Purine metabolism and related disorders (Homo sapiens)

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Moco13234Subunit ofExample reaction with AO and XO involved(related to exogeneous metabolism)Phosphoribosylpyrophosphate synthetase 1 defects8 steps involved(see right for details)Methionine metabolism and disordersXMPMercaptopurineGMPMethionineAdenosineRRM2BFAICARPHPRT1ATPATICH2OADSLdGTPMoco (inactive)SAM5-PRAITPA6-oxopyrimidine (M1)AOInosinePRPPPRPS1AMPD1ITP2'-DeoxyadenosineADSSXanthinedAMPATP6-methylthiopurinePNPGuanineDGUOKADPPPATMg2+AdenineauglurantHypoxanthineXanthosineAPRTADSLdGDPdGMPIMPDH1PRPPsSAICARPGTPTPMTdADPRRdATPGDPGuanosine2,8-DihydroxyadenineSAICA-ribosideSuccinyladenosineAMPMAT2AGRM5MOCO biosynthesisAICARPMOCOSRibose-5-PUrateADAGln2-DeoxyguanosineS-AMPMocoAICA-riboside332'-deoxyinosineIMPPNPPNPXOPNPRRATICADAPNPHPRT1PRPPGARFGARFGAMAIRCAIRAICARPSACAIRGART(E1)GART(E2)PFASPAICS(E1)GART(E3)PAICS(E2)ADSLADPATPADPATPADPATPADPATPADPGluP(i)Mg2+P(i)GlnN(10)-formyl-THFTHFGlnH2OGluP(i)Mg2+P(i)Mg2+HCO3 -P(i)Mg2+P(i)AspMg2+FumarateXOP(i)Phosphoribosylpyrophosphate synthetase superactivityAdenyl- succinate lyase deficiencyMitochondrial ribonucleotide reductase subunit 2 deficiencyAdenine phospho-ribosyltransferase deficiencyAdenosine deaminasedeficiencyPurine nucleoside phosphorylase deficiencyXanthinuria, Type ILesch-Nyhan SyndromeKelley-Seegmiller syndromeAdenosine deaminasedeficiencyAMP deaminase deficiencyLesch-Nyhansyndrome; LNSIMP dehydrogenasedeficiencyAICAr transformylase/IMP cyclohydrolase deficiencyPurinenucleosidephosphorylasedeficiencyDeoxyguanosine kinasedeficiencyXanthinuria, type IIPurine nucleoside phosphorylase deficiencyInosine triphosphatase deficiencyThiopurine S-methyltransferase deficiencyXOExample reaction of thiopurine metabolism(related to exogeneous metabolism)PNPMoco (active)


Description

Overview of purine metabolism and related diseases. Disorders resulting from an enzyme defect are highlighted in pink, metabolic markers are highlighted in red. Arrows indicate the directionality of chemical conversions.

On the right, the biosynthesis of IMP is depicted in more detail (adapted from: https://en.wikipedia.org/wiki/Purine_metabolism). The color scheme for this part of the pathway is as follows: enzymes(black), coenzymes(light orange), regular substrates/metabolites(blue), additional substrates(dark green), metal ions(turquoise), inorganic molecules(light purple).

This pathway was inspired by Ed. 5, Chapter 13 from the book of Blau (Ed. 4 Chapter 41) (ISBN 9783030677268). A similar version without the disorders and with biomarkers visualised with arrows can be found here.

Proteins on this pathway have targeted assays available via the CPTAC Assay Portal

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Ontology Terms

 

Bibliography

  1. Blau, N., Duran, M., Gibson, K.M., Dionisi-Vici, C.; '''Physician's Guide to the Diagnosis, Treatment, and Follow-Up of Inherited Metabolic Diseases, Chapter 41''; ISBN 978-3-642-40337-8,, 2014 PubMed Europe PMC Scholia
  2. R. Mendel; ''The Molybdenum Cofactor''; J. Biol. Chem., 2013 PubMed Europe PMC Scholia
  3. Crouch RD, Blobaum AL, Felts AS, Conn PJ, Lindsley CW; ''Species-Specific Involvement of Aldehyde Oxidase and Xanthine Oxidase in the Metabolism of the Pyrimidine-Containing mGlu5-Negative Allosteric Modulator VU0424238 (Auglurant).''; Drug Metab Dispos, 2017 PubMed Europe PMC Scholia
  4. Su, H, Lenardo, M.; ''Chapter 5 Combined Immune Deficiencies''; https://doi.org/10.1016/B978-0-12-405546-9.00005-4, 2014 DOI Scholia

