2.0 2012-05-31 10:22:38 -0600 2015-09-13 12:56:06 -0600 ECMDB00165 M2MDB000067 L-Homocysteine Homocysteine is a thiol-containing amino acid formed by a demethylation of methionine. Homocysteine is a variant of the amino acid cysteine, differing in that its side-chain contains an additional methylene (-CH2-) group before the thiol (-SH) group. In Escherichia coli homocysteine (Hcy) is the last intermediate on the methionine biosynthetic pathway. (+-)-homocysteine (S)-2-amino-4-mercapto-Butanoate (S)-2-amino-4-mercapto-Butanoic acid (S)-2-Amino-4-mercaptobutanoate (S)-2-Amino-4-mercaptobutanoic acid (S)-Homocysteine 2-amino-4-mercapto-Butanoate 2-amino-4-mercapto-Butanoic acid 2-Amino-4-mercapto-Butyrate 2-Amino-4-mercapto-Butyric acid 2-amino-4-mercapto-DL-Butyrate 2-amino-4-mercapto-DL-Butyric acid 2-Amino-4-mercapto-L-butyrate 2-Amino-4-mercapto-L-butyric acid 2-Amino-4-mercaptobutyrate 2-Amino-4-mercaptobutyric acid 2-amino-4-sulfanylbutanoate 2-amino-4-sulfanylbutanoic acid 2-amino-4-Sulphanylbutanoate 2-amino-4-Sulphanylbutanoic acid D,l-homocysteine DL-2-amino-4-mercapto-Butyrate DL-2-amino-4-mercapto-Butyric acid DL-2-amino-4-Mercaptobutyrate DL-2-Amino-4-mercaptobutyric acid DL-Homocysteine DL-homocysteine (free base) HCY Homo-cys Homocysteine L-2-Amino-4-mercapto-Butyrate L-2-Amino-4-mercapto-Butyric acid L-2-Amino-4-mercaptobutyrate L-2-Amino-4-mercaptobutyric acid L-Homocysteine Usaf B-12 C4H9NO2S 135.185 135.035399227 (2S)-2-amino-4-sulfanylbutanoic acid L-homocysteine 6027-13-0 N[C@@H](CCS)C(O)=O InChI=1S/C4H9NO2S/c5-3(1-2-8)4(6)7/h3,8H,1-2,5H2,(H,6,7)/t3-/m0/s1 FFFHZYDWPBMWHY-VKHMYHEASA-N Solid Cytosol logp -2.29 ALOGPS logs -0.96 ALOGPS solubility 1.48e+01 g/l ALOGPS melting_point 232.6 oC logp -2.6 ChemAxon pka_strongest_acidic 2.46 ChemAxon pka_strongest_basic 9.41 ChemAxon iupac (2S)-2-amino-4-sulfanylbutanoic acid ChemAxon average_mass 135.185 ChemAxon mono_mass 135.035399227 ChemAxon smiles N[C@@H](CCS)C(O)=O ChemAxon formula C4H9NO2S ChemAxon inchi InChI=1S/C4H9NO2S/c5-3(1-2-8)4(6)7/h3,8H,1-2,5H2,(H,6,7)/t3-/m0/s1 ChemAxon inchikey FFFHZYDWPBMWHY-VKHMYHEASA-N ChemAxon polar_surface_area 63.32 ChemAxon refractivity 32.93 ChemAxon polarizability 13.54 ChemAxon rotatable_bond_count 3 ChemAxon acceptor_count 3 ChemAxon donor_count 3 ChemAxon physiological_charge 0 ChemAxon formal_charge 0 ChemAxon Nitrogen 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. PW000755 ec00910 Metabolic Cysteine and methionine metabolism ec00270 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 One carbon pool by folate Dihydrofolic acid, a product of the folate biosynthesis pathway, can be metabolized by multiple enzymes. Dihydrofolic acid can be reduced by a NADP-driven dihydrofolate reductase resulting in a NADPH, hydrogen ion and folic acid. Dihydrofolic acid can also be reduced by an NADPH-driven dihydrofolate reductase resulting in a NADP and a tetrahydrofolic acid. Folic acid can also produce a tetrahydrofolic acid through a NADPH-driven dihydrofolate reductase. Dihydrofolic acid also interacts with 5-thymidylic acid through a thymidylate synthase resulting in the release of dUMP and 5,10-methylene-THF Tetrahydrofolic acid can be converted into 5,10-methylene-THF through two different reversible reactions. Tetrahydrofolic acid interacts with a S-Aminomethyldihydrolipoylprotein through a aminomethyltransferase resulting in the release of ammonia, a dihydrolipoylprotein and 5,10-Methylene-THF Tetrahydrofolic acid interacts with L-serine through a glycine hydroxymethyltransferase resulting in a glycine, water and 5,10-Methylene-THF. The compound 5,10-methylene-THF reacts with an NADPH dependent methylenetetrahydrofolate reductase [NAD(P)H] resulting in NADP and 5-Methyltetrahydrofolic acid. This compound interacts with homocysteine through a methionine synthase resulting in L-methionine and tetrahydrofolic acid. Tetrahydrofolic acid can be metabolized into 10-formyltetrahydrofolate through 4 different enzymes: 1.