Amino acid synthesis and interconversion (transamination) (Homo sapiens)

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92, 341, 11, 1815, 22, 37, 4483, 6, 271310, 274135, 40, 4310, 2728, 30, 3216, 36, 3819143, 6, 2724, 331, 17, 2535, 40, 431917, 29, 417, 12, 20, 31, 4294, 8, 2139261, 5cytosolmitochondrial matrixNAATAU GLUL decamerH2OPYRPXLP-KYAT1 1PYR-5COOHNH4+NADPHATPFOLH1B GADL1 substratesSerine biosynthesisOAAPYCR2 decamer2OGH2ONH4+PXLP-OAT(26-439) 2OGASNS dimerNH3NADPHPXLP ASNS GOT2 dimerNAALAD2 ADPGADL1 PiPXLP-GOT2 H+GOT1 dimerALDH18A1-2 L-GlnGLUL L-ProOAT hexamerNADH NAALADasesL-GluASPGL-OrnP5CS dimersNADP+ L-GluL-AspASPA:Zn2+ dimerL-Asp2OGL-AsnRIMKLB NAD(P)+L-GlnGLS dimersGOT1 GLUD1 GTPNADP+Ac-CoANAD(P)HL-Asp CoA-SHGPT2 dimer2OGL-GluH2ONAD+AMPNADHGADL1 productsH2OH2OL-GlnNADPH 1PYR-5COOHNADP+PYCR1 H+OARIMKLA H+PiFOLH1 ADPL-GluPXLP-KYAT1 dimerGPT2-1 L-AlaASPA L-Glu5SZn2+ GLUD2 ALDH18A1-1 CYSA 2OGANAASPL-GluNH4+GLS2 GADL1:PXLPPYCR2 L-AlaATPCH3COO-CSA ATPCO2L-ProL-GluNAT8LPPiPYRHTAU RIMKLA, RIMKLBNAANAAGb-Ala PYCR1 decamerADPH+H+L-AspGPT dimerGLUD hexamerGLS PXLP ATPPYCRL PYCRL decamerADPPXLP-GPT NAD+ 112622, 371735192365914333122, 37, 446


Description

These reactions mediate the synthesis of aspartate, asparagine, glutamate, and glutamine from ammonia and intermediates of glycolysis, and allow the utilization of the carbon atoms from these four amino acids for glucose synthesis under fasting conditions.

These reactions also provide a means to collect nitrogen, both as ammonia and as amino groups, and direct it towards urea synthesis. Transamination, the conversion of an amino acid to the corresponding alpha-keto acid coupled to the conversion of a molecule of alpha-ketoglutarate to glutamate, is the first step in the catabolism of most amino acids. Transamination reactions are freely reversible so they also provide a means to balance concentrations of various amino acids and alpha-keto (2-oxo) acids in the cytosol. View original pathway at:Reactome.</div>

Comments

Reactome-Converter 
Pathway is converted from Reactome ID: 70614
Reactome-version 
Reactome version: 66

Quality Tags

Ontology Terms

 

