2.0 2012-05-31 13:00:34 -0600 2015-09-13 12:56:08 -0600 ECMDB00696 M2MDB000175 L-Methionine L-Methionine, in addition to being a substrate for protein synthesis, is an intermediate in transmethylation reactions, serving as the major methyl group donor, including the methyl groups for DNA and RNA intermediates. Methionine is a methyl acceptor for 5-methyltetrahydrofolate-homocysteine methyl transferase (methionine synthase), the only reaction that allows for the recycling of this form of folate, and is also a methyl acceptor for the catabolism of betaine. Methionine is also required for synthesis of cysteine. Methionine is accepted as the metabolic precursor for cysteine. Only the sulfur atom from methionine is transferred to cysteine; the carbon skeleton of cysteine is donated by serine. (PMID 16702340) (2S)-2-amino-4-(methylsulfanyl)butanoate (2S)-2-amino-4-(methylsulfanyl)butanoic acid (2S)-2-amino-4-(methylsulphanyl)butanoate (2S)-2-amino-4-(methylsulphanyl)butanoic acid (L)-methionine (S)-(+)-methionine (S)-2-amino-4-(methylthio)-Butanoate (S)-2-amino-4-(methylthio)-Butanoic acid (S)-2-Amino-4-(methylthio)butanoate (S)-2-Amino-4-(methylthio)butanoic acid (S)-2-amino-4-(methylthio)butyrate (S)-2-amino-4-(methylthio)butyric acid (S)-methionine 2-Amino-4-(methylthio)butyrate 2-Amino-4-(methylthio)butyric acid 2-Amino-4-methylthiobutanoate 2-Amino-4-methylthiobutanoic acid a-amino-a-Aminobutyrate a-amino-a-Aminobutyric acid A-Amino-g-methylmercaptobutyrate A-Amino-g-methylmercaptobutyric acid Acimethin Alpha-Amino-alpha-aminobutyrate Alpha-Amino-alpha-aminobutyric acid Alpha-Amino-gamma-methylmercaptobutyrate Alpha-Amino-gamma-methylmercaptobutyric acid Cymethion G-Methylthio-a-aminobutyrate G-Methylthio-a-aminobutyric acid Gamma-Methylthio-alpha-aminobutyrate Gamma-Methylthio-alpha-aminobutyric acid H-Met-h H-Met-oh L(-)-amino-a-amino-a-Aminobutyrate L(-)-amino-a-amino-a-Aminobutyric acid L(-)-Amino-alpha-amino-alpha-aminobutyrate L(-)-Amino-alpha-amino-alpha-aminobutyric acid L(-)-amino-g-Methylthiobutyrate L(-)-amino-g-Methylthiobutyric acid L(-)-Amino-gamma-methylthiobutyrate L(-)-Amino-gamma-methylthiobutyric acid L(-)-amino-α-amino-α-Aminobutyrate L(-)-amino-α-amino-α-Aminobutyric acid L(-)-amino-γ-Methylthiobutyrate L(-)-amino-γ-Methylthiobutyric acid L-(-)-Methionine L-2-Amino-4-(methylthio)butyrate L-2-Amino-4-(methylthio)butyric acid L-2-amino-4-Methylthiobutyrate L-2-Amino-4-methylthiobutyric acid L-2-Amino-4methylthiobutyrate L-2-Amino-4methylthiobutyric acid L-a-amino-g-Methylmercaptobutyrate L-a-amino-g-Methylmercaptobutyric acid L-a-Amino-g-methylthiobutyrate L-a-Amino-g-methylthiobutyric acid L-alpha-Amino-gamma-methylmercaptobutyrate L-alpha-Amino-gamma-methylmercaptobutyric acid L-alpha-Amino-gamma-methylthiobutyrate L-alpha-Amino-gamma-methylthiobutyric acid L-g-methylthio-a-Aminobutyrate L-g-methylthio-a-Aminobutyric acid L-gamma-Methylthio-alpha-aminobutyrate L-gamma-Methylthio-alpha-aminobutyric acid L-Methionin L-Methionine L-Methioninum L-α-amino-γ-Methylmercaptobutyrate L-α-amino-γ-Methylmercaptobutyric acid L-α-amino-γ-Methylthiobutyrate L-α-amino-γ-Methylthiobutyric acid L-γ-methylthio-α-Aminobutyrate L-γ-methylthio-α-Aminobutyric acid Liquimeth M Mepron MET Methilanin Methionine Methioninum Metionina Neo-methidin Poly-L-methionine Polymethionine S-Methionine S-Methyl-L-homocysteine Toxin WAR α-amino-α-Aminobutyrate α-amino-α-Aminobutyric acid α-amino-γ-Methylmercaptobutyrate α-amino-γ-Methylmercaptobutyric acid γ-methylthio-α-Aminobutyrate γ-methylthio-α-Aminobutyric acid C5H11NO2S 149.211 149.051049291 (2S)-2-amino-4-(methylsulfanyl)butanoic acid L-methionine 63-68-3 CSCC[C@H](N)C(O)=O InChI=1S/C5H11NO2S/c1-9-3-2-4(6)5(7)8/h4H,2-3,6H2,1H3,(H,7,8)/t4-/m0/s1 FFEARJCKVFRZRR-BYPYZUCNSA-N Solid Cytosol Extra-organism Periplasm logp -1.85 ALOGPS logs -0.80 ALOGPS solubility 2.39e+01 g/l ALOGPS melting_point 284 oC logp -2.2 ChemAxon pka_strongest_acidic 2.53 ChemAxon pka_strongest_basic 9.5 ChemAxon iupac (2S)-2-amino-4-(methylsulfanyl)butanoic acid ChemAxon average_mass 149.211 ChemAxon mono_mass 149.051049291 ChemAxon smiles CSCC[C@H](N)C(O)=O ChemAxon formula C5H11NO2S ChemAxon inchi InChI=1S/C5H11NO2S/c1-9-3-2-4(6)5(7)8/h4H,2-3,6H2,1H3,(H,7,8)/t4-/m0/s1 ChemAxon inchikey FFEARJCKVFRZRR-BYPYZUCNSA-N ChemAxon polar_surface_area 63.32 ChemAxon refractivity 37.59 ChemAxon polarizability 15.5 ChemAxon rotatable_bond_count 4 ChemAxon acceptor_count 3 ChemAxon donor_count 2 ChemAxon physiological_charge 0 ChemAxon formal_charge 0 ChemAxon Cysteine and methionine metabolism ec00270 Selenoamino acid metabolism ec00450 Aminoacyl-tRNA biosynthesis ec00970 Porphyrin and chlorophyll metabolism ec00860 Biotin metabolism Biotin (vitamin H or vitamin B7) is the essential cofactor of biotin-dependent carboxylases, such as pyruvate carboxylase and acetyl-CoA carboxylase.In E. coli and many organisms, pimelate thioester is derived from malonyl-ACP. The pathway starts with a malonyl-[acp] interacting with S-adenosylmethionine through a biotin synthesis protein BioC resulting in a S-adenosylhomocysteine and a malonyl-[acp] methyl ester. The latter compound is then involved in the synthesis of a 3-ketoglutaryl-[acp] methyl ester through a 3-oxoacyl-[acyl-carrier-protein] synthase. The compound 3-ketoglutaryl-[acp] methyl ester is reduced by a NADPH mediated 3-oxoacyl-[acyl-carrier-protein] reductase resulting in a 3R-hydroxyglutaryl-[acp] methyl ester. This compound is then dehydrated through ad (3R)-hydroxymyristoyl-[acp] dehydratase producing a enoylglutaryl-[acp] methyl