2.02012-05-31 13:46:17 -06002015-06-03 15:53:47 -0600ECMDB01142M2MDB000273FMNHFMNH is a member of the chemical class known as Flavins. These are compounds containing a flavin (7,8-dimethyl-benzo[g]pteridine-2,4-dione) moiety, whose structure is characterized by an isoalloaxzine tricyclic ring. During their use in different catalytic cycles, the reversible interconversion of oxidized (FMN), semiquinone (FMNHFMNH2Reduced flavin mononucleotideReduced FMNC17H23N4O9P458.3597458.120264866[(5-{7,8-dimethyl-2,4-dioxo-1H,2H,3H,4H,5H,10H-benzo[g]pteridin-10-yl}-2,3,4-trihydroxypentyl)oxy]phosphonic acid(5-{7,8-dimethyl-2,4-dioxo-1H,3H,5H-benzo[g]pteridin-10-yl}-2,3,4-trihydroxypentyl)oxyphosphonic acidCC1=CC2=C(C=C1C)N(CC(O)C(O)C(O)COP(O)(O)=O)C1=C(N2)C(=O)NC(=O)N1InChI=1S/C17H23N4O9P/c1-7-3-9-10(4-8(7)2)21(15-13(18-9)16(25)20-17(26)19-15)5-11(22)14(24)12(23)6-30-31(27,28)29/h3-4,11-12,14,18,22-24H,5-6H2,1-2H3,(H2,27,28,29)(H2,19,20,25,26)YTNIXZGTHTVJBW-UHFFFAOYSA-NCytosollogp-0.17logs-2.85solubility6.42e-01 g/llogp-1.1pka_strongest_acidic1.5pka_strongest_basic-0.52iupac[(5-{7,8-dimethyl-2,4-dioxo-1H,2H,3H,4H,5H,10H-benzo[g]pteridin-10-yl}-2,3,4-trihydroxypentyl)oxy]phosphonic acidaverage_mass458.3597mono_mass458.120264866smilesCC1=CC2=C(C=C1C)N(CC(O)C(O)C(O)COP(O)(O)=O)C1=C(N2)C(=O)NC(=O)N1formulaC17H23N4O9PinchiInChI=1S/C17H23N4O9P/c1-7-3-9-10(4-8(7)2)21(15-13(18-9)16(25)20-17(26)19-15)5-11(22)14(24)12(23)6-30-31(27,28)29/h3-4,11-12,14,18,22-24H,5-6H2,1-2H3,(H2,27,28,29)(H2,19,20,25,26)inchikeyYTNIXZGTHTVJBW-UHFFFAOYSA-Npolar_surface_area200.92refractivity118.51polarizability43.23rotatable_bond_count7acceptor_count10donor_count8physiological_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.PW000942ec00240MetabolicSulfur metabolismThe sulfur metabolism pathway starts in three possible ways. The first is the uptake of sulfate through an active transport reaction via a sulfate transport system containing an ATP-binding protein which hydrolyses ATP. Sulfate is converted by the sulfate adenylyltransferase enzymatic complex to adenosine phosphosulfate through the addition of adenine from a molecule of ATP, along with one phosphate group. Adenosine phosphosulfate is further converted to phoaphoadenosine phosphosulfate through an ATP hydrolysis and dehydrogenation reaction by the adenylyl-sulfate kinase. Phoaphoadenosine phosphosulfate is finally dehydrogenated and converted to sulfite by phosphoadenosine phosphosulfate reductase. This reaction requires magnesium, and adenosine 3',5'-diphosphate is the bi-product. A thioredoxin is also oxidized. Sulfite can also be produced from the dehydrogenation of cyanide along with the conversion of thiosulfate to thiocyanate by the thiosulfate sulfurtransferase enzymatic complex. Sulfite next undergoes a series of reactions that lead to the production of pyruvic acid, which is a precursor for pathways such as gluconeogenesis. The first reaction in this series is the conversion of sulfite to hydrogen sulfide through hygrogenation and the deoxygenation of sulfite to form a water molecule. The reaction is catalyzed by the sulfite reductase [NADPH] flavoprotein alpha and beta components. Siroheme, 4Fe-4S, flavin mononucleotide, and FAD function as cofactors or prosthetic groups. Hydrogen sulfide next undergoes dehydrogenation in a reversible reaction to form L-Cysteine and acetic acid, via the cysteine synthase complex and the coenzyme pyridoxal 5'-phosphate. L-Cysteine is dehydrogenated and converted to 2-aminoacrylic acid (a bronsted acid) and hydrogen sulfide(which may be reused) by a larger enzymatic complex composed of cysteine synthase A/B, protein malY, cystathionine-β-lyase, and tryptophanase, along with the coenzyme pyridoxal 5'-phosphate. 2-aminoacrylic acid isomerizes to 2-iminopropanoate, which along with a water molecule and a hydrogen ion is lastly converted to pyruvic acid and ammonium in a spontaneous fashion.
The second possible initial starting point for sulfur metabolism is the import of taurine(an alternate sulfur source) into the cytoplasm via the taurine ABC transporter complex. Taurine, oxoglutaric acid, and oxygen are converted to sulfite by the alpha-ketoglutarate-dependent taurine dioxygenase. Carbon dioxide, succinic acid, and aminoacetaldehyde are bi-products of this reaction. Sulfite next enters pyruvic acid synthesis as already described.
