Human thiopurine methyltransferase: no evidence of activation by its substrates.
A HPLC assay was developed to assay baculovirus expressed human thiopurine methyltransferase activity. Using 6-mercaptopurine as substrate, the expressed thiopurine methyltransferase was found to have an apparent Km of 0.99 mM and a Vmax of 19 nmoles/mg/min. These values are in agreement with those determined using the standard radiometric assay for thiopurine methyltransferase activity. The effects of 6-thioguanine on 6-mercaptopurine metabolism were determined. 6-Thioguanine was found to be a mixed inhibitor of 6-mercaptopurine methylation.
Stupans
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I
Centre for Pharmaceutical Research, School of Pharmacy and Medical Sciences, University of South Australia, Adelaide. ieva.stupans@unisa.edu.au
Kirlich
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A
McKinnon
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RA
D000818:Animals; D000964:Antimetabolites, Antineoplastic / Q000378:metabolism*; D002851:Chromatography, High Pressure Liquid; D006801:Humans; D007313:Insecta; D007700:Kinetics; D015122:Mercaptopurine / Q000378:metabolism*; D008745:Methylation / Q000187:drug effects; D008780:Methyltransferases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D013379:Substrate Specificity; D013866:Thioguanine / Q000378:metabolism* / Q000494:pharmacology
D000964:Antimetabolites, Antineoplastic; D015122:Mercaptopurine; D008780:Methyltransferases; C022745:thiopurine methyltransferase; D013866:Thioguanine