ester. This compound is then reduced through a NADPH mediated enoyl-acp-reductase [NADH] resulting in a glutaryl-[acp] methyl ester. This compound interacts with a malonyl-[acp] through a 3-oxoacyl-[acp] synthase 2 resulting in a 3-ketopimeloyl [acp] methyl ester. This compound is then reduced through a NADPH 3-oxoacyl [acp] reductase producing a 3-hydroxypimeloyl-[acp] methyl ester and then dehydrated by (3R)-hydroxymyristoyl-[acp] dehydratase to produce a enoylpimeloyl-[acp] methyl ester. This compound is then reduced by a NADPH dependent enoyl-[acp]reductase resulting in a pimeloyl-[acp] methyl ester. This compound then reacts with water through a carboxylesterase resulting in a pimeloyl-[acp] and a methanol. The pimeloyl-acp reacts with L-alanine through a 8-amino-7-oxononanoate synthase resulting in 8-amino-7-oxononanoate which in turn reacts with S-adenosylmethionine through a 7,8 diaminonanoate transaminase resulting in a S-adenosyl-4-methylthio-2-oxobutanoate and 7,8 diaminononanoate. The latter compound is then dephosphorylated through a dethiobiotin synthetase resulting in a dethiobiotin. This compound interacts with a sulfurated[sulfur carrier), a hydrogen ion and a S-adenosylmethionine through a biotin synthase to produce Biotin and releasing l-methionine and a 5-deoxyadenosine. Biotin is then metabolized by a bifunctional protein resulting in pyrophosphate and Biotinyl-5-AMP which in turn reacts with the same protein (bifunctional protein birA resulting ina biotin caroxyl carrying protein.This product then enters the fatty acid biosynthesis. PW000762 ec00780 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 Thiamine metabolism ec00730 Lipoic acid metabolism Lipoic acid metabolism starts with caprylic acid being introduced into the cytoplasm however no transporter has been identified yet. Once caprylic acid is in the cytoplasm, it can either reacts with a holo-acp, through an ATP driven 2-acylglycerophosphoethanolamine acyltransferase / acyl-ACP synthetase resulting in pyrophosphate, AMP and octanoyl-[acp]. The latter compound can also be obtained from palmitate biosynthesis. Octanoyl-acp interacts with a lipoyl-carrier protein L-lysine through a Octanoyltransferase resulting in a hydrogen ion, a holo-acyl-acp, and a protein N6-0octanoyl) lysine. The latter compound reacts with an S-adenosylmethionine, a sulfurated[sulfur carrier] and a reduced ferredoxin through a lipoate-protein ligase A, resulting in a 5-deoxyadenosine, a L-methionine, an unsulfurated [sulfur carrier], oxidized ferredoxin, and a Protein N6-(lipoyl) lysine. Caprylic acid can also interact with ATP and a lipoyl-carrier protein-L-lysine through a lipoate-protein ligase A resulting in a amp, pyrophosphate, hydrogen ion, protein N6-(octanoyl)lysine. The latter compound reacts with an S-adenosylmethionine, a sulfurated[sulfur carrier] and a reduced ferredoxin through a lipoate-protein ligase A, resulting in a 5-deoxyadenosine, a L-methionine, an unsulfurated [sulfur carrier], oxidized ferredoxin, and a Protein N6-(lipoyl) lysine. R-lipoic acid can be absorbed from the environment, as seen in studies by Morris TW. In this pathway the lipoyl-protein ligase LplA utilizes pre-existing lipoate that has been imported from outside the cell, and thus catalyzes a salvage pathway. Lipoic acid interacts with ATP and hydrogen ion through a lipoyl-protein ligase A, resulting in a pyrophosphate and a Lipoyl-AMP (lipoyl-adenylate). This compound then interacts with a lipoyl-carrier protein-L-lysine through a lipoate-protein ligase A resulting a AMP, a hydrogen ion and a Protein N6-(lipoyl) lysine. It has been suggested that the conversion of octanoylated-domains to lipoylated ones described in this pathway may be a type of a repair pathway, activated only if the other lipoate biosynthetic pathways are malfunctioning . PW000770 ec00785 Metabolic Metabolic pathways eco01100 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 Porphyrin metabolism The metabolism of porphyrin begins with with glutamic acid being processed by an ATP-driven glutamyl-tRNA synthetase by interacting with hydrogen ion and tRNA(Glu), resulting in amo, pyrophosphate and L-glutamyl-tRNA(Glu) Glutamic acid. Glutamic acid can be obtained as a result of L-glutamate metabolism pathway, glutamate / aspartate : H+ symporter GltP, glutamate:sodium symporter or a glutamate / aspartate ABC transporter . L-glutamyl-tRNA(Glu) Glutamic acid interacts with a NADPH glutamyl-tRNA reductase resulting in a NADP, a tRNA(Glu) and a (S)-4-amino-5-oxopentanoate. This compound interacts with a glutamate-1-semialdehyde aminotransferase resulting a 5-aminolevulinic acid. This compound interacts with a porphobilinogen synthase resulting in a hydrogen ion, water and porphobilinogen. The latter compound interacts with water resulting in hydroxymethylbilane synthase resulting in ammonium, and hydroxymethylbilane. Hydroxymethylbilane can either be dehydrated to produce uroporphyrinogen I or interact with a uroporphyrinogen III synthase resulting in a water molecule and a uroporphyrinogen III. Uroporphyrinogen I interacts with hydrogen ion through a uroporphyrinogen decarboxylase resulting in a carbon dioxide and a coproporphyrinogen I Uroporphyrinogen III can be metabolized into precorrin by interacting with a S-adenosylmethionine through a siroheme synthase resulting in hydrogen ion, an s-adenosylhomocysteine and a precorrin-1. On the other hand, Uroporphyrinogen III interacts with hydrogen ion through a uroporphyrinogen decarboxylase resulting in a carbon dioxide and a