2.02012-05-31 13:03:22 -06002015-09-13 12:56:09 -0600ECMDB01006M2MDB000224Argininosuccinic acidArginosuccinic acid is a basic amino acid. Some cells synthesize it from citrulline, aspartic acid and use it as a precursor for arginine in the urea cycle or citrulline-NO cycle. The enzyme that catalyzes the reaction is argininosuccinate synthetase. Argininosuccinic acid is a precursor to fumarate in the citric acid cycle via argininosuccinate lyase.2-(N(Omega)-L-arginine)succinate2-(N(Omega)-L-arginine)succinic acid2-(N(Omega)-L-arginino)succinate2-(N(Omega)-L-arginino)succinic acid2-(Nw-L-arginino)butanedioate2-(Nw-L-arginino)butanedioic acidArgininosuccinateArgininosuccinic acidArginosuccinateArginosuccinic acidArgSuccinateArgSuccinic acidASAL-ArgininosuccinateL-Argininosuccinic acidL-ArginosuccinateL-Arginosuccinic acidN(Omega)-(L-arginino)succinateN(Omega)-(L-arginino)succinic acidN-(((4-Amino-4-carboxybutyl)amino)iminomethyl)-L-AspartateN-(((4-Amino-4-carboxybutyl)amino)iminomethyl)-L-Aspartic acidN-(L-Arginino) succinateN-(L-Arginino) succinic acidN-(L-Arginino)succinateN-(L-Arginino)succinic acidN-[(4-Amino-4-carboxybutyl)amidino]-L-AspartateN-[(4-Amino-4-carboxybutyl)amidino]-L-Aspartic acidN-[[(4-Amino-4-carboxybutyl)amino]iminomethyl]-L-AspartateN-[[(4-Amino-4-carboxybutyl)amino]iminomethyl]-L-Aspartic acidC10H18N4O6290.2731290.122634328(2S)-2-{N'-[(4S)-4-amino-4-carboxybutyl]carbamimidamido}butanedioic acidargininosuccinic acid2387-71-5N[C@@H](CCCNC(=N)N[C@@H](CC(O)=O)C(O)=O)C(O)=OInChI=1S/C10H18N4O6/c11-5(8(17)18)2-1-3-13-10(12)14-6(9(19)20)4-7(15)16/h5-6H,1-4,11H2,(H,15,16)(H,17,18)(H,19,20)(H3,12,13,14)/t5-,6-/m0/s1KDZOASGQNOPSCU-WDSKDSINSA-NSolidCytosollogp-3.25logs-2.80solubility4.56e-01 g/llogp-5.8pka_strongest_acidic2.14pka_strongest_basic12.39iupac(2S)-2-{N'-[(4S)-4-amino-4-carboxybutyl]carbamimidamido}butanedioic acidaverage_mass290.2731mono_mass290.122634328smilesN[C@@H](CCCNC(=N)N[C@@H](CC(O)=O)C(O)=O)C(O)=OformulaC10H18N4O6inchiInChI=1S/C10H18N4O6/c11-5(8(17)18)2-1-3-13-10(12)14-6(9(19)20)4-7(15)16/h5-6H,1-4,11H2,(H,15,16)(H,17,18)(H,19,20)(H3,12,13,14)/t5-,6-/m0/s1inchikeyKDZOASGQNOPSCU-WDSKDSINSA-Npolar_surface_area185.83refractivity75.31polarizability27.6rotatable_bond_count9acceptor_count10donor_count7physiological_charge-1formal_charge0Alanine, aspartate and glutamate metabolismec00250Arginine and proline metabolismec00330Metabolic pathwayseco01100Aspartate metabolismAspartate (seen in the center) is synthesized from and degraded to oxaloacetate , an intermediate of the TCA cycle, by a reversible transamination reaction with glutamate. As shown here, AspC is the principal transaminase that catalyzes this reaction, but TyrB also catalyzes it. Null mutations in aspC do not confer aspartate auxotrophy; null mutations in both aspC and tyrB do.
Aspartate is a constituent of proteins and participates in several other biosyntheses as shown here( NAD biosynthesis and Beta-Alanine Metabolism . Approximately 27 percent of the cell's nitrogen flows through aspartate
Aspartate can be synthesized from fumaric acid through a aspartate ammonia lyase. Aspartate also participates in the synthesis of L-asparagine through two different methods, either through aspartate ammonia ligase or asparagine synthetase B.
