2.0 2012-05-31 14:25:03 -0600 2015-06-03 17:19:13 -0600 ECMDB20054 M2MDB000903 2,3-Bis(3-hydroxytetradecanoyl)-beta-D-glucosaminyl 1-phosphate 2,3-bis(3-hydroxytetradecanoyl)-beta-D-glucosaminyl 1-phosphate is a member of the chemical class known as Hexoses. These are monosaccharides in which the sugar unit is a hexose. Lipid X is a diacylglucosamine 1-phosphate bearing beta-hydroxymyristoyl groups at positions 2 and 3. (PMID 2998869) The simplest of these, lipid X, is a derivative of glucosamine-1-phosphate substituted with beta-hydroxymyristoyl moieties at positions 2 and 3. (PMID 6382553) Lipid X (2,3-diacylglucosamine-1-phosphate) is a novel monosaccharide precursor of lipid A that has some of the physiologic activities of endotoxin but little toxicity. Perhaps because lipid X is a subunit of lipid A, lipid X shows a partial pyrogenic effect while also decreasing the pyrogenic activity of complete lipopolysaccharide (LPS). Lipid X is a potential prototype compound for a new type of chemotherapy directed at blocking the harmful effects of LPS during bacterial septicemia. (PMID 3308707) A monosaccharide precursor of Escherichia coli lipid A, designated lipid X, which is a diacylglucosamine 1-phosphate with beta-hydroxymyristoyl groups at positions 2 and 3, was shown to have the ability to induce the production of tumor necrosis factor (TNF)-like tumor-cytotoxic factor by a murine macrophage-like cell line, J774. (PMID 3701065) 2,3-bis(&beta;-hydroxymyristoyl)-&alpha;-D-glucosaminyl 1-phosphate 2,3-Bis(&beta;-hydroxymyristoyl)-&alpha;-D-glucosaminyl 1-phosphoric acid 2,3-bis(3-hydroxymyristoyl)-&alpha;-D-glucosaminyl 1-phosphate 2,3-Bis(3-hydroxymyristoyl)-&alpha;-D-glucosaminyl 1-phosphoric acid 2,3-Bis(3-hydroxymyristoyl)-a-D-glucosaminyl 1-phosphate 2,3-Bis(3-hydroxymyristoyl)-a-D-glucosaminyl 1-phosphoric acid 2,3-Bis(3-hydroxymyristoyl)-alpha-D-glucosaminyl 1-phosphate 2,3-Bis(3-hydroxymyristoyl)-alpha-D-glucosaminyl 1-phosphoric acid 2,3-Bis(3-hydroxymyristoyl)-α-D-glucosaminyl 1-phosphate 2,3-Bis(3-hydroxymyristoyl)-α-D-glucosaminyl 1-phosphoric acid 2,3-bis(3-hydroxytetradecanoyl)-&alpha;-D-glucosaminyl 1-phosphate 2,3-Bis(3-hydroxytetradecanoyl)-&alpha;-D-glucosaminyl 1-phosphoric acid 2,3-Bis(3-hydroxytetradecanoyl)-a-D-glucosaminyl 1-phosphate 2,3-Bis(3-hydroxytetradecanoyl)-a-D-glucosaminyl 1-phosphoric acid 2,3-Bis(3-hydroxytetradecanoyl)-alpha-D-glucosaminyl 1-phosphate 2,3-Bis(3-hydroxytetradecanoyl)-alpha-D-glucosaminyl 1-phosphoric acid 2,3-Bis(3-hydroxytetradecanoyl)-b-D-glucosaminyl 1-phosphate 2,3-Bis(3-hydroxytetradecanoyl)-b-D-glucosaminyl 1-phosphoric acid 