Coproporphyrinogen III. Precorrin-1 reacts with a S-adenosylmethionine through a siroheme synthase resulting in a S-adenosylhomocysteine and a Precorrin-2. The latter compound is processed by a NAD dependent uroporphyrin III C-methyltransferase [multifunctional] resulting in a NADH and a sirohydrochlorin. This compound then interacts with Fe 2+ uroporphyrin III C-methyltransferase [multifunctional] resulting in a hydrogen ion and a siroheme. The siroheme is then processed in sulfur metabolism pathway. Uroporphyrinogen III can be processed in anaerobic or aerobic condition. Anaerobic: Uroporphyrinogen III interacts with an oxygen molecule, a hydrogen ion through a coproporphyrinogen III oxidase resulting in water, carbon dioxide and protoporphyrinogen IX. The latter compound then interacts with an 3 oxygen molecule through a protoporphyrinogen oxidase resulting in 3 hydrogen peroxide and a Protoporphyrin IX Aerobic: Uroporphyrinogen III reacts with S-adenosylmethionine through a coproporphyrinogen III dehydrogenase resulting in carbon dioxide, 5-deoxyadenosine, L-methionine and protoporphyrinogen IX. The latter compound interacts with a meanquinone through a protoporphyrinogen oxidase resulting in protoporphyrin IX. The protoporphyrin IX interacts with Fe 2+ through a ferrochelatase resulting in a hydrogen ion and a ferroheme b. The ferroheme b can either be incorporated into the oxidative phosphorylation as a cofactor of the enzymes involved in that pathway or it can interact with hydrogen peroxide through a catalase HPII resulting in a heme D. Heme D can then be incorporated into the oxidative phosphyrlation pathway as a cofactor of the enzymes involved in that pathway. Ferroheme b can also interact with water and a farnesyl pyrophosphate through a heme O synthase resulting in a release of pyrophosphate and heme O. Heme O is then incorporated into the Oxidative phosphorylation pathway. PW000936 Metabolic S-adenosyl-L-methionine biosynthesis S-adenosyl-L-methionine biosynthesis(SAM) is synthesized in the cytosol of the cell from L-methionine and ATP. This reaction is catalyzed by methionine adenosyltransferase. L methione is taken up from the environment through a complex reaction coupled transport and then proceeds too synthesize the s adenosylmethionine through a adenosylmethionine synthase. The S-adenosylmethionine then interacts with a hydrogen ion through a adenosylmethionine decarboxylase resulting in a carbon dioxide and a S-adenosyl 3-methioninamine.This compound interacts with a putrescine through a spermidine synthase resulting in a spermidine, a hydrogen ion and a S-methyl-5'-thioadenosine. The latter compound is degraded by interacting with a water molecule through a 5' methylthioadenosine nucleosidase resulting in a adenine and a S-methylthioribose which is then release into the environment PW000837 Metabolic 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 preQ0 metabolism PreQ0 or 7-cyano-7-carbaguanine is biosynthesized by degrading GTP. GTP first interacts with water through a GTP cyclohydrolase resulting in the release of a formate, a hydrogen ion and a 7,8-dihydroneopterin 3'-triphosphate. The latter compound then interacts with water through a 6-carboxy-5,6,7,8-tetrahydropterin synthase resulting in a acetaldehyde, triphosphate, 2 hydrogen ion and 6-carboxy-5,6,7,8-tetrahydropterin. The latter compound then reacts spontaneously with a hydrogen ion resulting in the release of a ammonium molecule and a 7-carboxy-7-deazaguanine. This compound then interacts with ATP and ammonium through 7-cyano-7-deazaguanine synthase resulting in the release of water, phosphate, ADP, hydrogen ion and a 7-cyano-7-carbaguanine. The degradation of 7-cyano-7-deazaguanine can lead to produce a preQ1 or a queuine by reacting with 3 hydrogen ions and 2 NADPH through a 7-cyano-7-deazaguanine reductase. PreQ1 then interacts with a guanine 34 in tRNA through a tRNA-guanine transglycosylase resulting in a release of a guanine and a 7-aminomethyl-7-deazaguanosine 34 in tRNA. This nucleic acid then interacts with SAM through a S-adenosylmethionine tRNA ribosyltransferase-isomerase resulting in a release of a hydrogen ion, L-methionine, adenine and an epoxyqueuosine PW001893 Metabolic tRNA Charging 2 This pathway groups together all E. coli tRNA charging reactions. PW000803 Metabolic tRNA charging This pathway groups together all E. coli tRNA charging reactions. PW000799 Metabolic tyrosine biosynthesis The pathways of biosynthesis of phenylalaline and tyrosine are intimately connected. First step of both pathways is the conversion of chorismate to prephenate, the third step of both is the conversion of a ketoacid to the aminoacid through transamination. The two pathways differ only in the second step of their three-step reaction sequences: In the case of phenylalanine biosynthesi a dehydratase converts prephenate to phenylpyruvate(reaction occurs slowly in the absence of enzymic activity); in the case of tyrosine biosynthesis, a dehydrogenase converts prephenate to p-hydroxyphenylpyruvate. Also in both pathways the first two steps are catalyzed by two distinc active sites on a single protein. Thus the first step of each pathway can be catalyzed by two enzyme: those associated with both the phenylalanine specific dehydratase and the tyrosine specific dehydrogenase. Three enzymes those enconde by tyrB, aspC and ilvE are involved in catalyzing the third step of these pathways, all three can contribute to the synthesis of phenylalanine: only tyrB and aspC contribute to biosynthesis of tyrosine PW000806 