2.0 2015-06-04 15:12:54 -0600 2015-08-05 16:22:04 -0600 ECMDB23749 M2MDB004174 Thioredoxin Proteins that act as antioxidants by facilitating the reduction of other proteins by cysteine thiol-disulfide exchange 2 Thiol L histidine betaine 2-Thiol-L-histidine-betaine Thioneine C9H16N3O2S 230.31 230.095774361 [(1S)-1-carboxy-2-(2-sulfanyl-1H-imidazol-4-yl)ethyl]trimethylazanium [(1S)-1-carboxy-2-(2-sulfanyl-1H-imidazol-4-yl)ethyl]trimethylazanium 52500-60-4 C[N+](C)(C)[C@@H](CC1=CNC(S)=N1)C(O)=O InChI=1S/C9H15N3O2S/c1-12(2,3)7(8(13)14)4-6-5-10-9(15)11-6/h5,7H,4H2,1-3H3,(H2-,10,11,13,14,15)/p+1/t7-/m0/s1 SSISHJJTAXXQAX-ZETCQYMHSA-O logp -0.09 ALOGPS logs -3.83 ALOGPS solubility 3.92e-02 g/l ALOGPS logp -4.3 ChemAxon pka_strongest_acidic 1.87 ChemAxon pka_strongest_basic 5.07 ChemAxon iupac [(1S)-1-carboxy-2-(2-sulfanyl-1H-imidazol-4-yl)ethyl]trimethylazanium ChemAxon average_mass 230.31 ChemAxon mono_mass 230.095774361 ChemAxon smiles C[N+](C)(C)[C@@H](CC1=CNC(S)=N1)C(O)=O ChemAxon formula C9H16N3O2S ChemAxon inchi InChI=1S/C9H15N3O2S/c1-12(2,3)7(8(13)14)4-6-5-10-9(15)11-6/h5,7H,4H2,1-3H3,(H2-,10,11,13,14,15)/p+1/t7-/m0/s1 ChemAxon inchikey SSISHJJTAXXQAX-ZETCQYMHSA-O ChemAxon polar_surface_area 65.98 ChemAxon refractivity 70.96 ChemAxon polarizability 23.88 ChemAxon rotatable_bond_count 4 ChemAxon acceptor_count 3 ChemAxon donor_count 3 ChemAxon physiological_charge 1 ChemAxon formal_charge 1 ChemAxon Glutathione metabolism The biosynthesis of glutathione starts with the introduction of L-glutamic acid through either a glutamate:sodium symporter, glutamate / aspartate : H+ symporter GltP or a glutamate / aspartate ABC transporter. Once in the cytoplasm, L-glutamice acid reacts with L-cysteine through an ATP glutamate-cysteine ligase resulting in gamma-glutamylcysteine. This compound reacts which Glycine through an ATP driven glutathione synthetase thus catabolizing Glutathione. This compound is metabolized through a spontaneous reaction with an oxidized glutaredoxin resulting in a reduced glutaredoxin and an oxidized glutathione. This compound is reduced by a NADPH glutathione reductase resulting in a glutathione. PW000833 ec00480 Metabolic Purine metabolism ec00230 Pyrimidine metabolism The 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. PW000942 ec00240 Metabolic Selenoamino acid metabolism ec00450 Sulfur metabolism The 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. PW000922 ec00920 Metabolic Microbial metabolism in diverse environments ec01120 Metabolic pathways eco01100 Specdb::NmrOneD 286835 Specdb::NmrOneD 286836 Specdb::NmrOneD 286837 Specdb::NmrOneD 286838 Specdb::NmrOneD 286839 Specdb::NmrOneD 286840 Specdb::NmrOneD 286841 Specdb::NmrOneD 286842 Specdb::NmrOneD 286843 Specdb::NmrOneD 286844 Specdb::NmrOneD 286845 