl-undecaprenyl diphosphate + UDP-Glucose > Glucosyl-O-acetyl-rhamanosyl-N-acetylglucosamyl-undecaprenyl diphosphate + Hydrogen ion + Uridine 5'-diphosphateglucosyl-galactosyl-glucosyl-inner core oligosaccharide lipid A + UDP-Glucose > glucosyl-glucosyl-galactosyl-glucosyl-inner core oligosaccharide lipid A + Hydrogen ion + Uridine 5'-diphosphategalactosyl-glucosyl-inner core oligosaccharide lipid A + UDP-Glucose > glucosyl-galactosyl-glucosyl-inner core oligosaccharide lipid A + Hydrogen ion + Uridine 5'-diphosphateglucosyl-inner core oligosaccharide lipid A + UDP-Glucose > galactosyl-glucosyl-inner core oligosaccharide lipid A + Hydrogen ion + Uridine 5'-diphosphateinner core oligosaccharide lipid A (E coli) + UDP-Glucose > glucosyl-inner core oligosaccharide lipid A + Hydrogen ion + Uridine 5'-diphosphateUDP-Glucose + Water + 2 NAD <> Uridine diphosphate glucuronic acid +2 NADH +2 Hydrogen ionR00286UDP-Glucose + Water <> Uridine 5'-monophosphate + Glucose 1-phosphateR00287Uridine triphosphate + Glucose 1-phosphate <> Pyrophosphate + UDP-GlucoseR00289UDP-Glucose + LPS (1-O-antigen) <> Uridine 5'-diphosphate + D-GlucosyllipopolysaccharideR01994UDP-Glucose + Glucose 6-phosphate <> Uridine 5'-diphosphate + Trehalose 6-phosphateR02737UDP-Glucose + Cellulose <> Uridine 5'-diphosphate + CelluloseR02889GDP-L-Fucose + UDP-Glucose + Uridine diphosphate glucuronic acid + Uridine diphosphategalactose colanic acidRXN0-5377UDP-Glucose + a lipopolysaccharide D-glucosyl-lipopolysaccharide + Uridine 5'-diphosphate2.4.1.58-RXNHydrogen ion + Glucose 1-phosphate + Uridine triphosphate > UDP-Glucose + PyrophosphateGLUC1PURIDYLTRANS-RXNUDP-Glucose + Heptosyl2-KDO2-lipid A > Hydrogen ion + Glucosyl-heptosyl2-KDO2-lipid A + Uridine 5'-diphosphateRXN0-5120UDP-Glucose + Galactosyl-glucosyl-heptosyl3-KDO2-lipid A-bisphosphate > Hydrogen ion + Galactosyl-glucosyl2-heptosyl3-KDO2-lipid A-bisphosphate + Uridine 5'-diphosphateRXN0-5125UDP-Glucose + Galactosyl-glucosyl2-heptosyl3-KDO2-lipid A-bisphosphate > Hydrogen ion + Galactosyl-glucosyl3-heptosyl3-KDO2-lipid A-bisphosphate + Uridine 5'-diphosphateRXN0-5126UDP-Glucose + α-D-glucose 6-phosphate > Hydrogen ion + Uridine 5'-diphosphate + Trehalose 6-phosphateTREHALOSE6PSYN-RXNUDP-Glucose + Water + NAD > Hydrogen ion + NADH + Uridine diphosphate glucuronic acidUGD-RXNUDP-Glucose + (1,4-beta-D-glucosyl)(n) > Uridine 5'-diphosphate + (1,4-beta-D-glucosyl)(n+1)UDP-Glucose + Galactose 1-phosphate > Alpha-D-glucose 1-phosphate + Uridine diphosphategalactoseUDP-Glucose > Uridine diphosphategalactoseUridine triphosphate + Alpha-D-glucose 1-phosphate > Pyrophosphate + UDP-GlucoseUDP-Glucose + Glucose 6-phosphate > Uridine 5'-diphosphate + Trehalose 6-phosphateUDP-Glucose + LPS (1-O-antigen) > Uridine 5'-diphosphate + D-glucosyl-lipopolysaccharideUDP-Glucose + 2 NAD + Water > UDP-Glucuronic acid +2 NADHUDP-Glucose <> Uridine 5'-diphosphateR02889 R06023 UDP-Glucose + Di-trans,poly-cis-undecaprenyl phosphate <> Uridine 