- Tetrahydrofolic acid interacts with FAICAR through a phosphoribosylaminoimidazolecarboxamide formyltransferase resulting in a 1-(5'-Phosphoribosyl)-5-amino-4-imidazolecarboxamide and a 10-formyltetrahydrofolate 2.-Tetrahydrofolic acid interacts with 5'-Phosphoribosyl-N-formylglycinamide through a phosphoribosylglycinamide formyltransferase 2 resulting in a Glycineamideribotide and a 10-formyltetrahydrofolate 3.-Tetrahydrofolic acid interacts with Formic acid through a formyltetrahydrofolate hydrolase resulting in water and a 10-formyltetrahydrofolate 4.-Tetrahydrofolic acid interacts with N-formylmethionyl-tRNA(fMet) through a 10-formyltetrahydrofolate:L-methionyl-tRNA(fMet) N-formyltransferase resulting in a L-methionyl-tRNA(Met) and a 10-formyltetrahydrofolate 10-formyltetrahydrofolate can interact with a hydrogen ion through a bifunctional 5,10-methylene-tetrahydrofolate dehydrogenase resulting in water and 5,10-methenyltetrahydrofolic acid. Tetrahydrofolic acid can be metabolized into 5,10-methenyltetrahydrofolic acid by reacting with a 5'-phosphoribosyl-a-N-formylglycineamidine through a phosphoribosylglycinamide formyltransferase 2 resulting in water, glycineamideribotide and 5,10-methenyltetrahydrofolic acid. The latter compound can either interact with water through an aminomethyltransferase resulting in a N5-Formyl-THF, or it can interact with a NADPH driven bifunctional 5,10-methylene-tetrahydrofolate dehydrogenase resulting in a NADP and 5,10-Methylene THF. PW000773 ec00670 Metabolic Metabolic pathways eco01100 <i>S</i>-adenosyl-L-methionine cycle I PWY-6151 autoinducer AI-2 biosynthesis I PWY-6153 formylTHF biosynthesis I 1CMET2-PWY methionine biosynthesis I HOMOSER-METSYN-PWY Specdb::CMs 3134 Specdb::CMs 30370 Specdb::CMs 147699 Specdb::CMs 1074587 Specdb::CMs 1074589 Specdb::CMs 1074590 Specdb::CMs 1074592 Specdb::CMs 1074594 Specdb::CMs 1074595 Specdb::NmrOneD 5208 Specdb::NmrOneD 5209 Specdb::NmrOneD 5210 Specdb::NmrOneD 5211 Specdb::NmrOneD 145170 Specdb::NmrOneD 145171 Specdb::NmrOneD 145172 Specdb::NmrOneD 145173 Specdb::NmrOneD 145174 Specdb::NmrOneD 145175 Specdb::NmrOneD 145176 Specdb::NmrOneD 145177 Specdb::NmrOneD 145178 Specdb::NmrOneD 145179 Specdb::NmrOneD 145180 Specdb::NmrOneD 145181 Specdb::NmrOneD 145182 Specdb::NmrOneD 145183 Specdb::NmrOneD 145184 Specdb::NmrOneD 145185 Specdb::NmrOneD 145186 Specdb::NmrOneD 145187 Specdb::NmrOneD 145188 Specdb::NmrOneD 145189 Specdb::MsMs 25745 Specdb::MsMs 25746 Specdb::MsMs 25747 Specdb::MsMs 32303 Specdb::MsMs 32304 Specdb::MsMs 32305 Specdb::MsMs 447603 Specdb::MsMs 447753 Specdb::MsMs 447754 Specdb::MsMs 2255806 Specdb::MsMs 2262739 Specdb::MsMs 2262740 Specdb::MsMs 2262741 Specdb::MsMs 3080268 Specdb::MsMs 3080269 Specdb::MsMs 3080270 Specdb::NmrTwoD 2041 HMDB00742 82666 C00155 17588 HOMO-CYS HCS Homocysteine Keseler, 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. 21097882 Kanehisa, 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. 22080510 Vijayendran, C., Barsch, A., Friehs, K., Niehaus, K., Becker, A., Flaschel, E. (2008). "Perceiving molecular evolution processes in Escherichia coli by comprehensive metabolite and gene expression profiling." Genome Biol 9:R72. 18402659 van 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. 17765195 Winder, 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. 18331064 Bennett, B. D., Kimball, E. H., Gao, M., Osterhout, R., Van Dien, S. J., Rabinowitz, J. D. (2009). "Absolute metabolite concentrations and implied enzyme active site occupancy in Escherichia coli." Nat Chem Biol 5:593-599. 