Glutathione: an endogenous substrate for thiopurine methyltransferase?
An investigation was initiated to determine if glutathione is an endogenous substrate for thiopurine methyltransferase. Glutathione, as well as S-methylglutathione, were each capable of inhibiting the enzyme in a concentration-dependent manner, which suggested competitive and product inhibition, respectively. However, radiochromatography revealed that S-methylation of glutathione is not a catalytic activity of this sulfhydryl transmethylase. Subsequent experiments indicated that the inhibitory effects of both glutathione and S-methylglutathione on thiopurine methyltransferase may be due to their acidic natures, changing the reaction mixture pH away from the optimal range for the enzyme.
D000818:Animals; D002845:Chromatography / Q000379:methods; D005978:Glutathione / Q000031:analogs & derivatives / Q000378:metabolism* / Q000494:pharmacology; D006863:Hydrogen-Ion Concentration; D066298:In Vitro Techniques; D007668:Kidney / Q000201:enzymology*; D008297:Male; D008780:Methyltransferases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D010710:Phosphates / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains
D010710:Phosphates; D008780:Methyltransferases; C022745:thiopurine methyltransferase; D005978:Glutathione; C017514:S-methyl glutathione