History

View all...
CompareRevisionActionTimeUserComment
134289view05:40, 20 July 2024EgonwRemoved a template comment (and fixed the β character)
128217view03:40, 29 January 2024EweitzStandardize case
128216view03:35, 29 January 2024EweitzSoften disease color
126033view09:50, 29 March 2023DeSlUpdate layout righthand side
126032view09:49, 29 March 2023DeSlUpdated details for xantinuria II (XAN2) and included MOCOS enzyme
124954view08:25, 7 January 2023EgonwFixed the OMIM link patterns
123768view13:38, 12 August 2022DeSlAdded ed. 5 details
123767view13:35, 12 August 2022DeSlAdded lit ref. + inchikey for 6-oxoP (M1), converted AICARP line to graphical line.
120400view09:08, 30 November 2021Fehrhartboxed pathway node
119708view09:01, 5 August 2021DeSlVisualization change
119707view08:56, 5 August 2021DeSlconverted all http to https for OMIM URLs
119706view08:54, 5 August 2021DeSlFixed another OMIM URL
119705view08:53, 5 August 2021DeSlFixed two more OMIM URLs
119702view08:39, 5 August 2021DeSlfixed another OMIM URL (ADA)
119701view08:28, 5 August 2021DeSlUpdated OMIM URL for APRT disorder
119700view07:54, 5 August 2021DeSlAdded ID for auglurant
119283view10:48, 23 June 2021FinterlyAdded ISBN and DOI Biopax Info
111936view09:08, 11 September 2020DeSlModified description
108454view14:06, 20 December 2019DeSlOntology Term : 'disease pathway' added !
108453view14:06, 20 December 2019DeSlModified title
107302view12:23, 19 September 2019DeSlModified description
107301view12:20, 19 September 2019DeSlUpdated layout
107161view14:24, 17 September 2019MaintBotChEBI identifier normalization
106527view23:48, 5 September 2019KhanspersModified description
105796view22:47, 15 August 2019KhanspersModified description
104773view07:31, 13 June 2019JosienlandmanCorrected the identifier for AICA-riboside
104517view13:13, 29 May 2019JosienlandmanCorrected one Rhea identifier and one OMIM number
104472view12:26, 28 May 2019EgonwConverted another interaction to a graphical line.
104448view13:52, 27 May 2019JosienlandmanChanged interaction to graphicalline
104443view07:48, 27 May 2019Josienlandman
104422view10:58, 24 May 2019JosienlandmanComment for 5-PRA and GAR
104419view09:08, 24 May 2019JosienlandmanAdded enzyme ADSS and identifiers
104388view13:15, 23 May 2019JosienlandmanUnconnected line from AMP to IMP
104386view12:49, 23 May 2019JosienlandmanModified the ChEBI for 5-PRA and added a comment to this datanode.
104381view10:37, 23 May 2019JosienlandmanAdded more Rhea identifiers and modified Chebi identifiers
104374view13:01, 22 May 2019JosienlandmanAdded Rhea identifiers to reactions and changed Chebi identifiers
104030view17:42, 25 April 2019IreneHemelModified description
103969view11:03, 18 April 2019JosienlandmanAdded identifier to AICAR
103967view09:09, 18 April 2019JosienlandmanConnected Adenyl-succinate lyase deficiency to the conversion of SAICARP to AICARP
103966view08:45, 18 April 2019IreneHemelRemoved capitals in Guanine name
103964view08:18, 18 April 2019IreneHemelConnected TPMT deficiency to rest of pathway
103963view07:52, 18 April 2019IreneHemelChanged lines for 2 diseases to graphical line
103962view07:50, 18 April 2019IreneHemelChanged layout for reaction from ITP to IMP
103915view15:05, 15 April 2019IreneHemelModified description
103913view15:01, 15 April 2019IreneHemelModified description
103911view14:01, 15 April 2019JosienlandmanAdded Allopurinol, XO inhibitor, to distinguish Xanthinuria type I and type II
103857view11:38, 11 April 2019IreneHemelChanged arrows to conversions
103856view11:36, 11 April 2019IreneHemelAdded two diseases and reactions involved in these
103851view09:42, 11 April 2019DeSlChanged Uniprot Swissprot annotation to Trembl
103847view06:06, 11 April 2019IreneHemelChanged spelling error

