Cytochrome P-450 dependent irreversible binding of 6-thiopurine to rat liver microsomal protein in vitro and protection by glutathione.
6-Thiopurine when incubated in the presence of rat liver microsomes and reduced nicotine adenine dinucleotide phosphate (NADPH) binds to microsomal protein. Data support a mechanism involving initial metabolic activation via a cytochrome P450 mediated reaction to an intermediate which binds to protein. Glutathione protects against protein binding of the 6-thiopurine metabolite.
D000818:Animals; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D004247:DNA / Q000378:metabolism; D005978:Glutathione / Q000494:pharmacology*; D066298:In Vitro Techniques; D008297:Male; D008862:Microsomes, Liver / Q000378:metabolism*; D009249:NADP / Q000378:metabolism; D011485:Protein Binding / Q000187:drug effects; D011506:Proteins / Q000378:metabolism; D011687:Purines / Q000378:metabolism*; D012313:RNA / Q000378:metabolism; D051381:Rats
D011506:Proteins; D011687:Purines; D009249:NADP; D012313:RNA; D004247:DNA; D003577:Cytochrome P-450 Enzyme System; D005978:Glutathione