2.02012-05-31 13:45:10 -06002015-06-03 15:53:44 -0600ECMDB01096M2MDB000253CarbamoylphosphateCarbamoyl phosphate is a precursor of both arginine and pyrimidine biosynthesis. It is a labile and potentially toxic intermediate. Carbamoyl phosphate is produced from carbon dioxide, ammonia, and phosphate (from ATP) by the enzyme carbamoyl phosphate synthase. -- WikipediaCarbamate monoanhydride with phosphateCarbamate monoanhydride with phosphorateCarbamate monoanhydride with phosphoric acidCarbamic acid monoanhydride with phosphorateCarbamic acid monoanhydride with phosphoric acidCarbamoyl phosphateCarbamoyl phosphoric acidCarbamoyl-PCarbamoyl-phosphateCarbamoyl-phosphoric acidCarbamoylphosphateCarbamoylphosphoric acidCarbamyl phosphateCarbamyl phosphoric acidCarbamyl-phosphateCarbamyl-phosphoric acidCH4NO5P141.0199140.982708755(carbamoyloxy)phosphonic acidcarbamoyl-phosphate590-55-6NC(=O)OP(O)(O)=OInChI=1S/CH4NO5P/c2-1(3)7-8(4,5)6/h(H2,2,3)(H2,4,5,6)FFQKYPRQEYGKAF-UHFFFAOYSA-NSolidCytosollogp-1.52logs-0.96solubility1.56e+01 g/llogp-1.2pka_strongest_acidic1.1iupac(carbamoyloxy)phosphonic acidaverage_mass141.0199mono_mass140.982708755smilesNC(=O)OP(O)(O)=OformulaCH4NO5PinchiInChI=1S/CH4NO5P/c2-1(3)7-8(4,5)6/h(H2,2,3)(H2,4,5,6)inchikeyFFQKYPRQEYGKAF-UHFFFAOYSA-Npolar_surface_area109.85refractivity22.48polarizability9.12rotatable_bond_count2acceptor_count4donor_count3physiological_charge-2formal_charge0Alanine, aspartate and glutamate metabolismec00250Arginine and proline metabolismec00330Nitrogen metabolism
The biological process of the nitrogen cycle is a complex interplay among many microorganisms catalyzing different reactions, where nitrogen is found in various oxidation states ranging from +5 in nitrate to -3 in ammonia.
The ability of fixing atmospheric nitrogen by the nitrogenase enzyme complex is present in restricted prokaryotes (diazotrophs). The other reduction pathways are assimilatory nitrate reduction and dissimilatory nitrate reduction both for conversion to ammonia, and denitrification. Denitrification is a respiration in which nitrate or nitrite is reduced as a terminal electron acceptor under low oxygen or anoxic conditions, producing gaseous nitrogen compounds (N2, NO and N2O) to the atmosphere.
Nitrate can be introduced into the cytoplasm through a nitrate:nitrite antiporter NarK or a nitrate / nitrite transporter NarU. Nitrate is then reduced by a Nitrate Reductase resulting in the release of water, an acceptor and a Nitrite. Nitrite can also be introduced into the cytoplasm through a nitrate:nitrite antiporter NarK
Nitrite can be reduced a NADPH dependent nitrite reductase resulting in water and NAD and Ammonia.
Nitrite can interact with hydrogen ion, ferrocytochrome c through a cytochrome c-552 ferricytochrome resulting in the release of ferricytochrome c, water and ammonia
Another process by which ammonia is produced is by a reversible reaction of hydroxylamine with a reduced acceptor through a hydroxylamine reductase resulting in an acceptor, water and ammonia.
Water and carbon dioxide react through a carbonate dehydratase resulting in carbamic acid. This compound reacts spontaneously with hydrogen ion resulting in the release of carbon dioxide and ammonia. Carbon dioxide can interact with water through a carbonic anhydrase resulting in hydrogen carbonate. This compound interacts with cyanate and hydrogen ion through a cyanate hydratase resulting in a carbamic acid.
Ammonia can be metabolized by reacting with L-glutamine and ATP driven glutamine synthetase resulting in ADP, phosphate and L-glutamine. The latter compound reacts with oxoglutaric acid and hydrogen ion through a NADPH dependent glutamate synthase resulting in the release of NADP and L-glutamic acid. L-glutamic acid reacts with water through a NADP-specific glutamate dehydrogenase resulting in the release of oxoglutaric acid, NADPH, hydrogen ion and ammonia.
