2.0 2012-05-31 09:57:21 -0600 2015-09-13 12:56:06 -0600 ECMDB00099 M2MDB000038 L-Cystathionine Cystathionine is an intermediate in the synthesis of cysteine. It is generated from homocysteine and serine by cystathionine beta synthase. It is cleaved into cysteine and ketobutyrate by cystathionine gamma-lyase. (Wikipedia) (R)-S-(2-amino-2-carboxyethyl)-L-Homocysteine Cystathionine L-(+)-Cystathionine S-[(2R)-2-Amino-2-carboxyethyl]-L-Homocysteine [R-(R*,S*)]-2-amino-4-[(2-amino-2-carboxyethyl)thio]-Butanoate [R-(R*,S*)]-2-amino-4-[(2-amino-2-carboxyethyl)thio]-Butanoic acid C7H14N2O4S 222.262 222.067427636 (2S)-2-amino-4-{[(2R)-2-amino-2-carboxyethyl]sulfanyl}butanoic acid L-cystathionine 56-88-2 N[C@@H](CCSC[C@H](N)C(O)=O)C(O)=O InChI=1S/C7H14N2O4S/c8-4(6(10)11)1-2-14-3-5(9)7(12)13/h4-5H,1-3,8-9H2,(H,10,11)(H,12,13)/t4-,5-/m0/s1 ILRYLPWNYFXEMH-WHFBIAKZSA-N Solid Cytosol logp -4.01 ALOGPS logs -1.11 ALOGPS solubility 1.73e+01 g/l ALOGPS melting_point 312 oC logp -5.8 ChemAxon pka_strongest_acidic 1.79 ChemAxon pka_strongest_basic 9.66 ChemAxon iupac (2S)-2-amino-4-{[(2R)-2-amino-2-carboxyethyl]sulfanyl}butanoic acid ChemAxon average_mass 222.262 ChemAxon mono_mass 222.067427636 ChemAxon smiles N[C@@H](CCSC[C@H](N)C(O)=O)C(O)=O ChemAxon formula C7H14N2O4S ChemAxon inchi InChI=1S/C7H14N2O4S/c8-4(6(10)11)1-2-14-3-5(9)7(12)13/h4-5H,1-3,8-9H2,(H,10,11)(H,12,13)/t4-,5-/m0/s1 ChemAxon inchikey ILRYLPWNYFXEMH-WHFBIAKZSA-N ChemAxon polar_surface_area 126.64 ChemAxon refractivity 51.57 ChemAxon polarizability 22.02 ChemAxon rotatable_bond_count 7 ChemAxon acceptor_count 6 ChemAxon donor_count 4 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 Glycine, serine and threonine metabolism ec00260 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 Metabolic pathways eco01100 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 methionine biosynthesis I HOMOSER-METSYN-PWY Specdb::CMs 322 Specdb::CMs 1814 Specdb::CMs 1842 Specdb::CMs 1869 Specdb::CMs 2709 Specdb::CMs 30761 Specdb::CMs 30995 Specdb::CMs 30996 Specdb::CMs 30997 Specdb::CMs 37294 Specdb::CMs 173698 Specdb::CMs 1050007 Specdb::CMs 1050008 Specdb::CMs 1050010 Specdb::CMs 1050012 Specdb::CMs 1050013 Specdb::CMs 1050015 Specdb::CMs 1050017 Specdb::CMs 1050019 Specdb::CMs 1050021 Specdb::CMs 1050023 Specdb::CMs 1050024 Specdb::CMs 1050026 Specdb::CMs 1050028 Specdb::CMs 1050030 Specdb::NmrOneD 1084 Specdb::NmrOneD 4806 Specdb::NmrOneD 4807 Specdb::NmrOneD 142190 Specdb::NmrOneD 142191 Specdb::NmrOneD 142192 Specdb::NmrOneD 142193 Specdb::NmrOneD 142194 Specdb::NmrOneD 142195 Specdb::NmrOneD 142196 Specdb::NmrOneD 142197 Specdb::NmrOneD 142198 Specdb::NmrOneD 142199 Specdb::NmrOneD 142200 Specdb::NmrOneD 142201 Specdb::NmrOneD 142202 Specdb::NmrOneD 142203 Specdb::NmrOneD 142204 Specdb::NmrOneD 142205 Specdb::NmrOneD 142206 Specdb::NmrOneD 142207 Specdb::NmrOneD 142208 Specdb::NmrOneD 142209 Specdb::MsMs 156 Specdb::MsMs 157 Specdb::MsMs 158 Specdb::MsMs 2862 Specdb::MsMs 2863 Specdb::MsMs 2864 Specdb::MsMs 2865 Specdb::MsMs 2866 Specdb::MsMs 2867 Specdb::MsMs 2868 Specdb::MsMs 2870 Specdb::MsMs 2871 Specdb::MsMs 2872 Specdb::MsMs 178707 Specdb::MsMs 178708 Specdb::MsMs 178709 Specdb::MsMs 181026 Specdb::MsMs 181027 Specdb::MsMs 181028 Specdb::MsMs 439052 Specdb::MsMs 445895 Specdb::MsMs 445896 Specdb::MsMs 445897 Specdb::MsMs 445898 Specdb::MsMs 445899 Specdb::NmrTwoD 1142 HMDB00099 439258 388392 C02291 17482 L-CYSTATHIONINE Cystathionine Keseler, I. 