Purine metabolism and related disorders (WP4224)

Homo sapiens

Open in new tab Open in NDEx
Download PNG Download SVG Download JSON Download GPML Learn more about Downloads
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 [https://www.wikipathways.org/instance/WP4792 here]. Proteins on this pathway have targeted assays available via the [https://assays.cancer.gov/available_assays?wp_id=WP4224 CPTAC Assay Portal]

Authors

Roel Hacking , Egon Willighagen , Denise Slenter , Martina Summer-Kutmon , Daniela Digles , Irene Hemel , Josien Landman , Kristina Hanspers , Finterly Hu , Friederike Ehrhart , and Eric Weitz

Activity

last edited

Discuss this pathway

Check for ongoing discussions or start your own.

Cited In

Are you planning to include this pathway in your next publication? See How to Cite and add a link here to your paper once it's online.

Organisms

Homo sapiens

Communities

Inherited Metabolic Disorders (IMD) Pathways Rare Diseases

Annotations

Pathway Ontology

purine nucleoside phosphorylase deficiency pathway inborn error of purine-pyrimidine metabolism pathway disease pathway xanthinuria type II pathway purine metabolic pathway adenosine monophosphate deaminase deficiency pathway Lesch-Nyhan syndrome pathway

Disease Ontology

adenylosuccinase lyase deficiency mitochondrial DNA depletion syndrome 3 Lesch-Nyhan syndrome adenosine deaminase deficiency adenine phosphoribosyltransferase deficiency

