The de novo synthesis and salvage of nucleosides have been targetted for therapeutic advantage in the treatment of particular cancers and gout. Dihydrofolate reductase produces tetrahydrofolate, a cofactor required for synthesis of purines, pyrimidines and amino acids. GART allows formylation of phosphoribosylglycinamide, an early step in purine biosynthesis. Dihydroorotate dehydrogenase produces orotate, a key intermediate in pyrimidine synthesis. IMP dehydrogenase generates xanthosine monophosphate, an intermediate in GTP synthesis.

TYMS allows the interconversion of dUMP and dTMP, thereby acting as a crucial step in DNA synthesis. PNP allows separation of a nucleoside into the nucleobase and ribose phosphate for nucleotide salvage. XDH generates urate in the purine degradation pathway. Post-translational modifications of XDH convert the enzymatic reaction to a xanthine oxidase, allowing the interconversion of hypoxanthine and xanthine, with the production (or consumption) of reactive oxygen species.

* Key recommended reading is highlighted with an asterisk

Battelli MG, Bolognesi A, Polito L. (2014) Pathophysiology of circulating xanthine oxidoreductase: new emerging roles for a multi-tasking enzyme. Biochim Biophys Acta, 1842 (9): 1502-17. [PMID:24882753]

Cantu-Medellin N, Kelley EE. (2013) Xanthine oxidoreductase-catalyzed reduction of nitrite to nitric oxide: insights regarding where, when and how. Nitric Oxide, 34: 19-26. [PMID:23454592]

Day RO, Kamel B, Kannangara DR, Williams KM, Graham GG. (2016) Xanthine oxidoreductase and its inhibitors: relevance for gout. Clin Sci, 130 (23): 2167-2180. [PMID:27798228]

* Furuhashi M. (2020) New insights into purine metabolism in metabolic diseases: role of xanthine oxidoreductase activity. Am J Physiol Endocrinol Metab, 319 (5): E827-E834. [PMID:32893671]

Glander P, Hambach P, Liefeldt L, Budde K. (2012) Inosine 5'-monophosphate dehydrogenase activity as a biomarker in the field of transplantation. Clin Chim Acta, 413 (17-18): 1391-7. [PMID:21889500]

Munier-Lehmann H, Vidalain PO, Tangy F, Janin YL. (2013) On dihydroorotate dehydrogenases and their inhibitors and uses. J Med Chem, 56 (8): 3148-67. [PMID:23452331]

* Okafor ON, Farrington K, Gorog DA. (2017) Allopurinol as a therapeutic option in cardiovascular disease. Pharmacol Ther, 172: 139-150. [PMID:27916655]

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