External references

DataNodes

View all...
NameTypeDatabase referenceComment
2'-DeoxyadenosineMetaboliteCHEBI:17256 (ChEBI)
2'-deoxyinosineMetaboliteCHEBI:28997 (ChEBI)
2,8-DihydroxyadenineMetaboliteQ4596812 (Wikidata)
2-DeoxyguanosineMetaboliteCHEBI:17172 (ChEBI)
5-PRAMetaboliteCHEBI:58681 (ChEBI) ChEBI for 5-phospho-β-D-ribosylamine that is used in the conversion from 5-PRA to GAR. The ChEBI for 5-PRA in the conversion from PRPP to 5-PRA is 58089 (5-phospho-D-ribosylamine)
6-methylthiopurineMetaboliteCHEBI:28279 (ChEBI)
6-oxopyrimidine (M1)MetaboliteORGWVAZZJZJVPV-UHFFFAOYSA-N (InChIKey) Oxidize version of auglurant, N-(5-fluoropyridin-2-yl)-6-methyl-4-((6-oxo)1,6-dihydropyrimidin-5-yloxy)picolinamide, aka VU0652922; structure drawn based on Fig. 1 [PMID:28939686]
ADAProteinP00813 (Uniprot-TrEMBL)
ADPMetaboliteCHEBI:456216 (ChEBI)
ADPMetaboliteQ185253 (Wikidata) Co-enzyme
ADSLProteinP30566 (Uniprot-TrEMBL)
ADSSProteinP30520 (Uniprot-TrEMBL) Adenylosuccinate synthetase isozyme 2
AICA-ribosideMetaboliteCHEBI:28498 (ChEBI)
AICARPMetaboliteCHEBI:58475 (ChEBI)
AIRMetaboliteCHEBI:137981 (ChEBI)
AMPMetaboliteCHEBI:456215 (ChEBI)
AMPD1ProteinP23109 (Uniprot-TrEMBL)
AOProteinQ06278 (Uniprot-TrEMBL)
  • Aldehyde oxidase (AO) is a metabolizing enzyme, located in the cytosolic compartment of tissues in many organisms. AO catalyzes the oxidation of aldehydes into carboxylic acid, and in addition, catalyzes the hydrozylation of some heterocycles.[1] It can also catalyze the oxidation of both cytochrome P450 (CYP450) and monoamine oxidase (MAO) intermediate products. AO plays a very important role in the metabolization of numerous drugs.
  • "Aldehyde oxidase (AO) and xanthine oxidase (XO) belong to a family of molybdo-flavoenzymes that catalyze the oxidation of nitrogen-containing aromatic heterocycles." [PMID:28939686]
APRTProteinP07741 (Uniprot-TrEMBL)
ATICProteinP31939 (Uniprot-TrEMBL)
ATPMetaboliteCHEBI:30616 (ChEBI)
ATPMetaboliteQ80863 (Wikidata) Co-enzyme
AdenineMetaboliteCHEBI:16708 (ChEBI)
AdenosineMetaboliteCHEBI:16335 (ChEBI)
AspMetaboliteQ178450 (Wikidata) Substrate
CAIRMetaboliteCHEBI:77657 (ChEBI)
DGUOKProteinQ16854 (Uniprot-TrEMBL)
FAICARPMetaboliteCHEBI:58467 (ChEBI)
FGAMMetaboliteCHEBI:58478 (ChEBI)
FGARMetaboliteCHEBI:58426 (ChEBI)
FumarateMetaboliteQ139857 (Wikidata) Substrate
GARMetaboliteCHEBI:58457 (ChEBI) ChEBI identifier will be replaced and updated by RHEA end of July
GART(E1)ProteinP22102 (Uniprot-TrEMBL)
GART(E2)ProteinP22102 (Uniprot-TrEMBL)
GART(E3)ProteinP22102 (Uniprot-TrEMBL)
GDPMetaboliteCHEBI:58189 (ChEBI)
GMPMetaboliteCHEBI:58115 (ChEBI)
GRM5ProteinP41594 (Uniprot-TrEMBL) Metabotropic glutamate receptor 5
GTPMetaboliteCHEBI:37565 (ChEBI)
GlnMetaboliteQ181619 (Wikidata) Substrate
GluMetaboliteCHEBI:16015 (ChEBI) Substrate
GuanineMetaboliteCHEBI:16235 (ChEBI)
GuanosineMetaboliteCHEBI:16750 (ChEBI)
H2OMetaboliteCHEBI:15377 (ChEBI) Inorganic molecules
HCO3 -MetaboliteQ409202 (Wikidata) Inorganic molecules
HPRT1ProteinP00492 (Uniprot-TrEMBL)