Metabolic Thiamin diphosphate biosynthesis PW002028 Metabolic Thiazole Biosynthesis I This pathway describes only the synthesis of the thiazole moiety of thiamin. Different variations of this pathway exist, this particular pathway describes the pathway that occurs in Escherichia coli K-12 and Salmonella enterica enterica serovar Typhimurium. The biosynthesis of the thiazole moiety is complex. In Escherichia coli it involves six proteins, the products of the thiS, thiF, thiG, thiH, thiI, and iscS genes. The process begins when IscS, a protein that is also involved in the biosynthesis of iron-sulfur clusters, catalyzes the transfer of a sulfur atom from cysteine to a ThiI sulfur-carrier protein, generating a an S-sulfanyl-[ThiI sulfur-carrier protein]. In a parallel route, the ThiF protein activates a ThiS sulfur-carrier protein by adenylation of its carboxy terminus, generating a carboxy-adenylated-[ThiS sulfur-carrier protein]. In a second reaction, which may also be catalyzed by ThiF, the sulfur from an S-sulfanyl-[ThiI sulfur-carrier protein] is transferred to ThiS, generating a thiocarboxy-[ThiS-Protein]. The final reaction of this pathway, which is catalyzed by the ThiG protein, requires three inputs: a thiocarboxy-[ThiS-Protein], 1-deoxy-D-xylulose 5-phosphate and 2-iminoacetate. 2-iminoacetate is formed in Escherichia coli from L-tyrosine by tyrosine lyase (ThiH), which forms a complex with ThiG. For many years the products of this reaction was assumed to be 4-methyl-5-(β-hydroxyethyl)thiazole (thiazole). However, recent work performed with the thiazole synthase from Bacillus subtilis has shown that the actual product is the thiazole tautomer 2-[(2R,5Z)-(2-carboxy-4-methylthiazol-5(2H)-ylidene]ethyl phosphate. While in Bacillus a dedicated thiazole tautomerase converts this product into a different tautomer (2-(2-carboxy-4-methylthiazol-5-yl)ethyl phosphate), most of the proteobacteria lack the tautomerase. (EcoCyc) PW002041 Metabolic Lipoate Biosynthesis and Incorporation I The biosynthesis of lipoate is unusual, and shares the same mechanism as the biosynthesis of biotin. The first enzyme in this pathway, lipoyl(octanoyl) transferase, transfers the octanoate moiety from octanoate-ACP molecules to specific lysyl residues in lipoate-dependent enzymes, resulting in octanylated domains, and regenerating the acyl-carrier protein in the process. The next enzyme in the pathway, lipoyl synthase, catalyzes the conversion of the octanoyl side chain to an active lipoyl, generating a fully active lipoylated domain. The enzyme is an iron-sulfur protein that requires the presence of S-adenosyl-L-methionine. An electron which originates from the [4Fe-4S] cluster of the enzyme serves to split at least two molecules of AdoMet into a 5'-deoxyadenosyl radical and methionine. The radical then abstracts a hydrogen from a C-H bond of the octanoyl side chain, becoming 5'-adenosine in the process. The newly-formed unstable octanoyl radical then reacts directly with the Fe-S center of the enzyme. Two sulfur atoms from the center enter the structure of the octanoyl side chain, producing lipoyl, which dissociates from the enzyme along with excess iron, leaving it with a [2Fe-2S] center. Thus, in this unusual reaction, the iron-sulfur center of the enzyme is not just a catalytic accelerator, but also a substrate, donating the two sulfur atoms. It should be noted that although this process has been well documented in vitro, there is still a possibility that there exists another sulfur donor in vivo, and that the Fe-S center acts as sulfur donor only in the absence of this natural donor. It has been suggested that the conversion of octanoylated-domains to lipoylated ones described in this pathway may be a type of a repair pathway, activated only if the other lipoate biosynthetic pathways are malfunctioning. (EcoCyc) PW002107 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 biotin biosynthesis from 7-keto-8-aminopelargonate PWY0-1507 methylphosphonate degradation PWY0-1533 queuosine biosynthesis PWY-6700 <i>S</i>-adenosyl-L-methionine cycle I PWY-6151 thiazole biosynthesis I (E. coli) PWY-6892 tRNA charging TRNA-CHARGING-PWY lipoate biosynthesis and incorporation II PWY0-1275 formylTHF biosynthesis I 1CMET2-PWY preQ₀ biosynthesis PWY-6703 methionine biosynthesis I HOMOSER-METSYN-PWY 4-amino-2-methyl-5-diphosphomethylpyrimidine biosynthesis PWY-6890 heme biosynthesis from uroporphyrinogen-III II HEMESYN2-PWY superpathway of <i>S</i>-adenosyl-L-methionine biosynthesis SAM-PWY lipoate biosynthesis and incorporation I PWY0-501 Specdb::CMs 615 Specdb::CMs 616 Specdb::CMs 617 Specdb::CMs 1109 Specdb::CMs 1204 Specdb::CMs 2922 Specdb::CMs 30046 Specdb::CMs 30208 Specdb::CMs 30604 Specdb::CMs 30730 Specdb::CMs 30770 Specdb::CMs 31197 Specdb::CMs 31198 Specdb::CMs 37701 Specdb::CMs 170485 Specdb::CMs 1072495 Specdb::CMs 1072497 Specdb::CMs 1072499 Specdb::NmrOneD 1254 Specdb::NmrOneD 1484 Specdb::NmrOneD 4840 Specdb::NmrOneD 20602 Specdb::NmrOneD 20603 Specdb::NmrOneD 20604 Specdb::NmrOneD 20605 Specdb::NmrOneD 20606 Specdb::NmrOneD 20607 Specdb::NmrOneD 20608 Specdb::NmrOneD 20609 Specdb::NmrOneD 20610 Specdb::NmrOneD 20611 Specdb::NmrOneD 20612 Specdb::NmrOneD 20613 Specdb::NmrOneD 20614 Specdb::NmrOneD 20615 Specdb::NmrOneD 20616 Specdb::NmrOneD 20617 Specdb::NmrOneD 20618 Specdb::NmrOneD 20619 Specdb::NmrOneD 20620 Specdb::NmrOneD 20621 Specdb::NmrOneD 166452 Specdb::MsMs 969 Specdb::MsMs 970 Specdb::MsMs 971 Specdb::MsMs 4441 Specdb::MsMs 4442 Specdb::MsMs 4443 Specdb::MsMs 4444 Specdb::MsMs 4445 Specdb::MsMs 4446 Specdb::MsMs 4447 Specdb::MsMs 4448 Specdb::MsMs 4449 Specdb::MsMs 4450 Specdb::MsMs 4451 Specdb::MsMs 4452 Specdb::MsMs 4453 Specdb::MsMs 4454 Specdb::MsMs 4455 Specdb::MsMs 4456 Specdb::MsMs 4457 Specdb::MsMs 4458 Specdb::MsMs 4462 Specdb::MsMs 4463 Specdb::MsMs 179109 Specdb::MsMs 179110 Specdb::NmrTwoD 1031 Specdb::NmrTwoD 1430 HMDB00696 6137 5907 C00073 16811 MET MET_LFZW MET Keseler, I. 