PW000755ec00910MetabolicPurine metabolismec00230Pyrimidine 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.PW000942ec00240MetabolicMicrobial metabolism in diverse environmentsec01120Metabolic pathwayseco01100arginine metabolismThe metabolism of L-arginine starts with the acetylation of L-glutamic acid resulting in a N-acetylglutamic acid while releasing a coenzyme A and a hydrogen ion. N-acetylglutamic acid is then phosphorylated via an ATP driven acetylglutamate kinase which yields a N-acetyl-L-glutamyl 5-phosphate. This compound undergoes a NDPH dependent reduction resulting in N-acetyl-L-glutamate 5-semialdehyde. This compound reacts with L-glutamic acid through a acetylornithine aminotransferase / N-succinyldiaminopimelate aminotransferase to produce a N-acetylornithine which is then deacetylated through a acetylornithine deacetylase which yield an ornithine.
L-glutamine is used to synthesize carbamoyl phosphate through the interaction of L-glutamine, water, ATP, and hydrogen carbonate. This reaction yields ADP, L-glutamic acid, phosphate, and hydrogen ion.
Carbamoyl phosphate and ornithine are used to catalyze the production of citrulline through an ornithine carbamoyltransferase. Citrulline reacts with L-aspartic acid through an ATP dependent enzyme, argininosuccinate synthase to produce pyrophosphate, AMP and argininosuccinic acid. Argininosussinic acid is then lyase to produce L-arginine and fumaric acid.
L-arginine can be metabolized into succinic acid by two different sets of reactions:
1. Arginine reacts with succinyl-CoA through a arginine N-succinyltransferase resulting in N2-succinyl-L-arginine while releasing CoA and Hydrogen Ion. N2-succinyl-L-arginine is then dihydrolase to produce a N2-succinyl-L-ornithine through a N-succinylarginine dihydrolase. This compound in turn reacts with oxoglutaric acid through succinylornithine transaminase resulting in L-glutamic acid and N2-succinyl-L-glutamic acid 5-semialdehyde. This compoud in turn reacts with a NAD dependent dehydrogenase resulting in N2-succinylglutamate while releasing NADH and hydrogen ion. N2-succinylglutamate reacts with water through a succinylglutamate desuccinylase resulting in L-glutamic acid and
a succinic acid. The succinic acid is then incorporated in the TCA cycle
2.Argine reacts with carbon dioxide and a hydrogen ion through a biodegradative arginine decarboxylase, resulting in Agmatine. This compound is then transformed into putrescine by reacting with water and an agmatinase, and releasing urea. Putrescine can be metabolized by reaction with either l-glutamic acid or oxoglutaric acid. If putrescine reacts with L-glutamic acid, it reacts through an ATP mediated gamma-glutamylputrescine producing a hydrogen ion, ADP, phosphate and gamma-glutamyl-L-putrescine. This compound is reduced by interacting with oxygen, water and a gamma-glutamylputrescine oxidoreductase resulting in ammonium, hydrogen peroxide and 4-gamma-glutamylamino butanal. This compound is dehydrogenated through a NADP mediated reaction lead by gamma-glutamyl-gamma-aminobutaryaldehyde dehydrogenase resulting in hydrogen ion, NADPH and 4-glutamylamino butanoate. In turn, the latter compound reacts with water through a gamma-glutamyl-gamma-aminobutyrate hydrolase resulting in L-glutamic acid and Gamma aminobutyric acid. On the other hand, if putrescine reacts with oxoglutaric acid through a putrescine aminotransferase, it results in L-glutamic acid, and a 4-aminobutyraldehyde. This compound reacts with water through a NAD dependent gamma aminobutyraldehyde dehydrogenase resulting in hydrogen ion, NADH and gamma-aminobutyric acid.
Gamma Aaminobutyric acid reacts with oxoglutaric acid through 4-aminobutyrate aminotransferase resulting in L-glutamic acid and succinic acid semialdehyde. This compound in turn can react with with either NADP or NAD to result in the production of succinic acid through succinate-semialdehyde dehydrogenase or aldehyde dehydrogenase-like protein yneI respectively. Succinic acid can then be integrated in the TCA cycle.
