Reaction: NUDT15 dimer dephosphorylates 6TdGTP to 6TdGMP
- in pathway: Azathioprine ADME
Nucleotide triphosphate diphosphatase (NUDT15) is thought to catalyze the hydrolysis of nucleoside triphosphates, including the prodrug thiopurine derivatives 6-thio-dGTP and 6-thio-GTP, and stops their incorporation into DNA and RNA respectively (Kasumi et al. 1993, Carter et al. 2015, Hashiguchi et al. 2018). Polymorphisms in NUDT15 are associated with thiopurine intolerance in Asian populations (Tanaka & Saito 2021). Defective NUDT15 alleles show excessive levels of thiopurine active metabolites and toxicity (Moriyama et al. 2016).
Reaction - small molecule participants:
PPi [cytosol]
6TdGMP [cytosol]
H2O [cytosol]
6TdGTP [cytosol]
Reactome.org reaction link: R-HSA-9750555
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Reaction input - small molecules:
water
6-thiodeoxyguanosine triphosphate (4-)
Reaction output - small molecules:
diphosphate(3-)
6 thiodeoxyguanosine monophosphate (2-)
Reactome.org link: R-HSA-9750555