5'-monophosphate + alpha-D-Glucopyranosyl-diphospho-ditrans,octacis-undecaprenolR09641 Glucose 1-phosphate + Uridine triphosphate + Hydrogen ion + Uridine triphosphate > Pyrophosphate + UDP-GlucosePW_R002948β-D-glucose 1-phosphate + Uridine triphosphate + Hydrogen ion + Uridine triphosphate > UDP-Glucose + PyrophosphatePW_R003353Alpha-D-glucose 1-phosphate + Uridine triphosphate + Hydrogen ion + Uridine triphosphate > Pyrophosphate + UDP-GlucosePW_R003566UDP-Glucose > Uridine diphosphategalactose + Uridine diphosphategalactosePW_R002950Galactose 1-phosphate + UDP-Glucose + Galactose 1-phosphate > Uridine diphosphategalactose + Glucose 1-phosphate + Uridine diphosphategalactosePW_R003296Alpha-D-glucose 1-phosphate + UDP-galactose > UDP-Glucose + Galactose 1-phosphate + Galactose 1-phosphatePW_R003354UDP-Glucose <> Uridine diphosphategalactose + Uridine diphosphategalactosePW_R002951(heptosyl)2-Kdo2-lipid A + UDP-Glucose > Uridine 5'-diphosphate + Hydrogen ion + glucosyl-(heptosyl)2-Kdo2-lipid APW_R003040galactosyl-glucosyl-(heptosyl)3-Kdo2-lipid A-bisphosphate + UDP-Glucose > Uridine 5'-diphosphate + Hydrogen ion + galactosyl-(glucosyl)2-(heptosyl)3-Kdo2-lipid A-bisphosphatePW_R003045galactosyl-(glucosyl)2-(heptosyl)3-Kdo2-lipid A-bisphosphate + UDP-Glucose > Uridine 5'-diphosphate + Hydrogen ion + galactosyl-(glucosyl)3-(heptosyl)3-Kdo2-lipid A-bisphosphatePW_R003046UDP-Glucose + 2 NAD + Water > UDP-Glucuronic acid +2 NADH +3 Hydrogen ionPW_R003355UDP-Glucose + Alpha-D-glucose 6-phosphate > Uridine 5'-diphosphate + Trehalose 6-phosphate + Hydrogen ion + Uridine 5'-diphosphatePW_R003513UDP-Glucose + D-Fructose + D-Fructose <> Sucrose + PhosphatePW_R003518UDP-Glucose + Mannose 6-phosphate > alpha,alpha-Trehalose 6-phosphate + Uridine 5'-diphosphate + Hydrogen ionPW_R006093UDP-Glucose <> Uridine diphosphategalactoseGlucose 1-phosphate + Hydrogen ion + Uridine triphosphate <> Pyrophosphate + UDP-GlucoseUridine triphosphate + Glucose 1-phosphate <> Pyrophosphate + UDP-GlucoseUDP-Glucose <> Uridine diphosphategalactoseGutnick 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 glucoseShake flask and filter culture2500.0uM0.037 oCK12 NCM3722Mid-Log Phase100000000Bennett, 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 5:593-599.19561621Gutnick 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 glycerolShake flask and filter culture1120.0uM0.037 oCK12 NCM3722Mid-Log Phase44800000Bennett, 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 5:593-599.19561621Gutnick 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 acetateShake flask and filter culture553.0uM0.037 oCK12 NCM3722Mid-Log Phase22120000Bennett, 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 5:593-599.1956162148 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 GlucoBioreactor, pH controlled, O2 and CO2 controlled, dilution rate: 0.2/h1910.0uM0.037 oCBW25113Stationary Phase, glucose limited76400000Ishii, 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