HypoxanthineMetaboliteCHEBI:17368 (ChEBI)
IMPMetaboliteCHEBI:58053 (ChEBI)
IMPDH1ProteinP20839 (Uniprot-TrEMBL)
ITPAProteinQ9BY32 (Uniprot-TrEMBL)
ITPMetaboliteCHEBI:61402 (ChEBI) is a nucleoside triphosphate(4−)
InosineMetaboliteCHEBI:17596 (ChEBI)
MAT2AProteinP31153 (Uniprot-TrEMBL)
MOCO biosynthesisPathwayWP4507 (WikiPathways)
MOCOSProteinQ96EN8 (Uniprot-TrEMBL)
MercaptopurineMetaboliteCHEBI:50667 (ChEBI)
Methionine metabolism and disordersPathwayWP4292 (WikiPathways)
MethionineMetaboliteCHEBI:57844 (ChEBI)
Mg2+MetaboliteQ26987404 (Wikidata) Metal Ion
Moco (active)MetaboliteCHEBI:82685 (ChEBI) "In addition to the dithiolene sulfurs of the pterin moiety and two oxo groups, the molybdenum atom of Moco needs the addition of a terminal inorganic sulfur to provide enzyme activity to these enzymes (55). This final step is catalyzed by the Moco sulfurase protein (ABA3 in plants and HMCS in humans) " [PMID:23539623]. HMCS is an alternative name for MOCOS (in UniProt, https://www.uniprot.org/uniprotkb/Q96EN8/entry)
Moco (inactive)MetaboliteCHEBI:171302 (ChEBI) "In addition to the dithiolene sulfurs of the pterin moiety and two oxo groups, the molybdenum atom of Moco needs the addition of a terminal inorganic sulfur to provide enzyme activity to these enzymes (55). This final step is catalyzed by the Moco sulfurase protein (ABA3 in plants and HMCS in humans) " [PMID:23539623]. HMCS is an alternative name for MOCOS (in UniProt, https://www.uniprot.org/uniprotkb/Q96EN8/entry)
MocoMetaboliteCHEBI:82685 (ChEBI) molybdenum, cofactor for XDH and ADO enzymes
N(10)-formyl-THFMetaboliteQ27098160 (Wikidata) Co-enzyme
P(i)MetaboliteQ177811 (Wikidata) Inorganic molecules
PAICS(E1)ProteinP22234 (Uniprot-TrEMBL)
PAICS(E2)ProteinP22234 (Uniprot-TrEMBL)
PFASProteinO15067 (Uniprot-TrEMBL)
PNPProteinP00491 (Uniprot-TrEMBL)
PPATProteinQ06203 (Uniprot-TrEMBL)
PRPPMetaboliteCHEBI:17111 (ChEBI)
PRPPMetaboliteCHEBI:58017 (ChEBI)
PRPPsProtein2.7.6.1 (Enzyme Nomenclature)
PRPS1ProteinP60891 (Uniprot-TrEMBL)
RRProtein1.17.4.1 (Enzyme Nomenclature)
RRM2BProteinQ7LG56 (Uniprot-TrEMBL)
Ribose-5-PMetaboliteCHEBI:52742 (ChEBI)
S-AMPMetaboliteCHEBI:57567 (ChEBI) succinyladenosine monophosphate
SACAIRMetaboliteCHEBI:58443 (ChEBI)
SAICA-ribosideMetaboliteCHEBI:18319 (ChEBI)
SAICARPMetaboliteCHEBI:58443 (ChEBI)
SAMMetaboliteCHEBI:59789 (ChEBI) aka S-adenosyl-L-methionine
SuccinyladenosineMetaboliteCHEBI:71169 (ChEBI)
THFMetaboliteQ168453 (Wikidata) Co-enzyme
TPMTProteinP51580 (Uniprot-TrEMBL)
UrateMetaboliteCHEBI:17775 (ChEBI)
XMPMetaboliteCHEBI:57464 (ChEBI)
XOProteinP47989 (Uniprot-TrEMBL) AKA XDH
XanthineMetaboliteCHEBI:17712 (ChEBI)
XanthosineMetaboliteCHEBI:18107 (ChEBI)
auglurantMetaboliteRBAHIIPVJVMACF-UHFFFAOYSA-N (InChIKey) VU0424238 (VU238, auglurant) aka N-(5-fluoropyridin-2-yl)-6-methyl-4-(pyrimidin-5-yloxy)picolinamide
dADPMetaboliteCHEBI:57667 (ChEBI)
dAMPMetaboliteCHEBI:58245 (ChEBI)
dATPMetaboliteCHEBI:61404 (ChEBI)
dGDPMetaboliteCHEBI:58595 (ChEBI)
dGMPMetaboliteCHEBI:57673 (ChEBI)
dGTPMetaboliteCHEBI:16497 (ChEBI)

