2.02012-05-31 10:22:08 -06002015-06-03 15:53:19 -0600ECMDB00157M2MDB000059HypoxanthineHypoxanthine is a naturally occurring purine derivative and a reaction intermediate in the metabolism of adenosine and in the formation of nucleic acids by the salvage pathway. Hypoxanthine is also a spontaneous deamination product of adenine.1,7-Dihydro-6H-purin-6-one1,7-Dihydro-6H-purine-6-one1H,7H-Hypoxanthine3H-Purin-6-ol4-Hydroxy-1H-purine6(1H)-Purinone6-Hydroxy-1H-purine6-Hydroxypurine6-Oxopurine7H-Purin-6-ol9H-Purin-6(1H)-one9H-Purin-6-olHypoxanthine enolPurin-6(1H)-onePurin-6(3H)-onePurin-6-olPurine-6-olSarcineSarkinSarkineC5H4N4O136.1115136.038510777H-purin-6-ol6-hydroxypurine68-94-0OC1=NC=NC2=C1NC=N2InChI=1S/C5H4N4O/c10-5-3-4(7-1-6-3)8-2-9-5/h1-2H,(H2,6,7,8,9,10)FDGQSTZJBFJUBT-UHFFFAOYSA-NSolidCytosolExtra-organismPeriplasmlogp-0.55logs-1.02solubility1.30e+01 g/lmelting_point150 oClogp-0.048pka_strongest_acidic8.72pka_strongest_basic1.73iupac7H-purin-6-olaverage_mass136.1115mono_mass136.03851077smilesOC1=NC=NC2=C1NC=N2formulaC5H4N4OinchiInChI=1S/C5H4N4O/c10-5-3-4(7-1-6-3)8-2-9-5/h1-2H,(H2,6,7,8,9,10)inchikeyFDGQSTZJBFJUBT-UHFFFAOYSA-Npolar_surface_area74.69refractivity35.5polarizability11.82rotatable_bond_count0acceptor_count4donor_count2physiological_charge0formal_charge0Purine metabolismec00230Drug metabolism - other enzymesec00983Metabolic pathwayseco01100adenine and adenosine salvage IThe salvage of adenine begins with adenine being transporter into the cytosol through a adeP hydrogen symporter. Once in the cytosol adenine is degraded by reacting with a ribose-1-phosphate through an adenosine phosphorylase resulting in the release of a phosphate and adenosine. Adenosine is then deaminated by reacting with water, a hydrogen ion and an adenosine deaminase resulting in the release of an ammonium and a inosine . Inosine then reacts with a phosphate through a inosine phosphorylase resulting in the release of a ribose 1-phosphate and a hypoxanthine. Hypoxanthine reacts with a PRPP through a hypoxanthine phosphoribosyltransferase resulting in the release of a pyrophosphate and a IMP molecule.PW002069Metabolicpurine deoxyribonucleosides degradationPW002077Metabolicpurine ribonucleosides degradationPurine ribonucleoside degradation leads to the production of alpha-D-ribose-1-phosphate.
Xanthosine is transported into the cytosol through a xapB. Once in the cytosol xanthosine interacts with phosphate through a xanthosine phosphorylase resulting in the release of a xanthine and a alpha-D-ribose-1-phosphate.
Adenosine is transported through a nupC or a nupG transporter, once inside the cytosol it can either react with a phosphate through a adenosine phosphorylase resultin in the release of a adenine and an alpha-D-ribose-1-phosphate. Adenosine reacts with water and hydrogen ion through a adenosine deaminase resulting in the release of ammonium and inosine. Inosine reacts with phosphate through a inosine phosphorylase resulting in the release of a hypoxanthine and an alpha-D-ribose-1-phosphate.
