2.02012-05-31 10:26:49 -06002015-09-13 12:56:08 -0600ECMDB00462M2MDB000139AllantoinAllantoin is a member of the chemical class known as Ureides. These are compounds containing an ureide group with the general structure R-CO-NH-CO-N(R)R'', formally derived by the acylation of urea. It is also called 5-ureidohydantoin or glyoxyldiureide. It is a diureide of glyoxylic acid. Allantoin is a compound involved in purine metabolism. It has two forms, (S)(+)-Allantoin and (R)(-)-Allantoin, though only the S form is found in E.coli. Enteric bacteria such as E. coli are able to utilize allantoin as a sole source of nitrogen under anaerobic conditions, but cannot utilize it as a sole source of carbon The first step in allantoin degradation is the opening of the aromatic ring, yielding allantoate, performed by allantoinase. In the next step allantoate is hydrolyzed to S-ureidoglycine by allantoate amidohydrolase. Ureidoglycine spontaneously converts to Ureidoglycolate. Ureidoglycolate dehydrogenase then oxidizes ureidoglycolate to oxalurate. It is believed oxalurate is converted into oxamate and carbamoyl-phosphate, which can be further metabolized to CO2, ammonia and ATP. (PMID 10601204).(S)-allantoin2,5-Dioxo-4-imidazolidinyl-urea4-Ureido-2,5-Imidazolidinedione5-Ureido-Hydantoin5-Ureidohydantoin5-UreidohydrantoinAlantanAllantoinAllantoin (JAN/USP)AllantolAlloxantinAVC/DienestrolcreamCordianineD00121Fancol TOINGlyoxyldiureidGlyoxyldiureideGlyoxylic diureideN-(2,5-Dioxo-4-imidazolidinyl)ureaPsoralonSebicalSeptalanC4H6N4O3158.1154158.043990078(2,5-dioxoimidazolidin-4-yl)ureaallantoin97-59-6NC(=O)NC1NC(=O)NC1=OInChI=1S/C4H6N4O3/c5-3(10)6-1-2(9)8-4(11)7-1/h1H,(H3,5,6,10)(H2,7,8,9,11)POJWUDADGALRAB-UHFFFAOYSA-NSolidCytosolExtra-organismPeriplasmlogp-1.95logs-1.52solubility4.73e+00 g/lmelting_point239 oClogp-2.4pka_strongest_acidic7.95pka_strongest_basic-3.4iupac(2,5-dioxoimidazolidin-4-yl)ureaaverage_mass158.1154mono_mass158.043990078smilesNC(=O)NC1NC(=O)NC1=OformulaC4H6N4O3inchiInChI=1S/C4H6N4O3/c5-3(10)6-1-2(9)8-4(11)7-1/h1H,(H3,5,6,10)(H2,7,8,9,11)inchikeyPOJWUDADGALRAB-UHFFFAOYSA-Npolar_surface_area113.32refractivity32.02polarizability12.89rotatable_bond_count1acceptor_count3donor_count4physiological_charge0formal_charge0glycolate and glyoxylate degradationGlycolic acid is introduced into the cytoplasm through either a glycolate / lactate:H+ symporter or a acetate / glycolate transporter. Once inside, glycolic acid reacts with an oxidized electron-transfer flavoprotein through a glycolate oxidase resulting in a reduced acceptor and glyoxylic acid. Glyoxylic acid can also be obtained from the introduction of glyoxylic acid. It can also be obtained from the metabolism of (S)-allantoin.
S-allantoin is introduced into the cytoplasm through a purine and pyrimidine transporter(allantoin specific). Once inside, the compound reacts with water through a allantoinase resulting in hydrogen ion and allantoic acid. Allantoic acid then reacts with water and hydrogen ion through a allantoate amidohydrolase resulting in a carbon dioxide, ammonium and S-ureidoglycine. The latter compound reacts with water through a S-ureidoglycine aminohydrolase resulting in ammonium and S-ureidoglycolic acid which in turn reacts with a Ureidoglycolate lyase resulting in urea and glyoxylic acid.
Glyoxylic acid can either be metabolized into L-malic acid by a reaction with acetyl-CoA and Water through a malate synthase G which also releases hydrogen ion and Coenzyme A. L-malic acid is then incorporated into the TCA cycle.
Glyoxylic acid can also be metabolized by glyoxylate carboligase, releasing a carbon dioxide and tartronate semialdehyde. The latter compound is then reduced by an NADH driven tartronate semialdehyde reductase 2 resulting in glyceric acid. Glyceric acid is phosphorylated by a glycerate kinase 2 resulting in a 3-phosphoglyceric acid. This compound is then integrated into various other pathways: cysteine biosynthesis, serine biosynthesis and glycolysis and pyruvate dehydrogenase.
PW000827Metabolicinner membrane transportlist of inner membrane transport complexes, transporting compounds from the periplasmic space to the cytosol
This pathway should be updated regularly with the new inner membrae transports addedPW000786Metabolicallantoin degradation (anaerobic)Allantoin can be degraded in anaerobic conditions. The first step involves allantoin being degraded by an allantoinase resulting in an allantoate. This compound in turn is metabolized by reacting with water and 2 hydrogen ions through an allantoate amidohydrolase resulting in the release of a carbon dioxide, ammonium and an S-ureidoglycine. The latter compund is further degrades through a S-ureidoglycine aminohydrolase resulting in the release of an ammonium and an S-ureidoglycolate.
