2.0 2015-09-08 17:48:45 -0600 2015-09-08 17:48:45 -0600 ECMDB24053 M2MDB006170 Homocysteine C4H9NO2S 135.185 135.035399227 2-amino-4-sulfanylbutanoic acid homocysteine NC(CCS)C(O)=O InChI=1S/C4H9NO2S/c5-3(1-2-8)4(6)7/h3,8H,1-2,5H2,(H,6,7) FFFHZYDWPBMWHY-UHFFFAOYSA-N logp -2.29 ALOGPS logs -0.96 ALOGPS solubility 1.48e+01 g/l ALOGPS logp -2.6 ChemAxon pka_strongest_acidic 2.46 ChemAxon pka_strongest_basic 9.41 ChemAxon iupac 2-amino-4-sulfanylbutanoic acid ChemAxon average_mass 135.185 ChemAxon mono_mass 135.035399227 ChemAxon smiles NC(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) ChemAxon inchikey FFFHZYDWPBMWHY-UHFFFAOYSA-N ChemAxon polar_surface_area 63.32 ChemAxon refractivity 32.94 ChemAxon polarizability 13.44 ChemAxon rotatable_bond_count 3 ChemAxon acceptor_count 3 ChemAxon donor_count 3 ChemAxon physiological_charge 0 ChemAxon formal_charge 0 ChemAxon One Carbon Pool by Folate I 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. PW001735 Metabolic Quorum Sensing Bacterial Autoinducer 2 (AI-2) mediates the quorum sensing 2 system. AI-2 is catalyzed by the luxS enzyme. This enzyme is found in E.coli and S.typhimurium. In E. coli and most pathogenic bacteria that form AI-2 are spontaneous transformations that include cyclization to (2R,4S)-2-methyl-2,4-dihydroxydihydrofuran-3-one and hydration to the final autoinducer (2R,4S)-2-methyl-2,3,3,4-tetrahydroxytetrahydrofuran. This product is released from the cell through the AI-2 transporter (tqsA). As the level of AI-2 increases, other cells detect it and import it through the autoinducer-2 ABC transporter (lsrACDB). AI-2 is then degraded in the cells by phosphorylating the AI-2 which is then isomerized to P-HPD which follows by the transfer of and acetyl group to coenzyme A and releases dihydroxyacetone phosphate PW000836 Signaling methionine biosynthesis The de novo biosynthesis of methionine is an energy-costly process involving inputs from several other pathways. The carbon skeleton of methionine is derived from aspartate. The sulfur is derived from cysteine which derives its sulfur from sulfate assimilation. The methyl group is derived from serine via one-carbon metabolism. Methionine is also converted to S-adenosyl-L-methionine, a methyl group donor, by the product of gene metK . The synthesis starts with a product of the lysine biosynthesis pathway, L-aspartate-semialdehyde. This compound is dehydrogenated by a NADPH aspartate kinase / homoserine dehydrogenase resulting in NADP and L-homoserine. Homoserine is activated by O-succinylation in a reaction catalyzed by MetA. The product O-succinyl-L-homoserine combines with cysteine to form cystathionine in a reaction catalyzed by MetB. Lyase cleavage of cystathionine by MetC forms homocysteine. This β-cystathionase activity can also be supplied by MalY as demonstrated in vivo by the ability of constitutive MalY expression to complement metC mutants auxotrophic for methionine . Homocysteine is subsequently methylated by either MetH or MetE to produce methionine. In E. coli MetH can function only in the presence of exogenously supplied vitamin B12 (cobalamin), which represses MetE expression. B12 is likely to be available in the gut. In the absence of exogenously supplied B12, MetE catalyzes this final step of de novo methionine biosynthesis. L-methionine is then transferred into the periplasmic space through a leucine efflux transporter. Under stressful conditions there is further regulation of the pathway enzymes. Under heat-shock conditions growth is slowed due to the thermal instability of MetA. Oxidative stress