Guanosine reacts with a phosphate through a guanosine phosphorylase resulting in the release of a guanine and a alpha-D-ribose-1-phosphate.PW002076Metabolicadenosine nucleotides degradationThe degradation of of adenosine nucleotides starts with AMP reacting with water through a nucleoside monophosphate phosphatase results in the release of phosphate and a adenosine. Adenosine reacts with water and hydrogen ion through an adenosine deaminase resulting in the release of ammonium and a inosine. Inosine reacts with phosphate through a inosine phosphorylase resulting in the release of an alpha-D-ribose-1-phosphate and an hypoxanthine. Hypoxanthine reacts with a water molecule and a NAD molecule through an hypoxanthine hydroxylase resulting in the release of an hydrogen ion, an NADH and a xanthine. Xanthine in turn is degraded by reacting with a water molecule and a NAD through xanthine NAD oxidoreductase resulting in the release of NADH, a hydrogen ion and urate.PW002091Metabolicadenine and adenosine salvage IIIPWY-6609purine ribonucleosides degradation to ribose-1-phosphatePWY0-1296purine deoxyribonucleosides degradationPWY0-1297adenosine nucleotides degradation IISALVADEHYPOX-PWYSpecdb::CMs380Specdb::CMs381Specdb::CMs382Specdb::CMs1487Specdb::CMs2948Specdb::CMs29560Specdb::CMs30193Specdb::CMs30574Specdb::CMs30876Specdb::CMs31029Specdb::CMs31967Specdb::CMs31968Specdb::CMs37327Specdb::CMs169563Specdb::CMs1051726Specdb::CMs1051727Specdb::CMs1051729Specdb::EiMs325Specdb::NmrOneD1116Specdb::NmrOneD2582Specdb::NmrOneD3276Specdb::NmrOneD4910Specdb::NmrOneD4911Specdb::NmrOneD5892Specdb::NmrOneD5893Specdb::NmrOneD5894Specdb::NmrOneD5895Specdb::NmrOneD5896Specdb::NmrOneD5897Specdb::NmrOneD5898Specdb::NmrOneD5899Specdb::NmrOneD5900Specdb::NmrOneD5901Specdb::NmrOneD5902Specdb::NmrOneD5903Specdb::NmrOneD5904Specdb::NmrOneD5905Specdb::NmrOneD5906Specdb::NmrOneD5907Specdb::NmrOneD5908Specdb::NmrOneD5909Specdb::NmrOneD5910Specdb::NmrOneD5911Specdb::MsMs242Specdb::MsMs243Specdb::MsMs244Specdb::MsMs3130Specdb::MsMs3131Specdb::MsMs3132Specdb::MsMs3133Specdb::MsMs3134Specdb::MsMs3135Specdb::MsMs3136Specdb::MsMs3137Specdb::MsMs3138Specdb::MsMs3139Specdb::MsMs3140Specdb::MsMs3141Specdb::MsMs3142Specdb::MsMs3143Specdb::MsMs3144Specdb::MsMs3145Specdb::MsMs3146Specdb::MsMs3147Specdb::MsMs3148Specdb::MsMs3149Specdb::MsMs3150Specdb::MsMs3151Specdb::NmrTwoD973Specdb::NmrTwoD1175HMDB00157790768C0026217368HYPOXANTHINEHPAHypoxanthineKeseler, 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 80:2939-2948.18331064Ishii, 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 316:593-597.17379776Sreekumar 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):910-4.19212411Eells JT, Spector R: Purine and pyrimidine base and nucleoside concentrations in human cerebrospinal fluid and plasma. Neurochem Res. 1983 Nov;8(11):1451-7.6656991Ohdoi 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):123-30.12829005Nakayama Y, Kinoshita A, Tomita M: Dynamic simulation of red blood cell metabolism and its application to the analysis of a pathological condition. Theor Biol Med Model. 