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"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 Ishii, N., Nakahigashi, K., Baba, T., Robert, M., Soga, T., Kanai, A., Hirasawa, T., Naba, M., Hirai, K., Hoque, A., Ho, P. Y., Kakazu, Y., Sugawara, K., Igarashi, S., Harada, S., Masuda, T., Sugiyama, N., Togashi, T., Hasegawa, M., Takai, Y., Yugi, K., Arakawa, K., Iwata, N., Toya, Y., Nakayama, Y., Nishioka, T., Shimizu, K., Mori, H., Tomita, M. (2007). "Multiple high-throughput analyses monitor the response of E. coli to perturbations." Science 316:593-597. 17379776 Ball, R. O., Courtney-Martin, G., Pencharz, P. B. (2006). "The in vivo sparing of methionine by cysteine in sulfur amino acid requirements in animal models and adult humans." J Nutr 136:1682S-1693S. 16702340 Sreekumar A, Poisson LM, Rajendiran TM, Khan AP, Cao Q, Yu J, Laxman B, Mehra R, Lonigro RJ, Li Y, Nyati MK, Ahsan A, Kalyana-Sundaram S, Han B, Cao X, Byun J, Omenn GS, Ghosh D, Pennathur S, Alexander DC, Berger A, Shuster JR, Wei JT, Varambally S, Beecher C, Chinnaiyan AM: Metabolomic profiles delineate potential role for sarcosine in prostate cancer progression. Nature. 2009 Feb 12;457(7231):910-4. 19212411 Shoemaker JD, Elliott WH: Automated screening of urine samples for carbohydrates, organic and amino acids after treatment with urease. 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Arch Dis Child. 1974 Jul;49(7):553-9. 4851308 Alton KB, Hernandez A, Alvarez N, Patrick JE: High-performance liquid chromatographic determination of N-[2(S)-(mercaptomethyl)-3-(2-methylphenyl)-1-oxopropyl]-L-methionine, the active plasma metabolite of a prodrug atriopeptidase inhibitor (SCH 42495), using a thiol selective (Au/Hg) amperometric detector. J Chromatogr. 1992 Sep 2;579(2):307-17. 1429978 Fischer JL, Lancia JK, Mathur A, Smith ML: Selenium protection from DNA damage involves a Ref1/p53/Brca1 protein complex. Anticancer Res. 2006 Mar-Apr;26(2A):899-904. 16619485 Ditscheid B, Funfstuck R, Busch M, Schubert R, Gerth J, Jahreis G: Effect of L-methionine supplementation on plasma homocysteine and other free amino acids: a placebo-controlled double-blind cross-over study. Eur J Clin Nutr. 2005 Jun;59(6):768-75. 15870821 Hesse A, Heimbach D: Causes of phosphate stone formation and the importance of metaphylaxis by urinary acidification: a review. World J Urol. 1999 Oct;17(5):308-15. 10552150 Harth G, Horwitz MA: Inhibition of Mycobacterium tuberculosis glutamine synthetase as a novel antibiotic strategy against tuberculosis: demonstration of efficacy in vivo. Infect Immun. 2003 Jan;71(1):456-64. 12496196 Takasu A, Shimosegawa T, Shimosegawa E, Hatazawa J, Kimura K, Fujita M, Koizumi M, Kanno I, Toyota T: 11C-methionine uptake to the pancreas and its secretion: a positron emission tomography study in humans. Pancreas. 1999 May;18(4):392-8. 10231845 van de Poll MC, Dejong CH, Soeters PB: Adequate range for sulfur-containing amino acids and biomarkers for their excess: lessons from enteral and parenteral nutrition. J Nutr. 2006 Jun;136(6 Suppl):1694S-1700S. 16702341 Garlick PJ: Toxicity of methionine in humans. J Nutr. 2006 Jun;136(6 Suppl):1722S-1725S. 16702346 Boy, Matthias; Klein, Daniela; Schroeder, Hartwig. Method for the production and recovery of methionine. PCT Int. Appl. (2005), 34 pp. http://hmdb.ca/system/metabolites/msds/000/000/615/original/HMDB00696.pdf?1358894682 Methionyl-tRNA synthetase P00959 SYM_ECOLI metG http://ecmdb.ca/proteins/P00959.xml Aromatic-amino-acid aminotransferase P04693 TYRB_ECOLI tyrB http://ecmdb.ca/proteins/P04693.xml Peptide methionine sulfoxide reductase msrA P0A744 MSRA_ECOLI msrA http://ecmdb.ca/proteins/P0A744.xml Peptide methionine sulfoxide reductase msrB P0A746 MSRB_ECOLI msrB http://ecmdb.ca/proteins/P0A746.xml S-adenosylmethionine synthase P0A817 METK_ECOLI metK http://ecmdb.ca/proteins/P0A817.xml Pyruvate formate-lyase 1-activating enzyme P0A9N4 PFLA_ECOLI pflA http://ecmdb.ca/proteins/P0A9N4.xml Anaerobic ribonucleoside-triphosphate reductase-activating protein P0A9N8 NRDG_ECOLI nrdG http://ecmdb.ca/proteins/P0A9N8.xml Thioredoxin-2 P0AGG4 THIO2_ECOLI trxC http://ecmdb.ca/proteins/P0AGG4.xml Biotin synthase P12996 BIOB_ECOLI bioB http://ecmdb.ca/proteins/P12996.xml Methionine synthase P13009 METH_ECOLI metH http://ecmdb.ca/proteins/P13009.xml Biotin sulfoxide reductase P20099 BISC_ECOLI bisC http://ecmdb.ca/proteins/P20099.xml 5-methyltetrahydropteroyltriglutamate--homocysteine methyltransferase P25665 METE_ECOLI metE http://ecmdb.ca/proteins/P25665.xml D-methionine transport system permease protein metI P31547 METI_ECOLI metI http://ecmdb.ca/proteins/P31547.xml Lipoate-protein ligase A P32099 LPLA_ECOLI lplA http://ecmdb.ca/proteins/P32099.xml Oxygen-independent coproporphyrinogen-III oxidase P32131 HEMN_ECOLI hemN http://ecmdb.ca/proteins/P32131.xml Pyruvate formate-lyase 2-activating enzyme P32675 PFLC_ECOLI pflC http://ecmdb.ca/proteins/P32675.xml Oxygen-independent coproporphyrinogen-III oxidase-like protein yggW P52062 YGGW_ECOLI yggW http://ecmdb.ca/proteins/P52062.xml Lipoyl synthase P60716 LIPA_ECOLI lipA http://ecmdb.ca/proteins/P60716.xml Putative pyruvate