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Applied and Environmental Microbiology (2004), 70(6), 3766-3768. http://hmdb.ca/system/metabolites/msds/000/000/069/original/HMDB00099.pdf?1358462918 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 Protein malY P23256 MALY_ECOLI malY http://ecmdb.ca/proteins/P23256.xml Dipeptide transport system permease protein dppB P0AEF8 DPPB_ECOLI dppB http://ecmdb.ca/proteins/P0AEF8.xml Dipeptide transport system permease protein dppC P0AEG1 DPPC_ECOLI dppC http://ecmdb.ca/proteins/P0AEG1.xml Oligopeptide transport system permease protein oppB P0AFH2 OPPB_ECOLI oppB http://ecmdb.ca/proteins/P0AFH2.xml Oligopeptide transport system permease protein oppC P0AFH6 OPPC_ECOLI oppC http://ecmdb.ca/proteins/P0AFH6.xml Dipeptide transport system permease protein dppB P0AEF8 DPPB_ECOLI dppB http://ecmdb.ca/proteins/P0AEF8.xml Dipeptide transport system permease protein dppC P0AEG1 DPPC_ECOLI dppC http://ecmdb.ca/proteins/P0AEG1.xml Oligopeptide transport system permease protein oppB P0AFH2 OPPB_ECOLI oppB http://ecmdb.ca/proteins/P0AFH2.xml Oligopeptide transport system permease protein oppC P0AFH6 OPPC_ECOLI oppC http://ecmdb.ca/proteins/P0AFH6.xml Peptide transport system permease protein sapB P0AGH3 SAPB_ECOLI sapB http://ecmdb.ca/proteins/P0AGH3.xml Peptide transport system permease protein sapC P0AGH5 SAPC_ECOLI sapC http://ecmdb.ca/proteins/P0AGH5.xml Dipeptide and tripeptide permease B P36837 DTPB_ECOLI dtpB http://ecmdb.ca/proteins/P36837.xml Probable dipeptide and tripeptide permease YjdL P39276 YJDL_ECOLI yjdL http://ecmdb.ca/proteins/P39276.xml Dipeptide permease D P75742 DTPD_ECOLI dtpD http://ecmdb.ca/proteins/P75742.xml Dipeptide and tripeptide permease A P77304 DTPA_ECOLI dtpA http://ecmdb.ca/proteins/P77304.xml L-Cystathionine + Water > L-Homocysteine + Ammonium + Pyruvic acid L-Cysteine + O-Succinyl-L-homoserine <> L-Cystathionine + Hydrogen ion + Succinic acid R03260 O-SUCCHOMOSERLYASE-RXN L-Cystathionine + Water <> L-Homocysteine + Ammonia + Pyruvic acid R01286 o-acetyl-l-homoserine + L-Cysteine <> L-Cystathionine + Acetic acid R03217 O-Succinyl-L-homoserine + L-Cysteine <> L-Cystathionine + Succinic acid R03260 L-Cystathionine + Water > Hydrogen ion + Pyruvic acid + Ammonia + L-Homocysteine R01286 CYSTATHIONINE-BETA-LYASE-RXN L-Cysteine + O-Succinyl-L-homoserine > Hydrogen ion + Succinic acid + L-Cystathionine O-SUCCHOMOSERLYASE-RXN L-Cystathionine + Water > L-Homocysteine + Ammonia + Pyruvic acid O-Succinyl-L-homoserine + L-Cysteine > L-Cystathionine + Succinic acid L-Cystathionine + Water + 2-Aminoacrylic acid + 2-Iminopropanoate <> L-Homocysteine + Pyruvic acid + Ammonia R01286 L-Cystathionine > Hydrogen ion + Homocysteine + 2-aminoprop-2-enoate + Homocysteine PW_R002891