Bibliography

View all...
  1. De Ingeniis J, Ratnikov B, Richardson AD, Scott DA, Aza-Blanc P, De SK, Kazanov M, Pellecchia M, Ronai Z, Osterman AL, Smith JW.; ''Functional specialization in proline biosynthesis of melanoma.''; PubMed Europe PMC
  2. Liu P, Ge X, Ding H, Jiang H, Christensen BM, Li J.; ''Role of glutamate decarboxylase-like protein 1 (GADL1) in taurine biosynthesis.''; PubMed Europe PMC
  3. Sohocki MM, Sullivan LS, Harrison WR, Sodergren EJ, Elder FF, Weinstock G, Tanase S, Daiger SP.; ''Human glutamate pyruvate transaminase (GPT): localization to 8q24.3, cDNA and genomic sequences, and polymorphic sites.''; PubMed Europe PMC
  4. Wiame E, Tyteca D, Pierrot N, Collard F, Amyere M, Noel G, Desmedt J, Nassogne MC, Vikkula M, Octave JN, Vincent MF, Courtoy PJ, Boltshauser E, van Schaftingen E.; ''Molecular identification of aspartate N-acetyltransferase and its mutation in hypoacetylaspartia.''; PubMed Europe PMC
  5. Merrill MJ, Yeh GC, Phang JM.; ''Purified human erythrocyte pyrroline-5-carboxylate reductase. Preferential oxidation of NADPH.''; PubMed Europe PMC
  6. Ishiguro M, Takio K, Suzuki M, Oyama R, Matsuzawa T, Titani K.; ''Complete amino acid sequence of human liver cytosolic alanine aminotransferase (GPT) determined by a combination of conventional and mass spectral methods.''; PubMed Europe PMC
  7. Pangalos MN, Neefs JM, Somers M, Verhasselt P, Bekkers M, van der Helm L, Fraiponts E, Ashton D, Gordon RD.; ''Isolation and expression of novel human glutamate carboxypeptidases with N-acetylated alpha-linked acidic dipeptidase and dipeptidyl peptidase IV activity.''; PubMed Europe PMC
  8. Prokesch A, Pelzmann HJ, Pessentheiner AR, Huber K, Madreiter-Sokolowski CT, Drougard A, Schittmayer M, Kolb D, Magnes C, Trausinger G, Graier WF, Birner-Gruenberger R, Pospisilik JA, Bogner-Strauss JG.; ''N-acetylaspartate catabolism determines cytosolic acetyl-CoA levels and histone acetylation in brown adipocytes.''; PubMed Europe PMC
  9. Martini F, Angelaccio S, Barra D, Pascarella S, Maras B, Doonan S, Bossa F.; ''The primary structure of mitochondrial aspartate aminotransferase from human heart.''; PubMed Europe PMC
  10. Glinghammar B, Rafter I, Lindström AK, Hedberg JJ, Andersson HB, Lindblom P, Berg AL, Cotgreave I.; ''Detection of the mitochondrial and catalytically active alanine aminotransferase in human tissues and plasma.''; PubMed Europe PMC
  11. Meng Z, Lou Z, Liu Z, Li M, Zhao X, Bartlam M, Rao Z.; ''Crystal structure of human pyrroline-5-carboxylate reductase.''; PubMed Europe PMC
  12. Hlouchova K, Barinka C, Konvalinka J, Lubkowski J.; ''Structural insight into the evolutionary and pharmacologic homology of glutamate carboxypeptidases II and III.''; PubMed Europe PMC
  13. Karamitros CS, Konrad M.; ''Human 60-kDa lysophospholipase contains an N-terminal L-asparaginase domain that is allosterically regulated by L-asparagine.''; PubMed Europe PMC
  14. Collard F, Stroobant V, Lamosa P, Kapanda CN, Lambert DM, Muccioli GG, Poupaert JH, Opperdoes F, Van Schaftingen E.; ''Molecular identification of N-acetylaspartylglutamate synthase and beta-citrylglutamate synthase.''; PubMed Europe PMC
  15. Perry S, Harries H, Scholfield C, Lock T, King L, Gibson G, Goldfarb P.; ''Molecular cloning and expression of a cDNA for human kidney cysteine conjugate beta-lyase.''; PubMed Europe PMC
  16. Bitto E, Bingman CA, Wesenberg GE, McCoy JG, Phillips GN.; ''Structure of aspartoacylase, the brain enzyme impaired in Canavan disease.''; PubMed Europe PMC
  17. Shen BW, Hennig M, Hohenester E, Jansonius JN, Schirmer T.; ''Crystal structure of human recombinant ornithine aminotransferase.''; PubMed Europe PMC
  18. Reversade B, Escande-Beillard N, Dimopoulou A, Fischer B, Chng SC, Li Y, Shboul M, Tham PY, Kayserili H, Al-Gazali L, Shahwan M, Brancati F, Lee H, O'Connor BD, Schmidt-von Kegler M, Merriman B, Nelson SF, Masri A, Alkazaleh F, Guerra D, Ferrari P, Nanda A, Rajab A, Markie D, Gray M, Nelson J, Grix A, Sommer A, Savarirayan R, Janecke AR, Steichen E, Sillence D, Hausser I, Budde B, Nürnberg G, Nürnberg P, Seemann P, Kunkel D, Zambruno G, Dallapiccola B, Schuelke M, Robertson S, Hamamy H, Wollnik B, Van Maldergem L, Mundlos S, Kornak U.; ''Mutations in PYCR1 cause cutis laxa with progeroid features.''; PubMed Europe PMC
  19. Doyle JM, Schininà ME, Bossa F, Doonan S.; ''The amino acid sequence of cytosolic aspartate aminotransferase from human liver.''; PubMed Europe PMC
  20. O'Keefe DS, Bacich DJ, Heston WD.; ''Comparative analysis of prostate-specific membrane antigen (PSMA) versus a prostate-specific membrane antigen-like gene.''; PubMed Europe PMC