The third variant of sulfur metabolism starts with the import of an alkyl sulfate into the cytoplasm via an aliphatic sulfonate ABC transporter complex which hydrolyses ATP. The alkyl sulfate is dehydrogenated and along with oxygen is converted to sulfite and an aldehyde by the FMNH2-dependent alkanesulfonate monooxygenase enzyme. Water and flavin mononucleotide(which is used in a subsequent reaction as a prosthetic group) are also produced. Sulfite is next converted to pyruvic acid by the process already described.PW000922ec00920MetabolicPorphyrin and chlorophyll metabolismec00860Butirosin and neomycin biosynthesisec00524Riboflavin metabolismec00740Metabolic pathwayseco01100uracil degradation IIIPWY0-1471two-component alkanesulfonate monooxygenaseALKANEMONOX-PWYSpecdb::CMs1083649Specdb::NmrOneD263688Specdb::NmrOneD263689Specdb::NmrOneD263690Specdb::NmrOneD263691Specdb::NmrOneD263692Specdb::NmrOneD263693Specdb::NmrOneD263694Specdb::NmrOneD263695Specdb::NmrOneD263696Specdb::NmrOneD263697Specdb::NmrOneD263698Specdb::NmrOneD263699Specdb::NmrOneD263700Specdb::NmrOneD263701Specdb::NmrOneD263702Specdb::NmrOneD263703Specdb::NmrOneD263704Specdb::NmrOneD263705Specdb::NmrOneD263706Specdb::NmrOneD263707Specdb::MsMs29525Specdb::MsMs29526Specdb::MsMs29527Specdb::MsMs36083Specdb::MsMs36084Specdb::MsMs36085HMDB01142691C01847FMNH2FMNHKeseler, 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 370:17-25.17765195NAD(P)H-flavin reductaseP0AEN1FRE_ECOLIfrehttp://ecmdb.ca/proteins/P0AEN1.xmlSulfite reductase [NADPH] hemoprotein beta-componentP17846CYSI_ECOLIcysIhttp://ecmdb.ca/proteins/P17846.xmlSulfite reductase [NADPH] flavoprotein alpha-componentP38038CYSJ_ECOLIcysJhttp://ecmdb.ca/proteins/P38038.xmlFerric iron reductase protein fhuFP39405FHUF_ECOLIfhuFhttp://ecmdb.ca/proteins/P39405.xmlFMN reductaseP80644SSUE_ECOLIssuEhttp://ecmdb.ca/proteins/P80644.xmlAlkanesulfonate monooxygenaseP80645SSUD_ECOLIssuDhttp://ecmdb.ca/proteins/P80645.xmlPutative flavin reductase rutFP75893RUTF_ECOLIrutFhttp://ecmdb.ca/proteins/P75893.xmlPutative monooxygenase rutAP75898RUTA_ECOLIrutAhttp://ecmdb.ca/proteins/P75898.xmlFlavin Mononucleotide + Hydrogen ion + NADH > FMNH + NADR05705Flavin Mononucleotide + Hydrogen ion + NADPH <> FMNH + NADPR05706RXN-12444FMNH + Oxygen + Sulfoacetate > Flavin Mononucleotide + Glyoxylic acid + Hydrogen ion + Water + SulfiteFMNH + Isethionic acid + Oxygen > Flavin Mononucleotide + Glycolaldehyde + Hydrogen ion + Water + SulfiteRXN-13418FMNH + Methanesulfonate + Oxygen > Formaldehyde + Flavin Mononucleotide + Hydrogen ion + Water + SulfiteButanesulfonate + FMNH + Oxygen > Butanal + Flavin Mononucleotide + Hydrogen ion + Water + SulfiteRXN0-6973Ethanesulfonate + FMNH + Oxygen > Acetaldehyde + Flavin Mononucleotide + Hydrogen ion + Water + Sulfite2 Ferroxamine + FMNH >2 Iron +2 ferroxamine minus Fe(3) + Flavin Mononucleotide +2 Hydrogen ionFMNH + NAD <> Flavin Mononucleotide + NADH + Hydrogen ionR05705FMNH + NADP <> Flavin Mononucleotide + NADPH + Hydrogen ionR05706Uracil + FMNH + Oxygen <> Ureidoacrylate peracid + Flavin MononucleotideR09936RXN0-6444NAD(P)<sup>+</sup> + FMNH <> NAD(P)H + Flavin Mononucleotide + Hydrogen ionFMNREDUCT-RXNFMNH + NADP < Flavin Mononucleotide + NADPH + Hydrogen ionRXN-12444Thymine + Oxygen + FMNH > (<i>Z</i>)-2-methylureidoacrylate peracid + Flavin Mononucleotide + Hydrogen ionRXN-12886an alkanesulfonate + Oxygen + FMNH > an aldehyde + Sulfite + Water + Flavin Mononucleotide + Hydrogen ionRXN0-280Uracil + Oxygen + FMNH > Hydrogen ion + Ureidoacrylate peracid + Flavin MononucleotideRXN0-6444Butanesulfonate + Oxygen + FMNH > Butanal + Sulfite + Water + Flavin Mononucleotide + Hydrogen ionRXN0-6973Alkanesulfonate + FMNH + Oxygen <> Aldehyde + Flavin Mononucleotide + Sulfite + WaterR07210 Uracil + FMNH + Oxygen + Thymine <> Ureidoacrylate peracid + Flavin Mononucleotide + (Z)-2-Methyl-ureidoacrylate peracidR09936 Alkanesulfonate + FMNH + Oxygen <> Aldehyde + Flavin Mononucleotide + Sulfite + WaterFlavin Mononucleotide + Hydrogen ion + NADH > FMNH + NADFlavin Mononucleotide + Hydrogen ion + NADH > FMNH + NAD