S-ureidoglycolate can be metabolized into oxalurate by two different reactions. The first reactions involves a NAD driven ureidoglycolate dehydrogenase resulting in the release of a hydrogen ion , an NADH and a oxalurate. On the other hand S-ureidoglycolate can react with NADP resulting in the release of an NADPH, a hydroge ion and an oxalurate.
It is hypothesized that oxalurate can interact with a phosphate and release a a carbamoyl phosphate and an oxamate.
The carbamoyl phosphate can be further degraded by reacting with an ADP, and a hydrogen ion through a carbamate kinase resulting in the release of an ammonium , ATP and carbon dioxidePW002050MetabolicSpecdb::CMs552Specdb::CMs553Specdb::CMs554Specdb::CMs1583Specdb::CMs1603Specdb::CMs1778Specdb::CMs3309Specdb::CMs27359Specdb::CMs29056Specdb::CMs30476Specdb::CMs30477Specdb::CMs31149Specdb::CMs31150Specdb::CMs31151Specdb::CMs123555Specdb::CMs167488Specdb::EiMs866Specdb::NmrOneD1233Specdb::NmrOneD1380Specdb::NmrOneD4792Specdb::NmrOneD4793Specdb::NmrOneD144050Specdb::NmrOneD144051Specdb::NmrOneD144052Specdb::NmrOneD144053Specdb::NmrOneD144054Specdb::NmrOneD144055Specdb::NmrOneD144056Specdb::NmrOneD144057Specdb::NmrOneD144058Specdb::NmrOneD144059Specdb::NmrOneD144060Specdb::NmrOneD144061Specdb::NmrOneD144062Specdb::NmrOneD144063Specdb::NmrOneD144064Specdb::NmrOneD144065Specdb::NmrOneD144066Specdb::NmrOneD144067Specdb::NmrOneD144068Specdb::NmrOneD144069Specdb::NmrOneD166437Specdb::MsMs671Specdb::MsMs672Specdb::MsMs673Specdb::MsMs4078Specdb::MsMs4079Specdb::MsMs20090Specdb::MsMs20091Specdb::MsMs20092Specdb::MsMs20444Specdb::MsMs20445Specdb::MsMs20446Specdb::MsMs21035Specdb::MsMs21036Specdb::MsMs21037Specdb::MsMs21104Specdb::MsMs21105Specdb::MsMs21106Specdb::MsMs21641Specdb::MsMs21642Specdb::MsMs21643Specdb::MsMs21995Specdb::MsMs21996Specdb::MsMs21997Specdb::MsMs22586Specdb::MsMs22587Specdb::NmrTwoD1324HMDB00462199C0155115676ALLANTOINAllantoinKeseler, 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 80:2939-2948.18331064Ohdoi 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):123-30.12829005Kastenbauer S, Koedel U, Becker BF, Pfister HW: Oxidative stress in bacterial meningitis in humans. Neurology. 2002 Jan 22;58(2):186-91.11805243Lagendijk J, Ubbink JB, Vermaak WJ: The determination of allantoin, a possible indicator of oxidant status, in human plasma. J Chromatogr Sci. 1995 Apr;33(4):186-93.7738135Goldman SC, Holcenberg JS, Finklestein JZ, Hutchinson R, Kreissman S, Johnson FL, Tou C, Harvey E, Morris E, Cairo MS: A randomized comparison between rasburicase and allopurinol in children with lymphoma or leukemia at high risk for tumor lysis. Blood. 2001 May 15;97(10):2998-3003.11342423Kand'ar R, Zakova P, Muzakova V: Monitoring of antioxidant properties of uric acid in humans for a consideration measuring of levels of allantoin in plasma by liquid chromatography. Clin Chim Acta. 2006 Mar;365(1-2):249-56. Epub 2005 Sep 27.16194528Pavitt DV, de Fonseka S, Al-Khalaf N, Cam JM, Reaveley DA: Assay of serum allantoin in humans by gas chromatography-mass spectrometry. Clin Chim Acta. 2002 Apr;318(1-2):63-70.11880113Alfazema LN, Howells S, Perrett D: Determination of allantoin in biofluids using micellar electrokinetic capillary chromatography. J Chromatogr A. 1998 Aug 21;817(1-2):345-52.9764504Becker BF, Kastenbauer S, Kodel U, Kiesl D, Pfister HW: Urate oxidation in CSF and blood of patients with inflammatory disorders of the nervous system. Nucleosides Nucleotides Nucleic Acids. 2004 Oct;23(8-9):1201-4.15571231Grootveld M, Halliwell B: Measurement of allantoin and uric acid in human body fluids. A potential index of free-radical reactions in vivo? Biochem J. 1987 May 1;243(3):803-8.3663100http://hmdb.ca/system/metabolites/msds/000/000/381/original/HMDB00462.pdf?1358893321AllantoinaseP77671ALLB_ECOLIallBhttp://ecmdb.ca/proteins/P77671.xmlPutative allantoin permeaseP75712ALLP_ECOLIybbWhttp://ecmdb.ca/proteins/P75712.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.xmlAllantoin + Water > Allantoic acid + Hydrogen ion