  21. Pessentheiner AR, Pelzmann HJ, Walenta E, Schweiger M, Groschner LN, Graier WF, Kolb D, Uno K, Miyazaki T, Nitta A, Rieder D, Prokesch A, Bogner-Strauss JG.; ''NAT8L (N-acetyltransferase 8-like) accelerates lipid turnover and increases energy expenditure in brown adipocytes.''; PubMed Europe PMC
  22. Han Q, Robinson H, Cai T, Tagle DA, Li J.; ''Structural insight into the inhibition of human kynurenine aminotransferase I/glutamine transaminase K.''; PubMed Europe PMC
  23. de Koning TJ, Klomp LW.; ''Serine-deficiency syndromes.''; PubMed Europe PMC
  24. Häberle J, Görg B, Rutsch F, Schmidt E, Toutain A, Benoist JF, Gelot A, Suc AL, Höhne W, Schliess F, Häussinger D, Koch HG.; ''Congenital glutamine deficiency with glutamine synthetase mutations.''; PubMed Europe PMC
  25. Nakayama T, Al-Maawali A, El-Quessny M, Rajab A, Khalil S, Stoler JM, Tan WH, Nasir R, Schmitz-Abe K, Hill RS, Partlow JN, Al-Saffar M, Servattalab S, LaCoursiere CM, Tambunan DE, Coulter ME, Elhosary PC, Gorski G, Barkovich AJ, Markianos K, Poduri A, Mochida GH.; ''Mutations in PYCR2, Encoding Pyrroline-5-Carboxylate Reductase 2, Cause Microcephaly and Hypomyelination.''; PubMed Europe PMC
  26. Van Heeke G, Schuster SM.; ''Expression of human asparagine synthetase in Escherichia coli.''; PubMed Europe PMC
  27. Yang RZ, Blaileanu G, Hansen BC, Shuldiner AR, Gong DW.; ''cDNA cloning, genomic structure, chromosomal mapping, and functional expression of a novel human alanine aminotransferase.''; PubMed Europe PMC
  28. Quesada AR, Sanchez-Jimenez F, Perez-Rodriguez J, Marquez J, Medina MA, Nuñez de Castro I.; ''Purification of phosphate-dependent glutaminase from isolated mitochondria of Ehrlich ascites-tumour cells.''; PubMed Europe PMC
  29. Ohura T, Kominami E, Tada K, Katunuma N.; ''Crystallization and properties of human liver ornithine aminotransferase.''; PubMed Europe PMC
  30. Elgadi KM, Meguid RA, Qian M, Souba WW, Abcouwer SF.; ''Cloning and analysis of unique human glutaminase isoforms generated by tissue-specific alternative splicing.''; PubMed Europe PMC
  31. Mesters JR, Barinka C, Li W, Tsukamoto T, Majer P, Slusher BS, Konvalinka J, Hilgenfeld R.; ''Structure of glutamate carboxypeptidase II, a drug target in neuronal damage and prostate cancer.''; PubMed Europe PMC
  32. Gómez-Fabre PM, Aledo JC, Del Castillo-Olivares A, Alonso FJ, Núñez De Castro I, Campos JA, Márquez J.; ''Molecular cloning, sequencing and expression studies of the human breast cancer cell glutaminase.''; PubMed Europe PMC
  33. Krajewski WW, Collins R, Holmberg-Schiavone L, Jones TA, Karlberg T, Mowbray SL.; ''Crystal structures of mammalian glutamine synthetases illustrate substrate-induced conformational changes and provide opportunities for drug and herbicide design.''; PubMed Europe PMC
  34. Liu P, Torrens-Spence MP, Ding H, Christensen BM, Li J.; ''Mechanism of cysteine-dependent inactivation of aspartate/glutamate/cysteine sulfinic acid α-decarboxylases.''; PubMed Europe PMC
  35. Julliard JH, Smith EL.; ''Partial amino acid sequence of the glutamate dehydrogenase of human liver and a revision of the sequence of the bovine enzyme.''; PubMed Europe PMC
  36. Le Coq J, An HJ, Lebrilla C, Viola RE.; ''Characterization of human aspartoacylase: the brain enzyme responsible for Canavan disease.''; PubMed Europe PMC
  37. Rossi F, Han Q, Li J, Li J, Rizzi M.; ''Crystal structure of human kynurenine aminotransferase I.''; PubMed Europe PMC
  38. Herga S, Berrin JG, Perrier J, Puigserver A, Giardina T.; ''Identification of the zinc binding ligands and the catalytic residue in human aspartoacylase, an enzyme involved in Canavan disease.''; PubMed Europe PMC
  39. Hu CA, Lin WW, Obie C, Valle D.; ''Molecular enzymology of mammalian Delta1-pyrroline-5-carboxylate synthase. Alternative splice donor utilization generates isoforms with different sensitivity to ornithine inhibition.''; PubMed Europe PMC
  40. Fang J, Hsu BY, MacMullen CM, Poncz M, Smith TJ, Stanley CA.; ''Expression, purification and characterization of human glutamate dehydrogenase (GDH) allosteric regulatory mutations.''; PubMed Europe PMC
  41. Brody LC, Mitchell GA, Obie C, Michaud J, Steel G, Fontaine G, Robert MF, Sipila I, Kaiser-Kupfer M, Valle D.; ''Ornithine delta-aminotransferase mutations in gyrate atrophy. Allelic heterogeneity and functional consequences.''; PubMed Europe PMC
  42. Wozniak KM, Rojas C, Wu Y, Slusher BS.; ''The role of glutamate signaling in pain processes and its regulation by GCP II inhibition.''; PubMed Europe PMC
  43. Smith TJ, Schmidt T, Fang J, Wu J, Siuzdak G, Stanley CA.; ''The structure of apo human glutamate dehydrogenase details subunit communication and allostery.''; PubMed Europe PMC
  44. Baran H, Okuno E, Kido R, Schwarcz R.; ''Purification and characterization of kynurenine aminotransferase I from human brain.''; PubMed Europe PMC