Aspartate is also a precursor of fumaric acid. Again it has two possible ways of synthesizing it. First set of reactions follows an adenylo succinate synthetase that yields adenylsuccinic acid and then adenylosuccinate lyase in turns leads to fumaric acid. The second way is through argininosuccinate synthase that yields argininosuccinic acid and then argininosuccinate lyase in turns leads to fumaric acid
PW000787Metabolicarginine metabolismThe metabolism of L-arginine starts with the acetylation of L-glutamic acid resulting in a N-acetylglutamic acid while releasing a coenzyme A and a hydrogen ion. N-acetylglutamic acid is then phosphorylated via an ATP driven acetylglutamate kinase which yields a N-acetyl-L-glutamyl 5-phosphate. This compound undergoes a NDPH dependent reduction resulting in N-acetyl-L-glutamate 5-semialdehyde. This compound reacts with L-glutamic acid through a acetylornithine aminotransferase / N-succinyldiaminopimelate aminotransferase to produce a N-acetylornithine which is then deacetylated through a acetylornithine deacetylase which yield an ornithine.
L-glutamine is used to synthesize carbamoyl phosphate through the interaction of L-glutamine, water, ATP, and hydrogen carbonate. This reaction yields ADP, L-glutamic acid, phosphate, and hydrogen ion.
Carbamoyl phosphate and ornithine are used to catalyze the production of citrulline through an ornithine carbamoyltransferase. Citrulline reacts with L-aspartic acid through an ATP dependent enzyme, argininosuccinate synthase to produce pyrophosphate, AMP and argininosuccinic acid. Argininosussinic acid is then lyase to produce L-arginine and fumaric acid.
L-arginine can be metabolized into succinic acid by two different sets of reactions:
1. Arginine reacts with succinyl-CoA through a arginine N-succinyltransferase resulting in N2-succinyl-L-arginine while releasing CoA and Hydrogen Ion. N2-succinyl-L-arginine is then dihydrolase to produce a N2-succinyl-L-ornithine through a N-succinylarginine dihydrolase. This compound in turn reacts with oxoglutaric acid through succinylornithine transaminase resulting in L-glutamic acid and N2-succinyl-L-glutamic acid 5-semialdehyde. This compoud in turn reacts with a NAD dependent dehydrogenase resulting in N2-succinylglutamate while releasing NADH and hydrogen ion. N2-succinylglutamate reacts with water through a succinylglutamate desuccinylase resulting in L-glutamic acid and
a succinic acid. The succinic acid is then incorporated in the TCA cycle
2.Argine reacts with carbon dioxide and a hydrogen ion through a biodegradative arginine decarboxylase, resulting in Agmatine. This compound is then transformed into putrescine by reacting with water and an agmatinase, and releasing urea. Putrescine can be metabolized by reaction with either l-glutamic acid or oxoglutaric acid. If putrescine reacts with L-glutamic acid, it reacts through an ATP mediated gamma-glutamylputrescine producing a hydrogen ion, ADP, phosphate and gamma-glutamyl-L-putrescine. This compound is reduced by interacting with oxygen, water and a gamma-glutamylputrescine oxidoreductase resulting in ammonium, hydrogen peroxide and 4-gamma-glutamylamino butanal. This compound is dehydrogenated through a NADP mediated reaction lead by gamma-glutamyl-gamma-aminobutaryaldehyde dehydrogenase resulting in hydrogen ion, NADPH and 4-glutamylamino butanoate. In turn, the latter compound reacts with water through a gamma-glutamyl-gamma-aminobutyrate hydrolase resulting in L-glutamic acid and Gamma aminobutyric acid. On the other hand, if putrescine reacts with oxoglutaric acid through a putrescine aminotransferase, it results in L-glutamic acid, and a 4-aminobutyraldehyde. This compound reacts with water through a NAD dependent gamma aminobutyraldehyde dehydrogenase resulting in hydrogen ion, NADH and gamma-aminobutyric acid.