formate-lyase 3-activating enzyme P75794 PFLE_ECOLI ybiY http://ecmdb.ca/proteins/P75794.xml Homocysteine S-methyltransferase Q47690 MMUM_ECOLI mmuM http://ecmdb.ca/proteins/Q47690.xml Methionine import ATP-binding protein MetN P30750 METN_ECOLI metN http://ecmdb.ca/proteins/P30750.xml Thiazole synthase P30139 THIG_ECOLI thiG http://ecmdb.ca/proteins/P30139.xml Dehydroglycine synthase P30140 THIH_ECOLI thiH http://ecmdb.ca/proteins/P30140.xml D-methionine-binding lipoprotein metQ P28635 METQ_ECOLI metQ http://ecmdb.ca/proteins/P28635.xml Phosphomethylpyrimidine synthase P30136 THIC_ECOLI thiC http://ecmdb.ca/proteins/P30136.xml Thioredoxin-1 P0AA25 THIO_ECOLI trxA http://ecmdb.ca/proteins/P0AA25.xml predicted acyltransferase with acyl-CoA N-acyltransferase domain P76112 yncA http://ecmdb.ca/proteins/P76112.xml S-adenosylmethionine:tRNA ribosyltransferase-isomerase P0A7F9 QUEA_ECOLI queA http://ecmdb.ca/proteins/P0A7F9.xml Ribosomal RNA large subunit methyltransferase N P36979 RLMN_ECOLI rlmN http://ecmdb.ca/proteins/P36979.xml tRNA-2-methylthio-N(6)-dimethylallyladenosine synthase P0AEI1 MIAB_ECOLI miaB http://ecmdb.ca/proteins/P0AEI1.xml Ribosomal protein S12 methylthiotransferase RimO P0AEI4 RIMO_ECOLI rimO http://ecmdb.ca/proteins/P0AEI4.xml D-methionine transport system permease protein metI P31547 METI_ECOLI metI http://ecmdb.ca/proteins/P31547.xml Uncharacterized amino-acid ABC transporter ATP-binding protein yecC P37774 YECC_ECOLI yecC http://ecmdb.ca/proteins/P37774.xml Inner membrane amino-acid ABC transporter permease protein yecS P0AFT2 YECS_ECOLI yecS http://ecmdb.ca/proteins/P0AFT2.xml Methionine import ATP-binding protein MetN P30750 METN_ECOLI metN http://ecmdb.ca/proteins/P30750.xml Outer membrane protein N P77747 OMPN_ECOLI ompN http://ecmdb.ca/proteins/P77747.xml Outer membrane pore protein E P02932 PHOE_ECOLI phoE http://ecmdb.ca/proteins/P02932.xml Outer membrane protein F P02931 OMPF_ECOLI ompF http://ecmdb.ca/proteins/P02931.xml D-methionine-binding lipoprotein metQ P28635 METQ_ECOLI metQ http://ecmdb.ca/proteins/P28635.xml Outer membrane protein C P06996 OMPC_ECOLI ompC http://ecmdb.ca/proteins/P06996.xml Methionine sulfoxide + Reduced Thioredoxin > Water + L-Methionine + Oxidized Thioredoxin Adenosine triphosphate + Water + L-Methionine > ADP + Hydrogen ion + L-Methionine + Phosphate RXN0-4522 Adenosine triphosphate + Water + L-Methionine > ADP + Hydrogen ion + L-Methionine + Phosphate RXN0-4522 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 [4Fe-4S] iron-sulfur cluster + 2 S-Adenosylmethionine + Hydrogen ion + NAD + octanoate (protein bound) > [2Fe-2S] iron-sulfur cluster +2 5'-Deoxyadenosine +2 Iron + lipoate (protein bound) +2 L-Methionine + NADH [2Fe-2S] iron-sulfur cluster + S-Adenosylmethionine + Dethiobiotin > [2Fe-1S] desulfurated iron-sulfur cluster + Biotin + 5'-Deoxyadenosine + Hydrogen ion + L-Methionine Adenosine triphosphate + L-Methionine + tRNA(Met) > Adenosine monophosphate + L-Methionyl-tRNA (Met) + Pyrophosphate Adenosine triphosphate + Water + L-Methionine <> S-Adenosylmethionine + Phosphate + Pyrophosphate R00177 S-ADENMETSYN-RXN 2 S-Adenosylmethionine + Coproporphyrin III <>2 Carbon dioxide +2 5'-Deoxyadenosine +2 L-Methionine + Protoporphyrinogen IX R06895 S-Adenosylmethionine + NADPH + L-Tyrosine > p-Cresol + 5'-Deoxyadenosine + Dehydroglycine + Hydrogen ion + L-Methionine + NADP Hydrogen peroxide + L-Methionine > Water + Methionine sulfoxide Phosphate + Pyrophosphate + S-Adenosylmethionine <> Adenosine triphosphate + L-Methionine + Water R00177 S-Adenosylmethionine + L-Homocysteine <> S-Adenosylhomocysteine + L-Methionine R00650 HOMOCYSTEINE-S-METHYLTRANSFERASE-RXN 5-Methyltetrahydrofolic acid + L-Homocysteine <> Tetrahydrofolic acid + L-Methionine R00946 Dethiobiotin + Sulfur donor + 2 S-Adenosylmethionine + 2 e- + 2 Hydrogen ion <> Biotin +2 L-Methionine +2 5'-Deoxyadenosine R01078 Adenosine triphosphate + L-Methionine + tRNA(Met) + tRNA(Met) <> Adenosine monophosphate + Pyrophosphate + L-Methionyl-tRNA + L-Methionyl-tRNA R03659 5-Methyltetrahydropteroyltri-L-glutamic acid + L-Homocysteine <> Tetrahydropteroyltri-L-glutamic acid + L-Methionine R04405 2-Oxo-4-methylthiobutanoic acid + L-Glutamate <> L-Methionine + alpha-Ketoglutarate R07396 Protein N6-(octanoyl)lysine + 2 Sulfur donor + 2 S-Adenosylmethionine + Protein N6-(octanoyl)lysine <> Protein N6-(lipoyl)lysine +2 L-Methionine +2 5'-Deoxyadenosine + Protein N6-(lipoyl)lysine R07767 Octanoyl-[acp] + 2 Sulfur donor + 2 S-Adenosylmethionine <> Lipoyl-[acp] +2 L-Methionine +2 5'-Deoxyadenosine R07768 L-Methionine + Hydrogen peroxide > L-methionine <i>S</i>-oxide + Water RXN0-6721 Hydrogen ion + &alpha;-D-ribose-1-methylphosphonate-5-phosphate + S-Adenosylmethionine > &alpha;-D-ribose-1,2-cyclic-phosphate-5-phosphate + methane + 5'-Deoxyadenosine + L-Methionine RXN0-6734 L-Methionine + Acetyl-CoA N-&alpha;-acetyl-L-methionine + Coenzyme A RXN0-6948 <i>S</i>-sulfanyl-[acceptor] + Dethiobiotin + S-Adenosylmethionine > an unsulfurated sulfur acceptor + Biotin + 5'-Deoxyadenosine + L-Methionine + Hydrogen ion 2.8.1.6-RXN a protein with N-terminal methionine + Water > L-Methionine + Peptides 3.4.11.18-RXN Coproporphyrinogen III + S-Adenosylmethionine > Protoporphyrinogen IX + Carbon dioxide + L-Methionine + 5'-Deoxyadenosine HEMN-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 5-Aminoimidazole ribonucleotide + S-Adenosylmethionine 4-Amino-2-methyl-5-phosphomethylpyrimidine + 5'-Deoxyadenosine + L-Methionine + Formic acid + carbon monoxide + Hydrogen ion PYRIMSYN1-RXN