History

View all...
CompareRevisionActionTimeUserComment
101258view11:15, 1 November 2018ReactomeTeamreactome version 66
100796view20:42, 31 October 2018ReactomeTeamreactome version 65
100338view19:20, 31 October 2018ReactomeTeamreactome version 64
99883view16:03, 31 October 2018ReactomeTeamreactome version 63
99440view14:37, 31 October 2018ReactomeTeamreactome version 62 (2nd attempt)
99111view12:39, 31 October 2018ReactomeTeamreactome version 62
93938view13:46, 16 August 2017ReactomeTeamreactome version 61
93527view11:26, 9 August 2017ReactomeTeamreactome version 61
87082view14:23, 18 July 2016MkutmonOntology Term : 'amino acid metabolic pathway' added !
86626view09:22, 11 July 2016ReactomeTeamreactome version 56
83454view12:26, 18 November 2015ReactomeTeamNew pathway

External references

DataNodes

View all...
NameTypeDatabase referenceComment
1PYR-5COOHMetaboliteCHEBI:17388 (ChEBI)
2OGAMetaboliteCHEBI:30882 (ChEBI)
2OGMetaboliteCHEBI:30915 (ChEBI)
ADPMetaboliteCHEBI:16761 (ChEBI)
ALDH18A1-1 ProteinP54886-1 (Uniprot-TrEMBL)
ALDH18A1-2 ProteinP54886-2 (Uniprot-TrEMBL)
AMPMetaboliteCHEBI:16027 (ChEBI)
ASNS ProteinP08243 (Uniprot-TrEMBL)
ASNS dimerComplexR-HSA-507865 (Reactome)
ASPA ProteinP45381 (Uniprot-TrEMBL)
ASPA:Zn2+ dimerComplexR-HSA-5692213 (Reactome)
ASPGProteinQ86U10 (Uniprot-TrEMBL)
ATPMetaboliteCHEBI:15422 (ChEBI)
Ac-CoAMetaboliteCHEBI:15351 (ChEBI)
CH3COO-MetaboliteCHEBI:15366 (ChEBI)
CO2MetaboliteCHEBI:16526 (ChEBI)
CSA MetaboliteCHEBI:16345 (ChEBI)
CYSA MetaboliteCHEBI:17285 (ChEBI)
CoA-SHMetaboliteCHEBI:15346 (ChEBI)
FOLH1 ProteinQ04609 (Uniprot-TrEMBL)
FOLH1B ProteinQ9HBA9 (Uniprot-TrEMBL)
GADL1 ProteinQ6ZQY3 (Uniprot-TrEMBL)
GADL1 productsComplexR-ALL-6787762 (Reactome)
GADL1 substratesComplexR-ALL-6787759 (Reactome)
GADL1:PXLPComplexR-HSA-6787755 (Reactome)
GLS ProteinO94925 (Uniprot-TrEMBL)
GLS dimersComplexR-HSA-507859 (Reactome)
GLS2 ProteinQ9UI32 (Uniprot-TrEMBL)
GLUD hexamerComplexR-HSA-70583 (Reactome)
GLUD1 ProteinP00367 (Uniprot-TrEMBL)
GLUD2 ProteinP49448 (Uniprot-TrEMBL)
GLUL ProteinP15104 (Uniprot-TrEMBL)
GLUL decamerComplexR-HSA-70604 (Reactome)
GOT1 ProteinP17174 (Uniprot-TrEMBL)
GOT1 dimerComplexR-HSA-70579 (Reactome)
GOT2 dimerComplexR-HSA-70594 (Reactome)
GPT dimerComplexR-HSA-70521 (Reactome)
GPT2 dimerComplexR-HSA-507753 (Reactome)
GPT2-1 ProteinQ8TD30-1 (Uniprot-TrEMBL)
GTPMetaboliteCHEBI:15996 (ChEBI)
H+MetaboliteCHEBI:15378 (ChEBI)
H2OMetaboliteCHEBI:15377 (ChEBI)
HTAU MetaboliteCHEBI:16668 (ChEBI)
L-AlaMetaboliteCHEBI:57972 (ChEBI)
L-AsnMetaboliteCHEBI:58048 (ChEBI)
L-Asp MetaboliteCHEBI:29991 (ChEBI)
L-AspMetaboliteCHEBI:29991 (ChEBI)
L-GlnMetaboliteCHEBI:58359 (ChEBI)
L-Glu5SMetaboliteCHEBI:17232 (ChEBI)
L-GluMetaboliteCHEBI:29985 (ChEBI)
L-OrnMetaboliteCHEBI:15729 (ChEBI)
L-ProMetaboliteCHEBI:60039 (ChEBI)
NAAMetaboliteCHEBI:21547 (ChEBI)
NAAGMetaboliteCHEBI:76931 (ChEBI)
NAALAD2 ProteinQ9Y3Q0 (Uniprot-TrEMBL)
NAALADasesComplexR-HSA-6787341 (Reactome)
NAASPMetaboliteCHEBI:16953 (ChEBI)
NAD(P)+ComplexR-ALL-517495 (Reactome)
NAD(P)HComplexR-ALL-517496 (Reactome)
NAD+ MetaboliteCHEBI:15846 (ChEBI)
NAD+MetaboliteCHEBI:15846 (ChEBI)
NADH MetaboliteCHEBI:16908 (ChEBI)
NADHMetaboliteCHEBI:16908 (ChEBI)
NADP+ MetaboliteCHEBI:18009 (ChEBI)
NADP+MetaboliteCHEBI:18009 (ChEBI)
NADPH MetaboliteCHEBI:16474 (ChEBI)
NADPHMetaboliteCHEBI:16474 (ChEBI)
NAT8LProteinQ8N9F0 (Uniprot-TrEMBL)
NH3MetaboliteCHEBI:16134 (ChEBI)
NH4+MetaboliteCHEBI:28938 (ChEBI)
OAAMetaboliteCHEBI:30744 (ChEBI)
OAMetaboliteCHEBI:30744 (ChEBI)
OAT hexamerComplexR-HSA-70639 (Reactome)
P5CS dimersComplexR-HSA-508070 (Reactome)
PPiMetaboliteCHEBI:29888 (ChEBI)
PXLP MetaboliteCHEBI:18405 (ChEBI)
PXLP-GOT2 ProteinP00505 (Uniprot-TrEMBL)
PXLP-GPT ProteinP24298 (Uniprot-TrEMBL)
PXLP-KYAT1 ProteinQ16773 (Uniprot-TrEMBL)
PXLP-KYAT1 dimerComplexR-HSA-893603 (Reactome)
PXLP-OAT(26-439) ProteinP04181 (Uniprot-TrEMBL)
PYCR1 ProteinP32322 (Uniprot-TrEMBL)
PYCR1 decamerComplexR-HSA-70662 (Reactome)
PYCR2 ProteinQ96C36 (Uniprot-TrEMBL)
PYCR2 decamerComplexR-HSA-6783952 (Reactome)
PYCRL ProteinQ53H96 (Uniprot-TrEMBL)
PYCRL decamerComplexR-HSA-6783932 (Reactome)
PYRMetaboliteCHEBI:32816 (ChEBI)
PiMetaboliteCHEBI:18367 (ChEBI)
RIMKLA ProteinQ8IXN7 (Uniprot-TrEMBL)
RIMKLA, RIMKLBComplexR-HSA-8942565 (Reactome)
RIMKLB ProteinQ9ULI2 (Uniprot-TrEMBL)
Serine biosynthesisPathwayR-HSA-977347 (Reactome) L-Serine is needed in human brain in large amounts as precursor to important biomolecules such as nucleotides, phospholipids and the neurotransmitters glycine and D-serine. The pathway for its synthesis starts with 3-phosphoglycerate and it later needs glutamate as an amination agent. Deficiencies in the participating enzymes lead to severe neurological symptoms that are treatable with serine if treatment starts early (de Koning & Klomp 2004).
TAU MetaboliteCHEBI:15891 (ChEBI)
Zn2+ MetaboliteCHEBI:29105 (ChEBI)
b-Ala MetaboliteCHEBI:16958 (ChEBI)