Specdb::NmrOneD 286846 Specdb::NmrOneD 286847 Specdb::NmrOneD 286848 Specdb::NmrOneD 286849 Specdb::NmrOneD 286850 Specdb::NmrOneD 286851 Specdb::NmrOneD 286852 Specdb::NmrOneD 286853 Specdb::NmrOneD 286854 Specdb::MsMs 1242046 Specdb::MsMs 1242047 Specdb::MsMs 1242048 C00342 Ribonucleoside-diphosphate reductase 1 subunit alpha P00452 RIR1_ECOLI nrdA http://ecmdb.ca/proteins/P00452.xml Thioredoxin reductase P0A9P4 TRXB_ECOLI trxB http://ecmdb.ca/proteins/P0A9P4.xml Cysteine synthase A P0ABK5 CYSK_ECOLI cysK http://ecmdb.ca/proteins/P0ABK5.xml Cysteine synthase B P16703 CYSM_ECOLI cysM http://ecmdb.ca/proteins/P16703.xml Phosphoadenosine phosphosulfate reductase P17854 CYSH_ECOLI cysH http://ecmdb.ca/proteins/P17854.xml Anaerobic ribonucleoside-triphosphate reductase P28903 NRDD_ECOLI nrdD http://ecmdb.ca/proteins/P28903.xml Ribonucleoside-diphosphate reductase 2 subunit beta P37146 RIR4_ECOLI nrdF http://ecmdb.ca/proteins/P37146.xml Ribonucleoside-diphosphate reductase 2 subunit alpha P39452 RIR3_ECOLI nrdE http://ecmdb.ca/proteins/P39452.xml Ribonucleoside-diphosphate reductase 1 subunit beta P69924 RIR2_ECOLI nrdB http://ecmdb.ca/proteins/P69924.xml 2'-Deoxyribonucleoside diphosphate + Thioredoxin disulfide + Water <> Ribonucleoside diphosphate + Thioredoxin R04294 Thioredoxin + NADP + Thioredoxin <> Thioredoxin disulfide + NADPH + Hydrogen ion + Thioredoxin disulfide R02016 Peptide-L-methionine + Thioredoxin disulfide + Water <> Peptide-L-methionine (R)-S-oxide + Thioredoxin R07607 Thioredoxin + Phosphoadenosine phosphosulfate + Thioredoxin disulfide <> Thioredoxin disulfide + Sulfite + Adenosine 3',5'-diphosphate + Thioredoxin R02021 Peptide-L-methionine + Thioredoxin disulfide + Water + L-Methionine <> Peptide-L-methionine (S)-S-oxide + Thioredoxin + L-methionine (S)-S-oxide R04120 2'-Deoxyribonucleoside triphosphate + Thioredoxin disulfide + Water <> Ribonucleoside triphosphate + Thioredoxin R04315 dADP + Thioredoxin disulfide + Water <> Thioredoxin + ADP Thioredoxin + Phosphoadenosine phosphosulfate + Thioredoxin disulfide <> Sulfite + Adenosine 3',5'-diphosphate dATP + Thioredoxin disulfide + Water <> Adenosine triphosphate + Thioredoxin dGTP + Thioredoxin disulfide + Water <> Guanosine triphosphate + Thioredoxin Thioredoxin + NADP <> Thioredoxin disulfide + NADPH + Hydrogen ion Peptide-L-methionine + Thioredoxin disulfide + Water <> Peptide-L-methionine (R)-S-oxide + Thioredoxin Peptide-L-methionine + Thioredoxin disulfide + Water + L-Methionine <> Peptide-L-methionine (S)-S-oxide + Thioredoxin + L-methionine (S)-S-oxide dADP + Thioredoxin disulfide + Water <> Thioredoxin + ADP Peptide-L-methionine + Thioredoxin disulfide + Water + L-Methionine <> Peptide-L-methionine (S)-S-oxide + Thioredoxin + L-methionine (S)-S-oxide