2.02012-05-31 09:57:21 -06002015-09-13 12:56:06 -0600ECMDB00099M2MDB000038L-CystathionineCystathionine 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-HomocysteineCystathionineL-(+)-CystathionineS-[(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 acidC7H14N2O4S222.262222.067427636(2S)-2-amino-4-{[(2R)-2-amino-2-carboxyethyl]sulfanyl}butanoic acidL-cystathionine56-88-2N[C@@H](CCSC[C@H](N)C(O)=O)C(O)=OInChI=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/s1ILRYLPWNYFXEMH-WHFBIAKZSA-NSolidCytosollogp-4.01logs-1.11solubility1.73e+01 g/lmelting_point312 oClogp-5.8pka_strongest_acidic1.79pka_strongest_basic9.66iupac(2S)-2-amino-4-{[(2R)-2-amino-2-carboxyethyl]sulfanyl}butanoic acidaverage_mass222.262mono_mass222.067427636smilesN[C@@H](CCSC[C@H](N)C(O)=O)C(O)=OformulaC7H14N2O4SinchiInChI=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/s1inchikeyILRYLPWNYFXEMH-WHFBIAKZSA-Npolar_surface_area126.64refractivity51.57polarizability22.02rotatable_bond_count7acceptor_count6donor_count4physiological_charge0formal_charge0Nitrogen 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.
PW000755ec00910MetabolicCysteine and methionine metabolismec00270Glycine, serine and threonine metabolismec00260Selenoamino acid metabolismec00450Sulfur metabolismThe 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.PW000922ec00920MetabolicMetabolic pathwayseco01100methionine biosynthesisThe 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.PW000814Metabolicmethionine biosynthesis IHOMOSER-METSYN-PWYSpecdb::CMs322Specdb::CMs1814Specdb::CMs1842Specdb::CMs1869Specdb::CMs2709Specdb::CMs30761Specdb::CMs30995Specdb::CMs30996Specdb::CMs30997Specdb::CMs37294Specdb::CMs173698Specdb::CMs1050007Specdb::CMs1050008Specdb::CMs1050010Specdb::CMs1050012Specdb::CMs1050013Specdb::CMs1050015Specdb::CMs1050017Specdb::CMs1050019Specdb::CMs1050021Specdb::CMs1050023Specdb::CMs1050024Specdb::CMs1050026Specdb::CMs1050028Specdb::CMs1050030Specdb::NmrOneD1084Specdb::NmrOneD4806Specdb::NmrOneD4807Specdb::NmrOneD142190Specdb::NmrOneD142191Specdb::NmrOneD142192Specdb::NmrOneD142193Specdb::NmrOneD142194Specdb::NmrOneD142195Specdb::NmrOneD142196Specdb::NmrOneD142197Specdb::NmrOneD142198Specdb::NmrOneD142199Specdb::NmrOneD142200Specdb::NmrOneD142201Specdb::NmrOneD142202Specdb::NmrOneD142203Specdb::NmrOneD142204Specdb::NmrOneD142205Specdb::NmrOneD142206Specdb::NmrOneD142207Specdb::NmrOneD142208Specdb::NmrOneD142209Specdb::MsMs156Specdb::MsMs157Specdb::MsMs158Specdb::MsMs2862Specdb::MsMs2863Specdb::MsMs2864Specdb::MsMs2865Specdb::MsMs2866Specdb::MsMs2867Specdb::MsMs2868Specdb::MsMs2870Specdb::MsMs2871Specdb::MsMs2872Specdb::MsMs178707Specdb::MsMs178708Specdb::MsMs178709Specdb::MsMs181026Specdb::MsMs181027Specdb::MsMs181028Specdb::MsMs439052Specdb::MsMs445895Specdb::MsMs445896Specdb::MsMs445897Specdb::MsMs445898Specdb::MsMs445899Specdb::NmrTwoD1142HMDB00099439258388392C0229117482L-CYSTATHIONINECystathionineKeseler, 