Annotated Interactions

View all...
SourceTargetTypeDatabase referenceComment
1PYR-5COOHArrowR-HSA-70655 (Reactome)
1PYR-5COOHR-HSA-6783939 (Reactome)
1PYR-5COOHR-HSA-6783955 (Reactome)
1PYR-5COOHR-HSA-70664 (Reactome)
2OGAArrowR-HSA-893616 (Reactome)
2OGArrowR-HSA-507749 (Reactome)
2OGArrowR-HSA-70524 (Reactome)
2OGArrowR-HSA-70581 (Reactome)
2OGArrowR-HSA-70600 (Reactome)
2OGArrowR-HSA-70613 (Reactome)
2OGArrowR-HSA-70666 (Reactome)
2OGR-HSA-507775 (Reactome)
2OGR-HSA-70523 (Reactome)
2OGR-HSA-70589 (Reactome)
2OGR-HSA-70592 (Reactome)
2OGR-HSA-70596 (Reactome)
2OGR-HSA-70654 (Reactome)
ADPArrowR-HSA-508040 (Reactome)
ADPArrowR-HSA-70589 (Reactome)
ADPArrowR-HSA-70600 (Reactome)
ADPArrowR-HSA-70606 (Reactome)
ADPArrowR-HSA-8942575 (Reactome)
AMPArrowR-HSA-70599 (Reactome)
ASNS dimermim-catalysisR-HSA-70599 (Reactome)
ASPA:Zn2+ dimermim-catalysisR-HSA-5691507 (Reactome)
ASPGmim-catalysisR-HSA-6797627 (Reactome)
ATPR-HSA-508040 (Reactome)
ATPR-HSA-70599 (Reactome)
ATPR-HSA-70606 (Reactome)
ATPR-HSA-8942575 (Reactome)
Ac-CoAR-HSA-8954468 (Reactome)
CH3COO-ArrowR-HSA-5691507 (Reactome)
CO2ArrowR-HSA-6787757 (Reactome)
CoA-SHArrowR-HSA-8954468 (Reactome)
GADL1 productsArrowR-HSA-6787757 (Reactome)
GADL1 substratesR-HSA-6787757 (Reactome)
GADL1:PXLPmim-catalysisR-HSA-6787757 (Reactome)
GLS dimersmim-catalysisR-HSA-70609 (Reactome)
GLUD hexamermim-catalysisR-HSA-70589 (Reactome)
GLUD hexamermim-catalysisR-HSA-70600 (Reactome)
GLUL decamermim-catalysisR-HSA-70606 (Reactome)
GOT1 dimermim-catalysisR-HSA-70581 (Reactome)
GOT1 dimermim-catalysisR-HSA-70592 (Reactome)
GOT2 dimermim-catalysisR-HSA-70596 (Reactome)
GOT2 dimermim-catalysisR-HSA-70613 (Reactome)
GPT dimermim-catalysisR-HSA-70523 (Reactome)
GPT dimermim-catalysisR-HSA-70524 (Reactome)
GPT2 dimermim-catalysisR-HSA-507749 (Reactome)
GPT2 dimermim-catalysisR-HSA-507775 (Reactome)
GTPTBarR-HSA-70589 (Reactome)
GTPTBarR-HSA-70600 (Reactome)
H+ArrowR-HSA-70600 (Reactome)
H+ArrowR-HSA-8954468 (Reactome)
H+R-HSA-508040 (Reactome)
H+R-HSA-6783939 (Reactome)
H+R-HSA-6783955 (Reactome)
H+R-HSA-70589 (Reactome)
H+R-HSA-70664 (Reactome)
H2OArrowR-HSA-70589 (Reactome)
H2OArrowR-HSA-70655 (Reactome)
H2OR-HSA-5691507 (Reactome)
H2OR-HSA-6797627 (Reactome)
H2OR-HSA-70599 (Reactome)
H2OR-HSA-70600 (Reactome)
H2OR-HSA-70609 (Reactome)
L-AlaArrowR-HSA-507749 (Reactome)
L-AlaArrowR-HSA-70524 (Reactome)
L-AlaArrowR-HSA-893616 (Reactome)
L-AlaR-HSA-507775 (Reactome)
L-AlaR-HSA-70523 (Reactome)
L-AsnArrowR-HSA-70599 (Reactome)
L-AsnR-HSA-6797627 (Reactome)
L-AspArrowR-HSA-5691507 (Reactome)
L-AspArrowR-HSA-6797627 (Reactome)
L-AspArrowR-HSA-70581 (Reactome)
L-AspArrowR-HSA-70613 (Reactome)
L-AspR-HSA-70592 (Reactome)
L-AspR-HSA-70596 (Reactome)
L-AspR-HSA-70599 (Reactome)
L-AspR-HSA-8954468 (Reactome)
L-GlnArrowR-HSA-70606 (Reactome)
L-GlnR-HSA-70599 (Reactome)
L-GlnR-HSA-70609 (Reactome)
L-GlnR-HSA-893616 (Reactome)
L-Glu5SArrowR-HSA-508040 (Reactome)
L-Glu5SArrowR-HSA-70654 (Reactome)
L-Glu5SR-HSA-70655 (Reactome)
L-Glu5SR-HSA-70666 (Reactome)
L-GluArrowR-HSA-507775 (Reactome)
L-GluArrowR-HSA-5693783 (Reactome)
L-GluArrowR-HSA-70523 (Reactome)
L-GluArrowR-HSA-70589 (Reactome)
L-GluArrowR-HSA-70592 (Reactome)
L-GluArrowR-HSA-70596 (Reactome)
L-GluArrowR-HSA-70599 (Reactome)
L-GluArrowR-HSA-70609 (Reactome)
L-GluArrowR-HSA-70654 (Reactome)
L-GluR-HSA-507749 (Reactome)
L-GluR-HSA-508040 (Reactome)
L-GluR-HSA-70524 (Reactome)
L-GluR-HSA-70581 (Reactome)
L-GluR-HSA-70600 (Reactome)
L-GluR-HSA-70606 (Reactome)
L-GluR-HSA-70613 (Reactome)
L-GluR-HSA-70666 (Reactome)
L-GluR-HSA-8942575 (Reactome)
L-OrnArrowR-HSA-70666 (Reactome)
L-OrnR-HSA-70654 (Reactome)
L-ProArrowR-HSA-6783939 (Reactome)
L-ProArrowR-HSA-6783955 (Reactome)
L-ProArrowR-HSA-70664 (Reactome)
NAAArrowR-HSA-8954468 (Reactome)
NAAArrowR-HSA-8954513 (Reactome)
NAAGArrowR-HSA-8942575 (Reactome)
NAAGR-HSA-5693783 (Reactome)
NAALADasesmim-catalysisR-HSA-5693783 (Reactome)
NAAR-HSA-5691507 (Reactome)
NAAR-HSA-8942575 (Reactome)
NAAR-HSA-8954513 (Reactome)
NAASPArrowR-HSA-5693783 (Reactome)
NAD(P)+ArrowR-HSA-70589 (Reactome)
NAD(P)+R-HSA-70600 (Reactome)
NAD(P)HArrowR-HSA-70600 (Reactome)
NAD(P)HR-HSA-70589 (Reactome)
NAD+ArrowR-HSA-6783939 (Reactome)
NAD+ArrowR-HSA-70664 (Reactome)
NADHR-HSA-6783939 (Reactome)
NADHR-HSA-70664 (Reactome)
NADP+ArrowR-HSA-508040 (Reactome)
NADP+ArrowR-HSA-6783955 (Reactome)
NADPHR-HSA-508040 (Reactome)
NADPHR-HSA-6783955 (Reactome)
NAT8Lmim-catalysisR-HSA-8954468 (Reactome)
NH3ArrowR-HSA-6797627 (Reactome)
NH4+ArrowR-HSA-70600 (Reactome)
NH4+ArrowR-HSA-70609 (Reactome)
NH4+R-HSA-70589 (Reactome)
NH4+R-HSA-70606 (Reactome)
OAAArrowR-HSA-70596 (Reactome)
OAAR-HSA-70613 (Reactome)
