Reactome | XDH oxidises 6MP to 6TU

XDH oxidises 6MP to 6TU

Stable Identifier

R-HSA-9748991

Type

Reaction [transition]

Species

Homo sapiens

Compartment

cytosol

Synonyms

6MP--XDH-->6TU

ReviewStatus

5/5

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6-mercaptopurine (6MP) can be metabolized via three competing pathways; oxidation by xanthine oxidase (XDH), methylation by thiopurine methyl S-transferase (TPMT) and conversion by hypoxanthine-guanine phosphoribosyltransferase (HPRT1).

6-mercaptopurine (6MP) is subjected to high first-pass metabolism due to oxidation in intestinal cells and liver cells by xanthine oxidase (XDH) (Saksela & Raivio 1996, Yamaguchi et al. 2007, Choughule et al. 2014). This reaction produces an inactive metabolite 6-thiouric acid (6TU, via 8-OH-6MP), which is excreted in urine. Patients with low XDH expression can exhibit elevated levels of the toxic antimetabolite 6MP which might result in a higher risk of thiopurine-induced adverse effects (Ding et al. 2021).

Literature References

PubMed ID	Title	Journal	Year
8670112	Cloning and expression in vitro of human xanthine dehydrogenase/oxidase Saksela, M, Raivio, KO	Biochem J	1996
24824603	In vitro oxidative metabolism of 6-mercaptopurine in human liver: insights into the role of the molybdoflavoenzymes aldehyde oxidase, xanthine oxidase, and xanthine dehydrogenase Choughule, KV, Barnaba, C, Joswig-Jones, CA, Jones, JP	Drug Metab Dispos	2014
17301077	Human xanthine oxidase changes its substrate specificity to aldehyde oxidase type upon mutation of amino acid residues in the active site: roles of active site residues in binding and activation of purine substrate Yamaguchi, Y, Matsumura, T, Ichida, K, Okamoto, K, Nishino, T	J Biochem	2007