L-arginine is eventua lly metabolized into succinic acid which then goes to the TCA cyclePW000790Metabolicallantoin 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 dioxidePW002050Metabolicarginine biosynthesis IARGSYN-PWYallantoin degradation IV (anaerobic)PWY0-41uridine-5'-phosphate biosynthesisPWY-5686Specdb::CMs2852Specdb::CMs133803Specdb::CMs141537Specdb::NmrOneD275278Specdb::NmrOneD275279Specdb::NmrOneD275280Specdb::NmrOneD275281Specdb::NmrOneD275282Specdb::NmrOneD275283Specdb::NmrOneD275284Specdb::NmrOneD275285Specdb::NmrOneD275286Specdb::NmrOneD275287Specdb::NmrOneD275288Specdb::NmrOneD275289Specdb::NmrOneD275290Specdb::NmrOneD275291Specdb::NmrOneD275292Specdb::NmrOneD275293Specdb::NmrOneD275294Specdb::NmrOneD275295Specdb::NmrOneD275296Specdb::NmrOneD275297Specdb::MsMs20381Specdb::MsMs20382Specdb::MsMs20383Specdb::MsMs21932Specdb::MsMs21933Specdb::MsMs21934Specdb::MsMs2718123Specdb::MsMs2718124Specdb::MsMs2718125Specdb::MsMs2963907Specdb::MsMs2963908Specdb::MsMs2963909HMDB01096278272C0016917672CARBAMOYL-PCPCarbamoyl phosphateKeseler, 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 80:2939-2948.18331064Sigoillot FD, Kotsis DH, Serre V, Sigoillot SM, Evans DR, Guy HI: Nuclear localization and mitogen-activated protein kinase phosphorylation of the multifunctional protein CAD. J Biol Chem. 2005 Jul 8;280(27):25611-20. Epub 2005 May 12.15890648Struck J, Uhlein M, Morgenthaler NG, Furst W, Hoflich C, Bahrami S, Bergmann A, Volk HD, Redl H: Release of the mitochondrial enzyme carbamoyl phosphate synthase under septic conditions. Shock. 2005 Jun;23(6):533-8.15897806Schnater JM, Bruder E, Bertschin S, Woodtli T, de Theije C, Pietsch T, Aronson DC, von Schweinitz D, Lamers WH, Kohler ES: Subcutaneous and intrahepatic growth of human hepatoblastoma in immunodeficient mice. J Hepatol. 2006 Sep;45(3):377-86. Epub 2006 May 3.16780998Chen KF, Lai YY, Sun HS, Tsai SJ: Transcriptional repression of human cad gene by hypoxia inducible factor-1alpha. Nucleic Acids Res. 2005 Sep 9;33(16):5190-8. Print 2005.16155188Carbamoyl-phosphate synthase large chainP00968CARB_ECOLIcarBhttp://ecmdb.ca/proteins/P00968.xmlOrnithine carbamoyltransferase chain IP04391OTC1_ECOLIargIhttp://ecmdb.ca/proteins/P04391.xmlOrnithine carbamoyltransferase chain FP06960OTC2_ECOLIargFhttp://ecmdb.ca/proteins/P06960.xmlCarbamoyl-phosphate synthase small chainP0A6F1CARA_ECOLIcarAhttp://ecmdb.ca/proteins/P0A6F1.xmlAspartate carbamoyltransferase catalytic chainP0A786PYRB_ECOLIpyrBhttp://ecmdb.ca/proteins/P0A786.xmlAspartate carbamoyltransferase regulatory chainP0A7F3PYRI_ECOLIpyrIhttp://ecmdb.ca/proteins/P0A7F3.xmlCarbamate kinaseP37306ARCC_ECOLIarcChttp://ecmdb.ca/proteins/P37306.xmlCarbamate kinase-like protein yahIP77624ARCM_ECOLIyahIhttp://ecmdb.ca/proteins/P77624.xmlCarbamate kinase-like protein yqeAQ46807ARCL_ECOLIyqeAhttp://ecmdb.ca/proteins/Q46807.xmlL-Aspartic acid + Carbamoylphosphate <> Ureidosuccinic acid + Hydrogen ion + PhosphateR01397ASPCARBTRANS-RXN2 Adenosine triphosphate + L-Glutamine + Water + Hydrogen carbonate >2 ADP + Carbamoylphosphate + L-Glutamate +2 Hydrogen ion + PhosphateR00575CARBPSYN-RXNAdenosine triphosphate + Carbon dioxide + Ammonium <> ADP + Carbamoylphosphate +2 Hydrogen ionCarbamoylphosphate + Ornithine + L-Ornithine <> Citrulline + Hydrogen ion + PhosphateR01398ORNCARBAMTRANSFER-RXNAdenosine triphosphate + Ammonia + Carbon dioxide <> ADP + CarbamoylphosphateR001502 Adenosine triphosphate + L-Glutamine + Hydrogen carbonate + Water <>2 ADP + Phosphate + L-Glutamate + CarbamoylphosphateR00575Adenosine triphosphate + Carbamic acid <> ADP + CarbamoylphosphateR01395Carbamoylphosphate + L-Aspartic acid <> Phosphate + Ureidosuccinic acidR01397Carbamoylphosphate + Ornithine <> Phosphate + CitrullineR01398L-Aspartic acid + Carbamoylphosphate > Hydrogen ion + Ureidosuccinic acid + PhosphateASPCARBTRANS-RXNAmmonia + Carbon dioxide + Adenosine triphosphate < Hydrogen ion + Carbamoylphosphate + ADPR00150CARBAMATE-KINASE-RXNAdenosine triphosphate + L-Glutamine + Hydrogen carbonate + Water > Hydrogen ion + Carbamoylphosphate + L-Glutamate + Phosphate + ADPCARBPSYN-RXNOrnithine + Carbamoylphosphate <> Hydrogen ion + Citrulline + PhosphateR01398ORNCARBAMTRANSFER-RXNOxamate + Carbamoylphosphate < Phosphate + OxalureateOXAMATE-CARBAMOYLTRANSFERASE-RXNAdenosine triphosphate + Hydrogen carbonate + Ammonia > ADP + Phosphate + Carbamoylphosphate + Hydrogen ionRXN-13202Adenosine triphosphate + Ammonia + Carbon dioxide > ADP + Carbamoylphosphate2 Adenosine triphosphate + L-Glutamine + Carbonic acid + Water >2 ADP + Inorganic phosphate + L-Glutamate + CarbamoylphosphateCarbamoylphosphate + Ornithine > Inorganic phosphate + CitrullineCarbamoylphosphate + L-Aspartic acid > Inorganic phosphate + Ureidosuccinic acid2 Adenosine triphosphate + L-Glutamine + Hydrogen carbonate + Water + Ammonia + Carbamic acid + Carboxyphosphate <>2 ADP + Phosphate + L-Glutamate + CarbamoylphosphateR00575 Ornithine + Carbamoylphosphate + Ornithine > Phosphate + Hydrogen ion + CitrullinePW_R002676Hydrogen carbonate + Water + L-Glutamine + 2 Adenosine triphosphate >2 Adenosine diphosphate + Phosphate + L-Glutamic acid +2 Hydrogen ion + Carbamoylphosphate +2 ADP + L-GlutamatePW_R002677Carbamoylphosphate + L-Aspartic acid + L-Aspartic acid > Phosphate + Hydrogen ion + N-carbamoyl-L-aspartatePW_R003526Carbamoylphosphate + ADP + 2 Hydrogen ion > Ammonium + Adenosine triphosphate + Carbon dioxidePW_R005991L-Aspartic acid + Carbamoylphosphate <> Ureidosuccinic acid + Hydrogen ion + PhosphateCarbamoylphosphate + Ornithine + L-Ornithine <> Citrulline + Hydrogen ion + Phosphate2 Adenosine triphosphate + L-Glutamine + Water + Hydrogen carbonate >2 ADP + Carbamoylphosphate + L-Glutamate +2 Hydrogen ion + PhosphateAdenosine triphosphate + Ammonia + Carbon dioxide <> ADP + CarbamoylphosphateAdenosine triphosphate + Carbamic acid <> ADP + CarbamoylphosphateL-Aspartic acid + Carbamoylphosphate <> Ureidosuccinic acid + Hydrogen ion + Phosphate2 Adenosine triphosphate + L-Glutamine + Water + Hydrogen carbonate >2 ADP + Carbamoylphosphate + L-Glutamate +2 Hydrogen ion + Phosphate