affects MetE which contains an oxidation-sensitive cysteine residue at position 645 near the active site. Oxidation of methionone itself can also occur although the cell contains methionine sufloxide reductases MsrA and MsrB to combat this. Weak organic acids also generate oxidative stress, with more complex effects. Sulfur limitation depletes homocysteine which serves as a coactivator for MetR activation of MetE expression. Due to the absence of this pathway in mammals, some of the bacterial biosynthetic enzymes are potential drug targets. In addition, although methionine is used as a food additive and a medication, its industrial scale production in microorganisms has not yet been achieved due to the complexity and strong regulation of its biosynthetic pathway. PW000814 Metabolic S-adenosyl-L-methionine cycle The S-adenosyl-L-methionine cycle starts with S-adenosyl-L-methionine reacting with (a demethylated methyl donor ) dimethylglycine resulting in the release of a hydrogen ion, a betain (a methylated methyl donor) and a S-adenosyl-L-homocysteine. The s-adenosyl-L-homocysteine reacts with a water molecule through a S-adenosylhomocysteine nucleosidase resulting in the release of a adenine and a ribosyl-L-homocysteine. This compound in turn reacts with a s-ribosylhomocysteine lyase resulting in the release of a l-homocysteine and a autoinducer 2. The L-homocysteine reacts with a N5-methyl-tetrahydropteroyl tri-L-glutamate through a methionine synthase resulting in the release of a tetrahydropteroyl tri-L-glutamate and a methione. The methionine in turn reacts with a water molecule and ATP molecule through a methionine adenosyltransferase resulting in the release of a diphosphate, a phosphate and a s-adenosyl-L-methionine. PW002080 Metabolic Specdb::CMs 630 Specdb::CMs 631 Specdb::CMs 632 Specdb::CMs 633 Specdb::CMs 1273 Specdb::CMs 1329 Specdb::CMs 3339 Specdb::CMs 30049 Specdb::CMs 30522 Specdb::CMs 30839 Specdb::CMs 31216 Specdb::CMs 31217 Specdb::CMs 37735 Specdb::NmrOneD 1513 Specdb::NmrOneD 2390 Specdb::NmrOneD 4868 Specdb::NmrOneD 4869 Specdb::NmrOneD 270098 Specdb::NmrOneD 270099 Specdb::NmrOneD 270100 Specdb::NmrOneD 270101 Specdb::NmrOneD 270102 Specdb::NmrOneD 270103 Specdb::NmrOneD 270104 Specdb::NmrOneD 270105 Specdb::NmrOneD 270106 Specdb::NmrOneD 270107 Specdb::NmrOneD 270108 Specdb::NmrOneD 270109 Specdb::NmrOneD 270110 Specdb::NmrOneD 270111 Specdb::NmrOneD 270112 Specdb::NmrOneD 270113 Specdb::NmrOneD 270114 Specdb::NmrOneD 270115 Specdb::NmrOneD 270116 Specdb::NmrOneD 270117 Specdb::MsMs 1053 Specdb::MsMs 1054 Specdb::MsMs 1055 Specdb::MsMs 179949 Specdb::MsMs 179950 Specdb::MsMs 179951 Specdb::MsMs 182283 Specdb::MsMs 182284 Specdb::MsMs 182285 Specdb::NmrTwoD 1459 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 5-Methyltetrahydrofolic acid + Homocysteine + 5-Methyltetrahydrofolic acid + Homocysteine > Tetrahydrofolic acid + L-Methionine + Tetrahydrofolic acid PW_R002542 Homocysteine + N5-methyl--tetrahydropteroyl tri-L-glutamate + Homocysteine > L-Methionine + tetrahydropteroyltri-L-glutamate PW_R002893 L-Cystathionine > Hydrogen ion + Homocysteine + 2-aminoprop-2-enoate + Homocysteine PW_R002891 Homocysteine + N5-methyl--tetrahydropteroyl tri-L-glutamate + Homocysteine > tetrahydropteroyltri-L-glutamate + L-Methionine PW_R002892 S-ribosyl-L-homocysteine + S-ribosyl-L-homocysteine > Homocysteine + autoinducer 2 + Homocysteine + autoinducer 2 PW_R003068 Homocysteine + S-Methylmethionine <>2 L-Methionine + Hydrogen ion PW_R005874 S-ribosyl-L-homocysteine > 4,5-Dihydroxy-2,3-pentanedione + Homocysteine PW_R005929