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?1358462918Cystathionine gamma-synthaseP00935METB_ECOLImetBhttp://ecmdb.ca/proteins/P00935.xmlCystathionine beta-lyase metCP06721METC_ECOLImetChttp://ecmdb.ca/proteins/P06721.xmlProtein malYP23256MALY_ECOLImalYhttp://ecmdb.ca/proteins/P23256.xmlDipeptide transport system permease protein dppBP0AEF8DPPB_ECOLIdppBhttp://ecmdb.ca/proteins/P0AEF8.xmlDipeptide transport system permease protein dppCP0AEG1DPPC_ECOLIdppChttp://ecmdb.ca/proteins/P0AEG1.xmlOligopeptide transport system permease protein oppBP0AFH2OPPB_ECOLIoppBhttp://ecmdb.ca/proteins/P0AFH2.xmlOligopeptide transport system permease protein oppCP0AFH6OPPC_ECOLIoppChttp://ecmdb.ca/proteins/P0AFH6.xmlDipeptide transport system permease protein dppBP0AEF8DPPB_ECOLIdppBhttp://ecmdb.ca/proteins/P0AEF8.xmlDipeptide transport system permease protein dppCP0AEG1DPPC_ECOLIdppChttp://ecmdb.ca/proteins/P0AEG1.xmlOligopeptide transport system permease protein oppBP0AFH2OPPB_ECOLIoppBhttp://ecmdb.ca/proteins/P0AFH2.xmlOligopeptide transport system permease protein oppCP0AFH6OPPC_ECOLIoppChttp://ecmdb.ca/proteins/P0AFH6.xmlPeptide transport system permease protein sapBP0AGH3SAPB_ECOLIsapBhttp://ecmdb.ca/proteins/P0AGH3.xmlPeptide transport system permease protein sapCP0AGH5SAPC_ECOLIsapChttp://ecmdb.ca/proteins/P0AGH5.xmlDipeptide and tripeptide permease BP36837DTPB_ECOLIdtpBhttp://ecmdb.ca/proteins/P36837.xmlProbable dipeptide and tripeptide permease YjdLP39276YJDL_ECOLIyjdLhttp://ecmdb.ca/proteins/P39276.xmlDipeptide permease DP75742DTPD_ECOLIdtpDhttp://ecmdb.ca/proteins/P75742.xmlDipeptide and tripeptide permease AP77304DTPA_ECOLIdtpAhttp://ecmdb.ca/proteins/P77304.xmlL-Cystathionine + Water > L-Homocysteine + Ammonium + Pyruvic acidL-Cysteine + O-Succinyl-L-homoserine <> L-Cystathionine + Hydrogen ion + Succinic acidR03260O-SUCCHOMOSERLYASE-RXNL-Cystathionine + Water <> L-Homocysteine + Ammonia + Pyruvic acidR01286o-acetyl-l-homoserine + L-Cysteine <> L-Cystathionine + Acetic acidR03217O-Succinyl-L-homoserine + L-Cysteine <> L-Cystathionine + Succinic acidR03260L-Cystathionine + Water > Hydrogen ion + Pyruvic acid + Ammonia + L-HomocysteineR01286CYSTATHIONINE-BETA-LYASE-RXNL-Cysteine + O-Succinyl-L-homoserine > Hydrogen ion + Succinic acid + L-CystathionineO-SUCCHOMOSERLYASE-RXNL-Cystathionine + Water > L-Homocysteine + Ammonia + Pyruvic acidO-Succinyl-L-homoserine + L-Cysteine > L-Cystathionine + Succinic acidL-Cystathionine + Water + 2-Aminoacrylic acid + 2-Iminopropanoate <> L-Homocysteine + Pyruvic acid + AmmoniaR01286 L-Cystathionine > Hydrogen ion + Homocysteine + 2-aminoprop-2-enoate + HomocysteinePW_R002891