OAArrowR-HSA-70592 (Reactome)
OAR-HSA-70581 (Reactome)
OAT hexamermim-catalysisR-HSA-70654 (Reactome)
OAT hexamermim-catalysisR-HSA-70666 (Reactome)
P5CS dimersmim-catalysisR-HSA-508040 (Reactome)
PPiArrowR-HSA-70599 (Reactome)
PXLP-KYAT1 dimermim-catalysisR-HSA-893616 (Reactome)
PYCR1 decamermim-catalysisR-HSA-70664 (Reactome)
PYCR2 decamermim-catalysisR-HSA-6783939 (Reactome)
PYCRL decamermim-catalysisR-HSA-6783955 (Reactome)
PYRArrowR-HSA-507775 (Reactome)
PYRArrowR-HSA-70523 (Reactome)
PYRR-HSA-507749 (Reactome)
PYRR-HSA-70524 (Reactome)
PYRR-HSA-893616 (Reactome)
PiArrowR-HSA-508040 (Reactome)
PiArrowR-HSA-70606 (Reactome)
R-HSA-507749 (Reactome) Glutamic-pyruvate transaminase 2 (alanine aminotransferase 2) (GPT2) catalyzes the reversible reaction of pyruvate and glutamate to form alanine and 2-oxoglutarate (alpha-ketoglutarate) (Yang et al. 2002). Unpublished crystallographic data are consistent with a homodimeric structure for the enzyme with one molecule of pyridoxal phosphate associated with each monomer (PDB 3IHJ). Recent studies of organelles purified from cultured human muscle cells suggest that GPT2 is localized to mitochondria (Glinghammar et al. 2009).
R-HSA-507775 (Reactome) Glutamic-pyruvate transaminase 2 (alanine aminotransferase 2) (GPT2) catalyzes the reversible reaction of alanine and 2-oxoglutarate (alpha-ketoglutarate) to form pyruvate and glutamate (Yang et al. 2002). Unpublished crystallographic data are consistent with a homodimeric structure for the enzyme with one molecule of pyridoxal phosphate associated with each monomer (PDB 3IHJ). Recent studies of organelles purified from cultured human muscle cells suggest that GPT2 is localized to mitochondria (Glinghammar et al. 2009).
R-HSA-508040 (Reactome) Delta-1-pyrroline-5-carboxylate synthetase associated with the inner mitochondrial membrane catalyzes the two-step reaction that converts glutamate, ATP, and NADPH + H+ to L-glutamate gamma-semialdehyde, NADP+, ADP, and orthophosphate. Two P5CS isoforms have been identified; both are active when expressed in enzyme-deficient cells in culture (Hu et al. 1999). Unpublished crystallographic data (PDB 2H5G) indicate that the enzyme is a dimer.
R-HSA-5691507 (Reactome) Aspartoacylase (ASPA) is a cytosolic zinc metalloenzyme highly expressed in brain white matter, skeletal muscle, kidney, adrenal glands, lung and liver. ASPA catalyses the hydrolysis of N-acetylaspartic acid (NAA) to produce acetate (CH3COO-) and L-aspartate (L-Asp). NAA occurs in high concentration in brain and is thought to play a significant part in the maintenance of intact white matter. In other tissues it acts as a scavenger of NAA from body fluids. Defects in ASPA lead to Canavan disease (CAND; MIM:271900), a fatal neurological disorder of infants characterised by white matter vacuolisation and demyelination (Herga et al. 2006, Le Coq et al. 2006, Bitto et al. 2007).
R-HSA-5693783 (Reactome) Excessive glutamate has been implicated in neurodegenerative disorders and stroke. One source of glutamate is from the hydrolysis of N-acetylaspartylglutamate (NAAG), a neurotransmitter found in the brain. NAAG can he hydrolysed by glutamate carboxypeptidase 2 (FOLH1), a membrane-bound, homodimeric enzyme which possesses both folate hydrolase and N-acetylated-alpha-linked-acidic dipeptidase (NAALADase) activity (Mesters et al. 2006). Inhibition of FOLH1 could have neuroprotective effects (Wozniak et al. 2012). Other dipeptidases able to hydrolyse NAAG are N-acetylated-alpha-linked acidic dipeptidase 2 (NAALAD2) (Pangalos et al. 1999, Hlouchova et al. 2009) and putative N-acetylated-alpha-linked acidic dipeptidase (FOLH1B) (O'Keefe et al. 2004).
R-HSA-6783939 (Reactome) Pyrroline-5-carboxylate reductase 2 (PYCR2) catalyzes the reaction of (S)-1-pyrroline-5-carboxylate with NADH + H+ to form proline and NAD+ (De Ingeniis et al. 2012). The active enzyme is inferred to be a homodecamer by virtue of its similarity to PYCR1 (Meng et al. 2006). Subcellular fractionation (De Ingeniis et al. 2012) and co-localization studies (Nakayama et al. 2015) indicate that PYCR1 is mitochondrial. Its deficiency is associated with microcephaly and hypomyelination (Nakayama et al. 2015).
R-HSA-6783955 (Reactome) Pyrroline-5-carboxylate reductase-like (PYCRL) catalyzes the reaction of (S)-1-pyrroline-5-carboxylate with NADPH + H+ to form proline and NADP+ in the cytosol (De Ingeniis et al. 2012). While the pyrroline-5-carboxylate reductase described by Merrill et al. (1989) is taken to be the PYCR1 or PYCR2 gene product, its abundance in red blood cell cytosol and its strong preference for NADP as a cofactor suggest the alternative interpretation that it is the product of PYCRL.
