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] c52 molybdenum, cofactor for XDH and ADO enzymes molybdenum, cofactor for XDH and ADO enzymes 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] Metal Ion 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] e03 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 aka Adenosine deaminase Metabotropic glutamate receptor 5 Co-enzyme Substrate is a nucleoside triphosphate(4−) Adenylosuccinate synthetase isozyme 2 VU0424238 (VU238, auglurant) aka N-(5-fluoropyridin-2-yl)-6-methyl-4-(pyrimidin-5-yloxy)picolinamide e03 aka S-adenosyl-L-methionine succinyladenosine monophosphate Inorganic molecules "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) ribonucleotide reductase AKA XDH ChEBI identifier will be replaced and updated by RHEA end of July Co-enzyme Co-enzyme Co-enzyme Co-enzyme Co-enzyme Co-enzyme Co-enzyme Co-enzyme Co-enzyme Substrate Inorganic molecules Metal Ion Inorganic molecules Substrate Co-enzyme Co-enzyme Substrate Inorganic molecules Substrate Inorganic molecules Metal Ion Inorganic molecules Metal Ion Inorganic molecules Inorganic molecules Metal Ion Inorganic molecules Substrate Metal Ion Substrate 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] Inorganic molecules AKA XDH "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) negative allosteric modulator e03 Oxidation e03 d0e bc8 Activation of receptor by L-Glu This reaction will be updated by Rhea end of July DISEASE AKA X-linked Charcot-Marie-Tooth disease-5 DISEASE DISEASE DISEASE DISEASE DISEASE DISEASE DISEASE DISEASE DISEASE aka Hypoxanthine-guanine phosphoribosyl-transferase deciciency DISEASE DISEASE aka Myoadenylate deaminase DISEASE DISEASE DISEASE DISEASE DISEASE "Mutations in MOCOS cause a deficiency of xanthine oxidase and aldehyde oxidase, named xanthinuria type II" DISEASE DISEASE DISEASE Adapted from: https://en.wikipedia.org/wiki/Purine_metabolism 9783642403361 PubMed 'Physician's Guide to the Diagnosis, Treatment, and Follow-Up of Inherited Metabolic Diseases, Chapter 41 ISBN 978-3-642-40337-8, 2014 Blau, N. Duran, M. Gibson, K.M. Dionisi-Vici, C. purine nucleoside phosphorylase deficiency pathway PW:0001777 Pathway Ontology inborn error purine-pyrimidine metabolism disease pathway PW:0001776 Pathway Ontology disease pathway PW:0000013 Pathway Ontology 28939686 PubMed 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 Crouch RD Blobaum AL Felts AS Conn PJ Lindsley CW adenylosuccinase lyase deficiency DOID:0050762 Disease mitochondrial DNA depletion syndrome 3 DOID:0080121 Disease xanthinuria disease pathway, type II PW:0001592 Pathway Ontology purine metabolic pathway PW:0000031 Pathway Ontology 10.1016/B978-0-12-405546-9.00005-4 DOI Chapter 5 Combined Immune Deficiencies https://doi.org/10.1016/B978-0-12-405546-9.00005-4 2014 Su, H Lenardo, M. Lesch-Nyhan syndrome DOID:1919 Disease adenosine deaminase deficiency DOID:5810 Disease adenine phosphoribosyltransferase deficiency DOID:0060350 Disease adenosine monophosphate deaminase deficiency pathway PW:0001779 Pathway Ontology 23539623 PubMed The Molybdenum Cofactor J. Biol. Chem. 2013 R. Mendel Lesch-Nyhan syndrome pathway PW:0001879 Pathway Ontology