2005 May 9;2(1):18.15882454Bullo B, Marlewski M, Smolenski RT, Rutkowski B, Swierczynski J, Manitius J: Erythrocyte nucleotides and blood hypoxanthine in patients with uremia evaluated immediately and 24 hours after hemodialysis. Ren Fail. 1996 Mar;18(2):247-52.8723362Ihara H, Shino Y, Morita Y, Kawaguchi E, Hashizume N, Yoshida M: Is skeletal muscle damaged by the oxidative stress following anaerobic exercise? J Clin Lab Anal. 2001;15(5):239-43.11574951Inokuchi T, Moriwaki Y, Takahashi S, Tsutsumi Z, Ka T, Yamamoto A, Cheng J, Hashimoto-Tamaoki T, Hada T, Yamamoto T: Identification of a new point mutation in hypoxanthine phosphoribosyl transferase responsible for hyperuricemia in a female patient. Metabolism. 2004 Nov;53(11):1500-2.15536609Niklasson F: Simultaneous liquid-chromatographic determination of hypoxanthine, xanthine, urate, and creatinine in cerebrospinal fluid, with direct injection. Clin Chem. 1983 Aug;29(8):1543-6.6872216Pietz J, Guttenberg N, Gluck L: Hypoxanthine: a marker for asphyxia. Obstet Gynecol. 1988 Nov;72(5):762-6.3140152Saari H: Oxygen derived free radicals and synovial fluid hyaluronate. Ann Rheum Dis. 1991 Jun;50(6):389-92.1711835Castro-Gago M, Rodriguez IN, Rodriguez-Nunez A, Guitian JP, Rocamonde SL, Rodriguez-Segade S: Therapeutic criteria in hydrocephalic children. Childs Nerv Syst. 1989 Dec;5(6):361-3.2611770Storm H, Rognum TO, Saugstad OD, Skullerud K, Reichelt KL: Beta-endorphin immunoreactivity in spinal fluid and hypoxanthine in vitreous humour related to brain stem gliosis in sudden infant death victims. Eur J Pediatr. 1994 Sep;153(9):675-81.7957429Koellner G, Luic M, Shugar D, Saenger W, Bzowska A: Crystal structure of calf spleen purine nucleoside phosphorylase in a complex with hypoxanthine at 2.15 A resolution. J Mol Biol. 1997 Jan 17;265(2):202-16.9020983Kaya M, Moriwaki Y, Ka T, Inokuchi T, Yamamoto A, Takahashi S, Tsutsumi Z, Tsuzita J, Oku Y, Yamamoto T: Plasma concentrations and urinary excretion of purine bases (uric acid, hypoxanthine, and xanthine) and oxypurinol after rigorous exercise. Metabolism. 2006 Jan;55(1):103-7.16324927Smolenska Z, Kaznowska Z, Zarowny D, Simmonds HA, Smolenski RT: Effect of methotrexate on blood purine and pyrimidine levels in patients with rheumatoid arthritis. Rheumatology (Oxford). 1999 Oct;38(10):997-1002.10534552Saiki S, Sato T, Kohzuki M, Kamimoto M, Yosida T: Changes in serum hypoxanthine levels by exercise in obese subjects. Metabolism. 2001 Jun;50(6):627-30.11398135Gudbjornsson B, Zak A, Niklasson F, Hallgren R: Hypoxanthine, xanthine, and urate in synovial fluid from patients with inflammatory arthritides. Ann Rheum Dis. 1991 Oct;50(10):669-72.1958086Saiki S, Sato T, Hiwatari M, Harada T, Oouchi M, Kamimoto M: Relation between changes in serum hypoxanthine levels by exercise and daily physical activity in the elderly. Tohoku J Exp Med. 1999 May;188(1):71-4.10494902 Shaw, Elliott.New synthesis of the purines adenine, hypoxanthine, xanthine, and