R-HSA-6787757 (Reactome) Acidic amino acid decarboxylase GADL1 (GADL1) can decarboxylate aspartate, cysteine sulfinic acid, and cysteic acid to beta-alanine, hypotaurine and taurine, respectively but does not exhibit any decarboxylation activity toward glutamate (Liu et al. 2012, 2013).
R-HSA-6797627 (Reactome) L-Asparaginases can catalyse the hydrolysis of L-asparagine (L-Asn) to L-aspartic acid (L-Asp) and ammonia (NH3) in organisms ranging from bacteria to humans. Bacterial type II versions of the enzyme serve as therapeutics for the treatment of acute lymphoblastic leukemia despite adverse side effects. The human equivalent (60 kDa lysophospholipase, ASPG) has shown to possess L-Asparaginase activity and may be a potential alternative replacement for bacterial enzymes as a leukemia therapeutic in the future (Karamitros & Konrad 2014).
R-HSA-70523 (Reactome) Cytosolic glutamic-pyruvate transaminase (alanine aminotransferase) (GPT) catalyzes the reversible reaction of alanine and 2-oxoglutarate (alpha-ketoglutarate) to form pyruvate and glutamate (Sohocki et al. 1997; Yang et al. 2002). The active form of the enzyme is a dimer (Ishiguro et al. 1991) and is inferred to have a molecule of pyridoxal phosphate associated with each monomer. This reaction allows the synthesis of alanine from intermediates of glucose metabolism in a well-fed person. Under fasting conditions, alanine, derived from protein breakdown, can be converted to pyruvate and used to synthesize glucose via the gluconeogenic pathway in liver, or fully oxidized via the TCA cycle in other tissues.
R-HSA-70524 (Reactome) Cytosolic glutamic-pyruvate transaminase (alanine aminotransferase) (GPT) catalyzes the reversible reaction of pyruvate and glutamate to form alanine and 2-oxoglutarate (alpha-ketoglutarate) (Sohocki et al. 1997; Yang et al. 2002). The active form of the enzyme is a dimer (Ishiguro et al. 1991) and is inferred to have a molecule of pyridoxal phosphate associated with each monomer. This reaction allows the synthesis of alanine from intermediates of glucose metabolism in a well-fed person. Under fasting conditions, alanine, derived from protein breakdown, can be converted to pyruvate and used to synthesize glucose via the gluconeogenic pathway in liver, or fully oxidized via the TCA cycle in other tissues.
R-HSA-70581 (Reactome) Cytosolic aspartate aminotransferase (glutamate oxaloacetate transaminase 1 - GOT1) catalyzes the reversible reaction of oxaloacetate and glutamate to form aspartate and 2-oxoglutarate (alpha-ketoglutarate) (Doyle et al. 1990). Unpublished crystallographic data (PBD 3IIO) suggest the enzyme is a homodimer.
R-HSA-70589 (Reactome) Mitochondrial glutamate dehydrogenase 1 (GLUD1) catalyzes the reversible reaction of 2-oxoglutarate, NAD(P)H + H+, and ammonia to form glutamate and NAD(P)+ (Fang et al. 2002). Mature GLUD1 protein lacks the 53 aminoterminal residues of the nascent protein (Julliard and Smith 1979), which function as a mitochondrial import signal. The active form of the enzyme is a hexamer, allosterically activated by ADP and inhibited by GTP (Fang et al. 2002; Smith et al. 2002).
R-HSA-70592 (Reactome) Cytosolic aspartate aminotransferase (glutamate oxaloacetate transaminase 1 - GOT1) catalyzes the reversible reaction of aspartate and 2-oxoglutarate (alpha-ketoglutarate) to form oxaloacetate and glutamate (Doyle et al. 1990). Unpublished crystallographic data (PBD 3IIO) suggest the enzyme is a homodimer).
R-HSA-70596 (Reactome) Mitochondrial glutamate oxaloacetate transaminase 2 (aspartate aminotransferase 2 - GOT2) catalyzes the reversible reaction of aspartate and 2-oxoglutarate (alpha-ketoglutarate) to form oxaloacetate and glutamate (Martini et al. 1985). The active form of the enzyme is inferred to be a dimer with one molecule of pyridoxal phosphate associated with each monomer.
R-HSA-70599 (Reactome) Cytosolic asparagine synthase (ASNS) catalyzes the reaction of aspartate, glutamine, and ATP to form asparagine, glutamate, AMP, and pyrophosphate. Studies of the recombinant protein expressed in E. coli suggest that the active form of the enzyme is a dimer (Van Heeke and Schuster 1989).
R-HSA-70600 (Reactome) Mitochondrial glutamate dehydrogenase 1 (GLUD1) catalyzes the reversible reaction of glutamate and NAD(P)+ to form 2-oxoglutarate, NAD(P)H + H+, and ammonia (Fang et al. 2002). Mature GLUD1 protein lacks the 53 aminoterminal residues of the nascent protein (Julliard and Smith 1979), which function as a mitochondrial import signal. The active form of the enzyme is a hexamer, allosterically activated by ADP and inhibited by GTP (Fang et al. 2002; Smith et al. 2002).