L-Methionine + a 2-oxo carboxylate 2-Oxo-4-methylthiobutanoic acid + a standard &alpha; amino acid R15-RXN S-Adenosylmethionine + Ribonuc-tri-P-reductases-inactive <> 5'-Deoxyadenosine + L-Methionine + Ribonuc-tri-P-reductases-active RNTRACTIV-RXN L-Tyrosine + S-Adenosylmethionine + a reduced electron acceptor > Dehydroglycine + p-Cresol + 5'-Deoxyadenosine + L-Methionine + an oxidized electron acceptor + Hydrogen ion RXN-11319 Water + Adenosine triphosphate + L-Methionine > Phosphate + ADP + L-Methionine + Hydrogen ion RXN0-4522 Water + Adenosine triphosphate + L-Methionine > Phosphate + ADP + L-Methionine + Hydrogen ion RXN0-4522 N-6-isopentyl adenosine-37 tRNA + S-Adenosylmethionine + <i>S</i>-sulfanyl-[acceptor] 2-methylthio-N-6-isopentyl adenosine-37 tRNA + S-Adenosylhomocysteine + L-Methionine + 5'-Deoxyadenosine + an unsulfurated sulfur acceptor + Hydrogen ion RXN0-5063 6-Carboxy-5,6,7,8-tetrahydropterin + S-Adenosylmethionine + Hydrogen ion > 7-carboxy-7-deazaguanine + 5'-Deoxyadenosine + L-Methionine + Ammonia RXN0-6575 gly-met + Water > Glycine + L-Methionine RXN0-6974 methionine-alanine dipeptide + Water > L-Methionine + L-Alanine RXN0-6985 Adenosine triphosphate + L-Methionine + Water > Phosphate + Pyrophosphate + S-Adenosylmethionine S-ADENMETSYN-RXN Dethiobiotin + Hydrogen sulfide + 2 S-adenosyl-L-methionine > Biotin +2 L-Methionine +2 5'-Deoxyadenosine Coproporphyrinogen III + 2 S-adenosyl-L-methionine > Protoporphyrinogen IX +2 Carbon dioxide +2 L-Methionine +2 5'-Deoxyadenosine Protein N(6)-(octanoyl)lysine + 2 Hydrogen sulfide + 2 S-adenosyl-L-methionine > protein N(6)-(lipoyl)lysine +2 L-Methionine +2 5'-Deoxyadenosine 5-methyltetrahydropteroyltri-L-glutamate + L-Homocysteine > tetrahydropteroyltri-L-glutamate + L-Methionine 5-Methyltetrahydrofolic acid + L-Homocysteine > Tetrahydrofolic acid + L-Methionine Adenosine triphosphate + L-Methionine + Water > Inorganic phosphate + Pyrophosphate + S-adenosyl-L-methionine S-methyl-L-methionine + L-Homocysteine >2 L-Methionine L-Methionine + thioredoxin disulfide + Water > L-methionine (S)-S-oxide + thioredoxin L-Methionine + thioredoxin disulfide + Water > L-Methionine (R)-S-oxide + thioredoxin S-adenosyl-L-methionine + dihydroflavodoxin + [formate C-acetyltransferase]-glycine > 5'-Deoxyadenosine + L-Methionine + flavodoxin semiquinone + [formate C-acetyltransferase]-glycin-2-yl radical S-adenosyl-L-methionine + 7-Aminomethyl-7-deazaguanosine > L-Methionine + Adenine + epoxyqueuosine 2 S-adenosyl-L-methionine + adenine(2503) in 23S rRNA > S-Adenosylhomocysteine + L-Methionine + 5'-Deoxyadenosine + 2-methyladenine(2503) in 23S rRNA Adenosine triphosphate + L-Methionine + tRNA(Met) > Adenosine monophosphate + Pyrophosphate + L-methionyl-tRNA(Met) 5-Aminoimidazole ribonucleotide + S-adenosyl-L-methionine > 4-Amino-2-methyl-5-phosphomethylpyrimidine + 5'-Deoxyadenosine + L-Methionine + Formic acid + CO L-Tyrosine + S-adenosyl-L-methionine + reduced acceptor > 2-iminoacetate + p-Cresol + 5'-Deoxyadenosine + L-Methionine + acceptor +2 Hydrogen ion L-Methionine + a 2-oxo acid > 2-Oxo-4-methylthiobutanoic acid + an L-amino acid Acetyl-CoA + L-Methionine > CoA + N-Acetyl-L-methionine 2 S-Adenosylmethionine <> S-Adenosylhomocysteine +2 L-Methionine + 5'-Deoxyadenosine R10645 2 S-Adenosylmethionine + Reduced acceptor <> S-Adenosylhomocysteine +2 L-Methionine + 5'-Deoxyadenosine R10652 L-Tyrosine + S-Adenosylmethionine + NADPH <> 2-iminoacetate + p-Cresol + 5'-Deoxyadenosine + L-Methionine + NADP + Hydrogen ion R10246 4-Amino-5-hydroxymethyl-2-methylpyrimidine + S-Adenosylmethionine <> 5-Aminoimidazole ribonucleotide + 4-Amino-2-methyl-5-phosphomethylpyrimidine + 5'-Deoxyadenosine + L-Methionine + Formic acid + CO R03472 Peptide-L-methionine + Thioredoxin disulfide + Water + L-Methionine <> Peptide-L-methionine (S)-S-oxide + Thioredoxin + L-methionine (S)-S-oxide R04120 Dethiobiotin + 2 S-adenosyl-L-methionine + 2 Hydrogen ion + a sulfurated [sulfur carrier] > Biotin +2 L-Methionine +2 5'-Deoxyadenosine PW_R002499 Octanoyl-[acyl-carrier protein] + 2 a sulfur donor + 2 S-adenosyl-L-methionine > Lipoyl-ACP +2 L-Methionine + 5'-Deoxyadenosine PW_R002519 Protein N6-(octanoyl)lysine + 2 a sulfur donor + 2 S-adenosyl-L-methionine > Protein N6-(lipoyl)lysine +2 L-Methionine +2 5'-Deoxyadenosine PW_R002522 Protein N6-(octanoyl)lysine + 2 Reduced ferredoxin + 2 a sulfurated [sulfur carrier]  + 2 S-adenosyl-L-methionine >2 L-Methionine +2 5'-Deoxyadenosine + Oxidized ferredoxin + Protein N6-(lipoyl)lysine + an unsulfurated [sulfur carrier] PW_R003564 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-Methionine + Adenosine triphosphate + Hydrogen ion + tRNA(Met) > Adenosine monophosphate + Pyrophosphate + L-methionyl-tRNA(Met) PW_R002841 Homocysteine + N5-methyl--tetrahydropteroyl tri-L-glutamate + Homocysteine > tetrahydropteroyltri-L-glutamate + L-Methionine PW_R002892 L-Methionine + Water + Adenosine triphosphate > Phosphate + Pyrophosphate PW_R003074 L-Methionine + Water + Adenosine triphosphate > Phosphate + Pyrophosphate + S-adenosyl-L-methionine PW_R003075 S-adenosyl-L-methionine + Coproporphyrinogen III > 5'-Deoxyadenosine + L-Methionine + Carbon dioxide + Protoporphyrinogen IX PW_R003483 L-Tyrosine + NADPH + S-adenosyl-L-methionine + L-Tyrosine + NADPH > Hydrogen ion + NADP + L-Methionine + 5'-Deoxyadenosine + p-Cresol + 2-iminoacetate PW_R005174 7-aminomethyl-7-deazaguanosine34 in tRNA + S-adenosyl-L-methionine > Hydrogen ion + L-Methionine + Adenine + epoxyqueuosine PW_R005185 L-Methionine + Adenosine triphosphate + Water > Adenosine