Gamma Aaminobutyric acid reacts with oxoglutaric acid through 4-aminobutyrate aminotransferase resulting in L-glutamic acid and succinic acid semialdehyde. This compound in turn can react with with either NADP or NAD to result in the production of succinic acid through succinate-semialdehyde dehydrogenase or aldehyde dehydrogenase-like protein yneI respectively. Succinic acid can then be integrated in the TCA cycle.
L-arginine is eventua lly metabolized into succinic acid which then goes to the TCA cyclePW000790MetabolicSpecdb::CMs858Specdb::CMs11925Specdb::CMs37267Specdb::CMs134041Specdb::CMs141775Specdb::CMs1048353Specdb::CMs1048355Specdb::CMs1048356Specdb::CMs1048358Specdb::CMs1048360Specdb::CMs1048362Specdb::CMs1048364Specdb::CMs1048366Specdb::CMs1048368Specdb::CMs1048370Specdb::CMs1048372Specdb::CMs1048373Specdb::CMs1048376Specdb::CMs1048378Specdb::CMs1048379Specdb::CMs1048381Specdb::CMs1048383Specdb::CMs1048385Specdb::CMs1048387Specdb::CMs1048389Specdb::NmrOneD1054Specdb::NmrOneD250728Specdb::NmrOneD250729Specdb::NmrOneD250730Specdb::NmrOneD250731Specdb::NmrOneD250732Specdb::NmrOneD250733Specdb::NmrOneD250734Specdb::NmrOneD250735Specdb::NmrOneD250736Specdb::NmrOneD250737Specdb::NmrOneD250738Specdb::NmrOneD250739Specdb::NmrOneD250740Specdb::NmrOneD250741Specdb::NmrOneD250742Specdb::NmrOneD250743Specdb::NmrOneD250744Specdb::NmrOneD250745Specdb::NmrOneD250746Specdb::NmrOneD250747Specdb::MsMs6191Specdb::MsMs6192Specdb::MsMs6193Specdb::MsMs6194Specdb::MsMs6195Specdb::MsMs6196Specdb::MsMs6197Specdb::MsMs6198Specdb::MsMs6199Specdb::MsMs6200Specdb::MsMs6201Specdb::MsMs6202Specdb::MsMs6203Specdb::MsMs6204Specdb::MsMs6205Specdb::MsMs6206Specdb::MsMs6207Specdb::MsMs6208Specdb::MsMs292258Specdb::MsMs292259Specdb::MsMs292260Specdb::MsMs332410Specdb::MsMs332411Specdb::MsMs332412Specdb::MsMs437142Specdb::NmrTwoD1112HMDB0005243999817215918C0340615682Argininosuccinic acidKanehisa, M., Goto, S., Sato, Y., Furumichi, M., Tanabe, M. 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Kokai Tokkyo Koho (1980), 3 pp.http://hmdb.ca/system/metabolites/msds/000/000/037/original/HMDB00052.pdf?1358462827Argininosuccinate synthaseP0A6E4ASSY_ECOLIargGhttp://ecmdb.ca/proteins/P0A6E4.xmlArgininosuccinate lyaseP11447ARLY_ECOLIargHhttp://ecmdb.ca/proteins/P11447.xmlL-Aspartic acid + Adenosine triphosphate + Citrulline <> Adenosine monophosphate + Argininosuccinic acid + Hydrogen ion + PyrophosphateR01954Argininosuccinic acid <> L-Arginine + Fumaric acidR01086Adenosine triphosphate + Citrulline + L-Aspartic acid <> Adenosine monophosphate + Pyrophosphate + Argininosuccinic acidR01954Adenosine triphosphate + Citrulline + L-Aspartic acid + L-Aspartic acid > Pyrophosphate + Adenosine monophosphate + Argininosuccinic acidPW_R002649Argininosuccinic acid > Fumaric acid + L-ArgininePW_R002652L-Aspartic acid + Adenosine triphosphate + Citrulline <> Adenosine monophosphate + Argininosuccinic acid + Hydrogen ion + PyrophosphateArgininosuccinic acid <> L-Arginine + Fumaric acidL-Aspartic acid + Adenosine triphosphate + Citrulline <> Adenosine monophosphate + Argininosuccinic acid + Hydrogen ion + Pyrophosphate