R-HSA-70606 (Reactome) Cytosolic glutamine synthetase (glutamate-ammonia ligase - GLUL) catalyzes the reaction of glutamate, ammonia, and ATP to form glutamine, ADP, and orthophosphate. The enzyme is a decamer (Krajewski et al. 2008). Mutations in the gene encoding GLUL cause glutamine deficiency in vivo (Haberle et al. 2005).
R-HSA-70609 (Reactome) Mitochondrial glutaminase (GLS) catalyzes the hydrolysis of glutamine to yield glutamate and ammonia. Two GLS enzymes have been identified, one abundantly expressed in the liver (GLS - Elgadi et al. 1999) and one abundantly expressed in kidney (GLS2 - Gomez-Fabre et al. 2000). Their biochemical properties are similar. The enzymes are inferred to function as dimers based on unpublished crystallographic data for GLS (PDB 3CZD) and studies of glutaminase enzyme purified from Ehrlich Ascites cells (Quesada et al. 1988).
R-HSA-70613 (Reactome) Mitochondrial aspartate aminotransferase catalyzes the reversible reaction of oxaloacetate and glutamate to form aspartate and 2-oxoglutarate (alpha-ketoglutarate) (Martini et al. 1985). The active form of the enzyme is inferred to be a dimer with one molecule of pyridoxal phosphate associated with each monomer.
R-HSA-70654 (Reactome) Mitochondrial ornithine aminotransferase (OAT) catalyzes the reversible reaction of ornithine and alpha-ketoglutarate to form glutamate semialdehyde and glutamate (Ohura et al. 1982). The active enzyme is a hexamer (Shen et al. 1998). Inherited OAT deficiency leads to ornithine accumulation in vivo and gyrate atrophy of the choroid and retina (Brody et al. 1992; Valle and Simell 2001).
R-HSA-70655 (Reactome) The interconversion of glutamate 5-semialdehyde (L-GluSS) and (S)-1-pyrroline-5-carboxylate (1PYR-5COOH) is a spontaneous reaction (Scriver et al. 2001).
R-HSA-70664 (Reactome) Pyrroline-5-carboxylate reductase 1 (PYCR1) catalyzes the reaction of (S)-1-pyrroline-5-carboxylate with NADH + H+ to form proline and NAD+ (De Ingeniis et al. 2012). The active enzyme is a homodecamer (Meng et al. 2006). Subcellular fractionation (De Ingeniis et al. 2012) and co-localization studies (Reversade et al. 2009) indicate that PYCR1 is mitochondrial. Its deficiency is associated with cutis laxa (Reversade et al. 2009).
R-HSA-70666 (Reactome) Mitochondrial ornithine aminotransferase (OAT) catalyzes the reversible reaction of glutamate semialdehyde and glutamate to form ornithine and alpha-ketoglutarate (Ohura et al. 1982). The active enzyme is a hexamer (Shen et al. 1998). Inherited OAT deficiency leads to ornithine accumulation in vivo and gyrate atrophy of the choroid and retina (Brody et al. 1992; Vallee and Simell 2001).
R-HSA-893616 (Reactome) CCBL1 (KAT 1) catalyzes the reaction of glutamine and pyruvate to form 2-oxoglutaramate and alanine. The active form of CCBL1 is a homodimer with one molecule of pyridoxal phosphate bound to each monomer (Baran et al. 1994; Han et al. 2009; Rossi et al. 2004). The enzyme's cytosolic localization is inferred from that of recombinant protein overexpressed in transfected cells (Perry et al. 1995).
R-HSA-8942575 (Reactome) N-Acetylaspartylglutamate (NAAG) is found at high concentrations in the vertebrate nervous system. It is an agonist of group II metabotropic glutamate receptors. A number of other functions have been proposed for NAAG, including a role as a non-excitotoxic transport form of glutamate and a molecular water pump (Lodder-Gadaczek et al. 2011, Neale et al. 2011). NAAG is synthesized by N-acetylaspartylglutamate synthase A (RIMKLA, NAAG synthetase A) and Beta-citrylglutamate synthase B (RIMKLB, NAAG synthetase B), which more efficiently catalyzes the synthesis of beta-citryl-L-glutamate (Collard et al. 2010, Lodder-Gadaczek et al. 2011).
R-HSA-8954468 (Reactome) N-acetylaspartate (NAA) is a highly abundant brain metabolite which delivers the acetate moiety for synthesis of acetyl-CoA, further utilised for fatty acid generation. In the mitochondrial matrix of neuronal cells, N-acetylaspartate synthetase (NAT8L) catalyses the formation of NAA from acetyl-CoA (Ac-CoA) and L-aspartatic acid (L-Asp) (Wiame et al. 2009, Pessentheiner et al. 2013, Prokesch et al. 2016).
R-HSA-8954513 (Reactome) Cytosolic acetyl-CoA (Ac-CoA) is used for lipid synthesis in adipocytes. N-acetylaspartate (NAA) is a source of Ac-CoA when catabolised in the cytosol. As no known specific NAA transporters have yet been identified, NAA translocates from the mitochondrial matrix to the cytosol by an unknown mechanism (Prokesch et al. 2016).
RIMKLA, RIMKLBmim-catalysisR-HSA-8942575 (Reactome)

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