isoguanine. Journal of Biological Chemistry (1950), 185 439-47.Hypoxanthine phosphoribosyltransferaseP0A9M2HPRT_ECOLIhpthttp://ecmdb.ca/proteins/P0A9M2.xmlXanthine phosphoribosyltransferaseP0A9M5XGPT_ECOLIgpthttp://ecmdb.ca/proteins/P0A9M5.xmlPurine nucleoside phosphorylase deoD-typeP0ABP8DEOD_ECOLIdeoDhttp://ecmdb.ca/proteins/P0ABP8.xmlNon-specific ribonucleoside hydrolase rihCP22564RIHC_ECOLIrihChttp://ecmdb.ca/proteins/P22564.xmlAdenine deaminaseP31441ADEC_ECOLIadehttp://ecmdb.ca/proteins/P31441.xmlPyrimidine-specific ribonucleoside hydrolase rihBP33022RIHB_ECOLIrihBhttp://ecmdb.ca/proteins/P33022.xmlPutative xanthine dehydrogenase yagS FAD-binding subunitP77324YAGS_ECOLIyagShttp://ecmdb.ca/proteins/P77324.xmlPutative xanthine dehydrogenase yagR molybdenum-binding subunitP77489YAGR_ECOLIyagRhttp://ecmdb.ca/proteins/P77489.xmlXanthine dehydrogenase molybdenum-binding subunitQ46799XDHA_ECOLIxdhAhttp://ecmdb.ca/proteins/Q46799.xmlXanthine dehydrogenase FAD-binding subunitQ46800XDHB_ECOLIxdhBhttp://ecmdb.ca/proteins/Q46800.xmlXanthine dehydrogenase iron-sulfur-binding subunitQ46801XDHC_ECOLIxdhChttp://ecmdb.ca/proteins/Q46801.xmlXanthosine phosphorylaseP45563XAPA_ECOLIxapAhttp://ecmdb.ca/proteins/P45563.xmlPaoABC aldehyde oxidoreductase, 2Fe-2S subunitP77165paoAhttp://ecmdb.ca/proteins/P77165.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.xmlHypoxanthine + Phosphoribosyl pyrophosphate <> Inosinic acid + PyrophosphateR01132HYPOXANPRIBOSYLTRAN-RXNDeoxyinosine + Phosphate <> Deoxyribose 1-phosphate + HypoxanthineR02748Inosine + Phosphate <> Hypoxanthine + Ribose-1-phosphateINOPHOSPHOR-RXNWater + Hypoxanthine + NAD > Hydrogen ion + NADH + XanthineR01768RXN-7682Water + Inosine > Hypoxanthine + RiboseR01770Adenine + Hydrogen ion + Water > Hypoxanthine + AmmoniumInosinic acid + Pyrophosphate <> Hypoxanthine + Phosphoribosyl pyrophosphateR01132Adenine + Water <> Hypoxanthine + AmmoniaR01244Hypoxanthine + NAD + Water <> Xanthine + NADH + Hydrogen ionR01768Inosine + Water <> Hypoxanthine + RiboseR01770Inosine + Phosphate <> Hypoxanthine + alpha-D-Ribose 1-phosphateR01863Water + Adenine > Ammonia + HypoxanthineR01244ADENINE-DEAMINASE-RXNDeoxyinosine + Phosphate <> deoxyribose-1-phosphate + HypoxanthineDEOXYINOPHOSPHOR-RXNPyrophosphate + Inosinic acid < Phosphoribosyl pyrophosphate + HypoxanthineHYPOXANPRIBOSYLTRAN-RXNInosine + Water > D-ribose + HypoxanthineINOSINE-NUCLEOSIDASE-RXNInosinic acid + Pyrophosphate > Hypoxanthine + Phosphoribosyl pyrophosphateHypoxanthine + NAD + Water > Xanthine + NADHInosine + Phosphate > Ribose-1-phosphate + HypoxanthinePW_R006050Hypoxanthine + Phosphoribosyl pyrophosphate > Inosinic acid + PyrophosphatePW_R006052Water + Hypoxanthine + NAD > Hydrogen ion + NADH + XanthineWater + Hypoxanthine + NAD > Hydrogen ion + NADH + XanthineWater + Hypoxanthine + NAD > Hydrogen ion + NADH + Xanthine48 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/h277.0uM0.037 oCBW25113Stationary Phase, glucose limited11080000Ishii, 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