Annotated Interactions

View all...
SourceTargetTypeDatabase referenceComment
2'-DeoxyadenosineAdeninemim-conversion27743 (Rhea)
2'-deoxyinosineHypoxanthinemim-conversion27751 (Rhea)
2'-deoxyinosinemim-conversion28191 (Rhea)
2-DeoxyguanosineGuaninemim-conversion27739 (Rhea)
2-DeoxyguanosinedGMPmim-conversion19202 (Rhea)
5-PRAGARmim-conversion17454 (Rhea) This reaction will be updated by Rhea end of July
ADPATPmim-conversion30657 (Rhea)
ADPdADPmim-conversion28036 (Rhea)
AICARPFAICARPmim-conversion22193 (Rhea)
AIRCAIRmim-conversion10794 (Rhea)
AMPADPmim-conversion11462 (Rhea)
AMPAdenosinemim-conversion29376 (Rhea)
AMPIMPmim-conversion14778 (Rhea)
ATPSAMmim-conversion21081 (Rhea)
AdenineAMPmim-conversion16611 (Rhea)
AdenosineAdeninemim-conversion18670 (Rhea)
AdenosineInosinemim-conversion24409 (Rhea)
CAIRAIRmim-conversion10793 (Rhea)
CAIRSACAIRmim-conversion22629 (Rhea)
FAICARPIMPmim-conversion18447 (Rhea)
FGAMAIRmim-conversion23032 (Rhea)
FGARFGAMmim-conversion17130 (Rhea)
GARFGARmim-conversion15054 (Rhea)
GDPGTPmim-conversion29865 (Rhea)
GDPdGDPmim-conversion28032 (Rhea)
GMPGDPmim-conversion20781 (Rhea)
GMPGuanosinemim-conversion27715 (Rhea)
GuanineGMPmim-conversion25426 (Rhea)
Guaninemim-conversion14666 (Rhea)
GuanosineGuaninemim-conversion13234 (Rhea)
HypoxanthineXanthinemim-conversion24671 (Rhea)
Hypoxanthinemim-conversion17975 (Rhea)
IMPInosinemim-conversion27719 (Rhea)
IMPS-AMPmim-conversion15754 (Rhea)
IMPXMPmim-conversion11709 (Rhea)
ITPIMPmim-conversion29400 (Rhea)
InosineHypoxanthinemim-conversion16658 (Rhea)
Mercaptopurine6-methylthiopurinemim-conversion12610 (Rhea)
Methioninemim-conversion21081 (Rhea)
Moco (inactive)Moco (active)mim-conversion42637 (Rhea)
PRPP5-PRAmim-conversion14907 (Rhea)
S-AMPAMPmim-conversion16854 (Rhea)
SACAIRAICARPmim-conversion23921 (Rhea)
SACAIRCAIRmim-conversion22630 (Rhea)
SAICARPAICARPmim-conversion23921 (Rhea)
SAMmim-conversion12610 (Rhea)
XMPGMPmim-conversion18302 (Rhea)
XMPXanthosinemim-conversion28531 (Rhea)
XanthineUratemim-conversion16670 (Rhea)
XanthosineXanthinemim-conversion27639 (Rhea)
dADPdAMPmim-conversion23102 (Rhea)
dADPdATPmim-conversion27675 (Rhea)
dAMP2'-Deoxyadenosinemim-conversion29372 (Rhea)
dGDPdGMPmim-conversion12699 (Rhea)
dGDPdGTPmim-conversion27691 (Rhea)
dGMP2-Deoxyguanosinemim-conversion19203 (Rhea)
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