2,3-Bis(3-hydroxytetradecanoyl)-beta-D-glucosaminyl 1-phosphoric acid 2,3-Bis(3-hydroxytetradecanoyl)-α-D-glucosaminyl 1-phosphate 2,3-Bis(3-hydroxytetradecanoyl)-α-D-glucosaminyl 1-phosphoric acid 2,3-Bis(3-hydroxytetradecanoyl)-β-D-glucosaminyl 1-phosphate 2,3-Bis(3-hydroxytetradecanoyl)-β-D-glucosaminyl 1-phosphoric acid 2,3-Bis(b-hydroxymyristoyl)-a-D-glucosaminyl 1-phosphate 2,3-Bis(b-hydroxymyristoyl)-a-D-glucosaminyl 1-phosphoric acid 2,3-Bis(beta-hydroxymyristoyl)-alpha-D-glucosaminyl 1-phosphate 2,3-Bis(beta-hydroxymyristoyl)-alpha-D-glucosaminyl 1-phosphoric acid 2,3-Bis(β-hydroxymyristoyl)-α-D-glucosaminyl 1-phosphate 2,3-Bis(β-hydroxymyristoyl)-α-D-glucosaminyl 1-phosphoric acid BHMyrGc1P Lipid x Monosaccharide precursor, e coli lipid a C34H66NO12P 711.8611 711.432263093 3-hydroxy-N-[(2R,3R,4R,5S,6R)-5-hydroxy-6-(hydroxymethyl)-4-[(3-hydroxytetradecanoyl)oxy]-2-(phosphonooxy)oxan-3-yl]tetradecanimidic acid 3-hydroxy-N-[(2R,3R,4R,5S,6R)-5-hydroxy-6-(hydroxymethyl)-4-[(3-hydroxytetradecanoyl)oxy]-2-(phosphonooxy)oxan-3-yl]tetradecanimidic acid [H]C(O)(CCCCCCCCCCC)CC(=O)O[C@@]1([H])[C@]([H])(O)[C@@]([H])(CO)O[C@]([H])(OP(O)(O)=O)[C@]1([H])N=C(O)CC([H])(O)CCCCCCCCCCC InChI=1S/C34H66NO12P/c1-3-5-7-9-11-13-15-17-19-21-26(37)23-29(39)35-31-33(32(41)28(25-36)45-34(31)47-48(42,43)44)46-30(40)24-27(38)22-20-18-16-14-12-10-8-6-4-2/h26-28,31-34,36-38,41H,3-25H2,1-2H3,(H,35,39)(H2,42,43,44)/t26?,27?,28-,31-,32-,33-,34-/m1/s1 HEHQDWUWJVPREQ-JIMHHRIFSA-N Cytosol Membrane logp 4.52 ALOGPS logs -4.91 ALOGPS solubility 8.80e-03 g/l ALOGPS logp 5.83 ChemAxon pka_strongest_acidic 0.83 ChemAxon pka_strongest_basic 1.6 ChemAxon iupac 3-hydroxy-N-[(2R,3R,4R,5S,6R)-5-hydroxy-6-(hydroxymethyl)-4-[(3-hydroxytetradecanoyl)oxy]-2-(phosphonooxy)oxan-3-yl]tetradecanimidic acid ChemAxon average_mass 711.8611 ChemAxon mono_mass 711.432263093 ChemAxon smiles [H]C(O)(CCCCCCCCCCC)CC(=O)O[C@@]1([H])[C@]([H])(O)[C@@]([H])(CO)O[C@]([H])(OP(O)(O)=O)[C@]1([H])N=C(O)CC([H])(O)CCCCCCCCCCC ChemAxon formula C34H66NO12P ChemAxon inchi InChI=1S/C34H66NO12P/c1-3-5-7-9-11-13-15-17-19-21-26(37)23-29(39)35-31-33(32(41)28(25-36)45-34(31)47-48(42,43)44)46-30(40)24-27(38)22-20-18-16-14-12-10-8-6-4-2/h26-28,31-34,36-38,41H,3-25H2,1-2H3,(H,35,39)(H2,42,43,44)/t26?,27?,28-,31-,32-,33-,34-/m1/s1 ChemAxon inchikey HEHQDWUWJVPREQ-JIMHHRIFSA-N ChemAxon polar_surface_area 215.8 ChemAxon refractivity 181.08 ChemAxon polarizability 79.77 ChemAxon rotatable_bond_count 30 ChemAxon acceptor_count 11 ChemAxon donor_count 7 ChemAxon physiological_charge -3 ChemAxon formal_charge 0 ChemAxon 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 superpathway of (KDO)<SUB>2</SUB>-lipid