diphosphate + Phosphate + Hydrogen ion + L-Methionine + ADP PW_RCT000111 L-Methionine + Adenosine triphosphate + Water > Adenosine diphosphate + Phosphate + Hydrogen ion + L-Methionine + ADP PW_RCT000111 L-Methionine + Adenosine triphosphate + Water > Adenosine diphosphate + Pyrophosphate + Hydrogen ion + L-Methionine + ADP PW_RCT000125 L-Methionine + Adenosine triphosphate + Water > Adenosine diphosphate + Pyrophosphate + Hydrogen ion + L-Methionine + ADP PW_RCT000125 Homocysteine + S-Methylmethionine <>2 L-Methionine + Hydrogen ion PW_R005874 5-Aminoimidazole ribonucleotide + S-adenosyl-L-methionine >3 Hydrogen ion + CO + Formic acid + L-Methionine + 5'-Deoxyadenosine + 4-amino-2-methyl-5-phosphomethylpyrimidine PW_R005931 L-Tyrosine + S-adenosyl-L-methionine + NADPH > Dehydroglycine + 4-Methylcatechol + 5'-Deoxyadenosine + L-Methionine + NADP + Hydrogen ion PW_R005962 a [lipoyl-carrier protein] N6-octanoyl-L-lysine + 2 S-adenosyl-L-methionine + 2 a sulfurated [sulfur carrier]  + 2 Reduced ferredoxin > Protein N6-(lipoyl)lysine +2 5'-Deoxyadenosine +2 L-Methionine +2 an unsulfurated [sulfur carrier] +2 Oxidized ferredoxin PW_R006138 2 S-Adenosylmethionine + Coproporphyrin III <>2 Carbon dioxide +2 5'-Deoxyadenosine +2 L-Methionine + Protoporphyrinogen IX Dethiobiotin + Sulfur donor + 2 S-Adenosylmethionine + 2 e- + 2 Hydrogen ion <> Biotin +2 L-Methionine +2 5'-Deoxyadenosine Adenosine triphosphate + Water + L-Methionine <> S-Adenosylmethionine + Phosphate + Pyrophosphate 2 S-Adenosylmethionine + Reduced acceptor <> S-Adenosylhomocysteine +2 L-Methionine +5 5'-Deoxyadenosine 5 5-Methyltetrahydrofolic acid + L-Homocysteine <> Hydrogen ion + L-Methionine + Tetrahydrofolic acid Adenosine triphosphate + L-Methionine + tRNA(Met) <> Adenosine monophosphate + Pyrophosphate + L-Methionyl-tRNA 2 S-Adenosylmethionine <> S-Adenosylhomocysteine +2 L-Methionine +5 5'-Deoxyadenosine 4 4-Amino-5-hydroxymethyl-2-methylpyrimidine + S-Adenosylmethionine <>5 5-Aminoimidazole ribonucleotide +4 4-Amino-2-methyl-5-phosphomethylpyrimidine +5 5'-Deoxyadenosine + L-Methionine + Formic acid + CO Peptide-L-methionine + Thioredoxin disulfide + Water + L-Methionine <> Peptide-L-methionine (S)-S-oxide + Thioredoxin + L-methionine (S)-S-oxide 2 S-Adenosylmethionine + Coproporphyrin III <>2 Carbon dioxide +2 5'-Deoxyadenosine +2 L-Methionine + Protoporphyrinogen IX Dethiobiotin + Sulfur donor + 2 S-Adenosylmethionine + 2 e- + 2 Hydrogen ion <> Biotin +2 L-Methionine +2 5'-Deoxyadenosine 2 S-Adenosylmethionine + Reduced acceptor <> S-Adenosylhomocysteine +2 L-Methionine +5 5'-Deoxyadenosine 2 S-Adenosylmethionine + Coproporphyrin III <>2 Carbon dioxide +2 5'-Deoxyadenosine +2 L-Methionine + Protoporphyrinogen IX 5 5-Methyltetrahydrofolic acid + L-Homocysteine <> Hydrogen ion + L-Methionine + Tetrahydrofolic acid Protein N6-(octanoyl)lysine + 2 Sulfur donor + 2 S-Adenosylmethionine <> Protein N6-(lipoyl)lysine +2 L-Methionine +2 5'-Deoxyadenosine Adenosine triphosphate + L-Methionine + tRNA(Met) <> Adenosine monophosphate + Pyrophosphate + L-Methionyl-tRNA 4 4-Amino-5-hydroxymethyl-2-methylpyrimidine + S-Adenosylmethionine <>5 5-Aminoimidazole ribonucleotide +4 4-Amino-2-methyl-5-phosphomethylpyrimidine +5 5'-Deoxyadenosine + L-Methionine + Formic acid + CO Peptide-L-methionine + Thioredoxin disulfide + Water + L-Methionine <> Peptide-L-methionine (S)-S-oxide + Thioredoxin + L-methionine (S)-S-oxide 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 145.0 uM 0.0 37 oC K12 NCM3722 Mid-Log Phase 580000 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 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 glycerol Shake flask and filter culture 129.0 uM 0.0 37 oC K12 NCM3722 Mid-Log Phase 516000 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 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 acetate Shake flask and filter culture 65.9 uM 0.0 37 oC K12 NCM3722 Mid-Log Phase 263600 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 48 mM Na2HPO4, 22 mM KH2PO4, 10 mM NaCl, 45 mM (NH4)2SO4, supplemented with 1 mM MgSO4, 1 mg/l thiamine·HCl, 5.6 mg/l CaCl2, 8 mg/l FeCl3, 1 mg/l MnCl2·4H2O, 1.7 mg/l ZnCl2, 0.43 mg/l CuCl2·2H2O, 0.6 mg/l CoCl2·2H2O and 0.6 mg/l Na2MoO4·2H2O. 4 g/L Gluco Bioreactor, pH controlled, O2 and CO2 controlled, dilution rate: 0.2/h 30.3 uM 0.0 37 oC BW25113 Stationary Phase, glucose limited 121200 0 Ishii, N., Nakahigashi, K., Baba, T., Robert, M., Soga, T., Kanai, A., Hirasawa, T., Naba, M., Hirai, K., Hoque, A., Ho, P. Y., Kakazu, Y., Sugawara, K., Igarashi, S., Harada, S., Masuda, T., Sugiyama, N., Togashi, T., Hasegawa, M., Takai, Y., Yugi, K., Arakawa, K., Iwata, N., Toya, Y., Nakayama, Y., Nishioka, T., Shimizu, K., Mori, H., Tomita, M. (2007). "Multiple high-throughput analyses monitor the response of E. coli to perturbations." Science 316:593-597. 17379776 Luria-Bertani (LB) media Shake flask 58.4 uM true 7.0 37 oC BL21 DE3 Stationary phase cultures (overnight culture) 233600 28000 Lin, Z., Johnson, L. C., Weissbach, H., Brot, N., Lively, M. O., Lowther, W. T. (2007). "Free methionine-(R)-sulfoxide reductase from Escherichia coli reveals a new GAF domain function." Proc Natl Acad Sci U S A 104:9597-9602. 17535911 Luria-Bertani (LB) media Shake flask 42.57 uM true 4.75 37 oC BL21 DE3 Stationary phase cultures (overnight culture) 170267 19000 Lin, Z., Johnson, L. C., Weissbach, H., Brot, N., Lively, M. O., Lowther, W. T. (2007). "Free methionine-(R)-sulfoxide reductase from Escherichia coli reveals a new GAF domain function." Proc Natl Acad Sci U S A 104:9597-9602. 17535911