19561621 Biochem Prepn. 5 93 (1957) http://hmdb.ca/system/metabolites/msds/000/000/661/original/HMDB00742.pdf?1358461574 Cystathionine gamma-synthase P00935 METB_ECOLI metB http://ecmdb.ca/proteins/P00935.xml Cystathionine beta-lyase metC P06721 METC_ECOLI metC http://ecmdb.ca/proteins/P06721.xml Methionine synthase P13009 METH_ECOLI metH http://ecmdb.ca/proteins/P13009.xml Protein malY P23256 MALY_ECOLI malY http://ecmdb.ca/proteins/P23256.xml 5-methyltetrahydropteroyltriglutamate--homocysteine methyltransferase P25665 METE_ECOLI metE http://ecmdb.ca/proteins/P25665.xml S-ribosylhomocysteine lyase P45578 LUXS_ECOLI luxS http://ecmdb.ca/proteins/P45578.xml Homocysteine S-methyltransferase Q47690 MMUM_ECOLI mmuM http://ecmdb.ca/proteins/Q47690.xml L-Cystathionine + Water > L-Homocysteine + Ammonium + Pyruvic acid 5-Methyltetrahydrofolic acid + L-Homocysteine <> Hydrogen ion + L-Methionine + Tetrahydrofolic acid R00946 HOMOCYSMETB12-RXN L-Homocysteine + S-Methylmethionine > Hydrogen ion +2 L-Methionine S-Adenosylmethionine + L-Homocysteine + S-Methylmethionine <> S-Adenosylhomocysteine + Hydrogen ion + L-Methionine R00650 HOMOCYSTEINE-S-METHYLTRANSFERASE-RXN S-Ribosyl-L-homocysteine > 4,5-Dihydroxy-2,3-pentanedione + L-Homocysteine RIBOSYLHOMOCYSTEINASE-RXN S-Adenosylmethionine + L-Homocysteine <> S-Adenosylhomocysteine + L-Methionine R00650 HOMOCYSTEINE-S-METHYLTRANSFERASE-RXN 5-Methyltetrahydrofolic acid + L-Homocysteine <> Tetrahydrofolic acid + L-Methionine R00946 Cystathionine + Water <> L-Homocysteine + Ammonia + Pyruvic acid R01285 L-Cystathionine + Water <> L-Homocysteine + Ammonia + Pyruvic acid R01286 O-Succinyl-L-homoserine + Hydrogen sulfide <> L-Homocysteine + Succinic acid R01288 S-Ribosyl-L-homocysteine <> (4S)-4,5-Dihydroxypentan-2,3-dione + L-Homocysteine R01291 5-Methyltetrahydropteroyltri-L-glutamic acid + L-Homocysteine <> Tetrahydropteroyltri-L-glutamic acid + L-Methionine R04405 L-Cystathionine + Water > Hydrogen ion + Pyruvic acid + Ammonia + L-Homocysteine R01286 CYSTATHIONINE-BETA-LYASE-RXN L-Homocysteine + 5-Methyltetrahydropteroyltri-L-glutamic acid > L-Methionine + tetrahydropteroyl tri-L-glutamate HOMOCYSMET-RXN L-Homocysteine + 5-Methyltetrahydrofolic acid L-Methionine + Tetrahydrofolic acid HOMOCYSMETB12-RXN L-Homocysteine + S-Adenosylmethionine Hydrogen ion + L-Methionine + S-Adenosylhomocysteine HOMOCYSTEINE-S-METHYLTRANSFERASE-RXN S-methyl-L-methionine + L-Homocysteine Hydrogen ion + L-Methionine MMUM-RXN S-Ribosyl-L-homocysteine > L-Homocysteine + (4S)-4,5-Dihydroxypentan-2,3-dione L-Cystathionine + Water > L-Homocysteine + Ammonia + Pyruvic acid 5-methyltetrahydropteroyltri-L-glutamate + L-Homocysteine > tetrahydropteroyltri-L-glutamate + L-Methionine 5-Methyltetrahydrofolic acid + L-Homocysteine > Tetrahydrofolic acid + L-Methionine S-methyl-L-methionine + L-Homocysteine >2 L-Methionine L-Cystathionine + Water + 2-Aminoacrylic acid + 2-Iminopropanoate <> L-Homocysteine + Pyruvic acid + Ammonia R01286 5 5-Methyltetrahydrofolic acid + L-Homocysteine <> Hydrogen ion + L-Methionine + Tetrahydrofolic acid 5 5-Methyltetrahydrofolic acid + L-Homocysteine <> Hydrogen ion + L-Methionine + Tetrahydrofolic acid Gutnick minimal complete medium (4.7 g/L KH2PO4; 13.5 g/L K2HPO4; 1 g/L K2SO4; 0.1 g/L MgSO4-7H2O; 10 mM NH4Cl) with 4 g/L glucose Shake flask and filter culture 370.0 uM 0.0 37 oC K12 NCM3722 Mid-Log Phase 1480000 0 Bennett, B. D., Kimball, E. H., Gao, M., Osterhout, R., Van Dien, S. J., Rabinowitz, J. D. (2009). "Absolute metabolite concentrations and implied enzyme active site occupancy in Escherichia coli." Nat Chem Biol 5:593-599. 19561621