A biosynthesis NAGLIPASYN-PWY Specdb::CMs 1083740 Specdb::NmrOneD 252368 Specdb::NmrOneD 252369 Specdb::NmrOneD 252370 Specdb::NmrOneD 252371 Specdb::NmrOneD 252372 Specdb::NmrOneD 252373 Specdb::NmrOneD 252374 Specdb::NmrOneD 252375 Specdb::NmrOneD 252376 Specdb::NmrOneD 252377 Specdb::NmrOneD 252378 Specdb::NmrOneD 252379 Specdb::NmrOneD 252380 Specdb::NmrOneD 252381 Specdb::NmrOneD 252382 Specdb::NmrOneD 252383 Specdb::NmrOneD 252384 Specdb::NmrOneD 252385 Specdb::NmrOneD 252386 Specdb::NmrOneD 252387 Specdb::MsMs 27455 Specdb::MsMs 27456 Specdb::MsMs 27457 Specdb::MsMs 34013 Specdb::MsMs 34014 Specdb::MsMs 34015 10078514 8254052 C04824 16942 BISOHMYR-GLUCOSAMINYL-1P 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 Raetz, C. R. (1984). "The enzymatic synthesis of lipid A: molecular structure and biologic function of monosaccharide precursors." Rev Infect Dis 6:463-471. 6382553 Golenbock, D. T., Will, J. A., Raetz, C. R., Proctor, R. A. (1987). "Lipid X ameliorates pulmonary hypertension and protects sheep from death due to endotoxin." Infect Immun 55:2471-2476. 3308707 Amano, F., Nishijima, M., Akamatsu, Y. (1986). "A monosaccharide precursor of Escherichia coli lipid A has the ability to induce tumor-cytotoxic factor production by a murine macrophage-like cell line, J774.1." J Immunol 136:4122-4127. 3701065 Amano, F., Nishijima, M., Akagawa, K., Akamatsu, Y. (1985). "Enhancement of O2- generation and tumoricidal activity of murine macrophages by a monosaccharide precursor of Escherichia coli lipid A." FEBS Lett 192:263-266. 2998869 CDP-diacylglycerol pyrophosphatase P06282 CDH_ECOLI cdh http://ecmdb.ca/proteins/P06282.xml Lipid-A-disaccharide synthase P10441 LPXB_ECOLI lpxB http://ecmdb.ca/proteins/P10441.xml UDP-2,3-diacylglucosamine hydrolase P43341 LPXH_ECOLI lpxH http://ecmdb.ca/proteins/P43341.xml 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 Water + UDP-2,3-Bis(3-hydroxytetradecanoyl)glucosamine <>2 Hydrogen ion + 2,3-Bis(3-hydroxytetradecanoyl)-beta-D-glucosaminyl 1-phosphate + Uridine 5'-monophosphate R04549 LIPIDXSYNTHESIS-RXN UDP-2,3-Bis(3-hydroxytetradecanoyl)glucosamine + Water <> Uridine 5'-monophosphate + 2,3-Bis(3-hydroxytetradecanoyl)-beta-D-glucosaminyl 1-phosphate R04549 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 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 Water + UDP-2,3-Bis(3-hydroxytetradecanoyl)glucosamine > Hydrogen ion + 2,3-Bis(3-hydroxytetradecanoyl)-beta-D-glucosaminyl 1-phosphate + Uridine 5'-monophosphate LIPIDXSYNTHESIS-RXN 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 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