Participants
Query Drugst.One

Label Type Compact URI Comment
Moco Metabolite chebi:82685 molybdenum, cofactor for XDH and ADO enzymes
PRPP Metabolite chebi:17111
ATP Metabolite chebi:30616
XMP Metabolite chebi:57464
Moco Metabolite chebi:82685 molybdenum, cofactor for XDH and ADO enzymes
Methionine Metabolite chebi:57844
SAICARP Metabolite chebi:58443
Mg2+ Metabolite wikidata:Q26987404 Metal Ion
AICA-riboside Metabolite chebi:28498
6-oxopyrimidine (M1) Metabolite inchikey:ORGWVAZZJZJVPV-UHFFFAOYSA-N 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]
5-PRA Metabolite chebi:58681 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)
Type your comment here
AMP Metabolite chebi:456215
Xanthosine Metabolite chebi:18107
2'-Deoxyadenosine Metabolite chebi:17256
Inosine Metabolite chebi:17596
GDP Metabolite chebi:58189
Ribose-5-P Metabolite chebi:52742
6-methylthiopurine Metabolite chebi:28279
SAICA-riboside Metabolite chebi:18319
dGDP Metabolite chebi:58595
Succinyladenosine Metabolite chebi:71169
dATP Metabolite chebi:61404
ATP Metabolite wikidata:Q80863 Co-enzyme
AICARP Metabolite chebi:58475
2,8-Dihydroxyadenine Metabolite wikidata:Q4596812
dADP Metabolite chebi:57667
Adenosine Metabolite chebi:16335
dAMP Metabolite chebi:58245
Gln Metabolite wikidata:Q181619 Substrate
ITP Metabolite chebi:61402 is a nucleoside triphosphate(4−)
Hypoxanthine Metabolite chebi:17368
Guanosine Metabolite chebi:16750
auglurant Metabolite inchikey:RBAHIIPVJVMACF-UHFFFAOYSA-N VU0424238 (VU238, auglurant) aka N-(5-fluoropyridin-2-yl)-6-methyl-4-(pyrimidin-5-yloxy)picolinamide
SAM Metabolite chebi:59789 aka S-adenosyl-L-methionine
S-AMP Metabolite chebi:57567 succinyladenosine monophosphate
H2O Metabolite chebi:15377 Inorganic molecules
Xanthine Metabolite chebi:17712
ADP Metabolite chebi:456216
GTP Metabolite chebi:37565
dGTP Metabolite chebi:16497
Mercaptopurine Metabolite chebi:50667
Urate Metabolite chebi:17775
Moco (inactive) Metabolite chebi:171302 '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)
Adenine Metabolite chebi:16708
Guanine Metabolite chebi:16235
dGMP Metabolite chebi:57673
FAICARP Metabolite chebi:58467
2-Deoxyguanosine Metabolite chebi:17172
GMP Metabolite chebi:58115
2'-deoxyinosine Metabolite chebi:28997
IMP Metabolite chebi:58053
PRPP Metabolite chebi:58017
GAR Metabolite chebi:58457 ChEBI identifier will be replaced and updated by RHEA end of July
FGAR Metabolite chebi:58426
FGAM Metabolite chebi:58478
AIR Metabolite chebi:137981
CAIR Metabolite chebi:77657
AICARP Metabolite chebi:58475
SACAIR Metabolite chebi:58443
ADP Metabolite wikidata:Q185253 Co-enzyme
ATP Metabolite wikidata:Q80863 Co-enzyme
ADP Metabolite wikidata:Q185253 Co-enzyme
ATP Metabolite wikidata:Q80863 Co-enzyme
ADP Metabolite wikidata:Q185253 Co-enzyme
ATP Metabolite wikidata:Q80863 Co-enzyme
ADP Metabolite wikidata:Q185253 Co-enzyme
ATP Metabolite wikidata:Q80863 Co-enzyme
ADP Metabolite wikidata:Q185253 Co-enzyme
Glu Metabolite chebi:16015 Substrate
P(i) Metabolite wikidata:Q177811 Inorganic molecules
Mg2+ Metabolite wikidata:Q26987404 Metal Ion
P(i) Metabolite wikidata:Q177811 Inorganic molecules
Gln Metabolite wikidata:Q181619 Substrate
N(10)-formyl-THF Metabolite wikidata:Q27098160 Co-enzyme
THF Metabolite wikidata:Q168453 Co-enzyme
Gln Metabolite wikidata:Q181619 Substrate
H2O Metabolite chebi:15377 Inorganic molecules
Glu Metabolite chebi:16015 Substrate
P(i) Metabolite wikidata:Q177811 Inorganic molecules
Mg2+ Metabolite wikidata:Q26987404 Metal Ion
P(i) Metabolite wikidata:Q177811 Inorganic molecules
Mg2+ Metabolite wikidata:Q26987404 Metal Ion
HCO3 - Metabolite wikidata:Q409202 Inorganic molecules
P(i) Metabolite wikidata:Q177811 Inorganic molecules
Mg2+ Metabolite wikidata:Q26987404 Metal Ion
P(i) Metabolite wikidata:Q177811 Inorganic molecules
Asp Metabolite wikidata:Q178450 Substrate
Mg2+ Metabolite wikidata:Q26987404 Metal Ion
Fumarate Metabolite wikidata:Q139857 Substrate
P(i) Metabolite wikidata:Q177811 Inorganic molecules
Moco (active) Metabolite chebi:82685 '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)
MOCOS Protein uniprot:Q96EN8
AO Protein uniprot:Q06278 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]
APRT Protein uniprot:P07741
RRM2B Protein uniprot:Q7LG56
ATIC Protein uniprot:P31939
ADA Protein uniprot:P00813 aka Adenosine deaminase
ADSL Protein uniprot:P30566
GRM5 Protein uniprot:P41594 Metabotropic glutamate receptor 5
MAT2A Protein uniprot:P31153
PRPS1 Protein uniprot:P60891
ADSS Protein uniprot:P30520 Adenylosuccinate synthetase isozyme 2
ADSL Protein uniprot:P30566
PRPPs Protein eccode:2.7.6.1
IMPDH1 Protein uniprot:P20839
HPRT1 Protein uniprot:P00492
DGUOK Protein uniprot:Q16854
AMPD1 Protein uniprot:P23109
PNP Protein uniprot:P00491
ITPA Protein uniprot:Q9BY32
RR Protein eccode:1.17.4.1 ribonucleotide reductase
PPAT Protein uniprot:Q06203
TPMT Protein uniprot:P51580
PNP Protein uniprot:P00491
PNP Protein uniprot:P00491
XO Protein uniprot:P47989 AKA XDH
PNP Protein uniprot:P00491
RR Protein eccode:1.17.4.1
ATIC Protein uniprot:P31939
ADA Protein uniprot:P00813
PNP Protein uniprot:P00491
HPRT1 Protein uniprot:P00492
GART(E1) Protein uniprot:P22102
GART(E2) Protein uniprot:P22102
PFAS Protein uniprot:O15067
PAICS(E1) Protein uniprot:P22234
GART(E3) Protein uniprot:P22102
PAICS(E2) Protein uniprot:P22234
ADSL Protein uniprot:P30566
XO Protein uniprot:P47989 aka Xanthine oxidase; '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]
XO Protein uniprot:P47989 AKA XDH
PNP Protein uniprot:P00491

References

  1. Combined Immune Deficiencies. Su HC, Lenardo MJ. In: Stiehm’s Immune Deficiencies [Internet]. Elsevier; 2014. p. 143–69. Available from: http://dx.doi.org/10.1016/B978-0-12-405546-9.00005-4 DOI Scholia
  2. The molybdenum cofactor. Mendel RR. J Biol Chem. 2013 May 10;288(19):13165–72. PubMed Europe PMC Scholia
  3. Species-Specific Involvement of Aldehyde Oxidase and Xanthine Oxidase in the Metabolism of the Pyrimidine-Containing mGlu5-Negative Allosteric Modulator VU0424238 (Auglurant). Crouch RD, Blobaum AL, Felts AS, Conn PJ, Lindsley CW. Drug Metab Dispos. 2017 Dec;45(12):1245–59. PubMed Europe PMC Scholia
  4. Pubmed: 9783642403361