Demonstration of enzymatic activity converting azathioprine to 6-mercaptopurine.
The enzymatic conversion of azathioprine to 6-mercaptopurine was detected at pH 6.5 with rat liver supernatants, although the non-enzymatic reaction predominated at pH 7.0 and 7.5. Glutathione S-transferase may catalize this conversion. Activities of the enzyme in liver with both zathioprine and 1,2-dichloro-4-nitrobenzene as substrate decreased upon carbon tetrachloride-induced hepatic injury. These results may explain an ineffectiveness of azathioprine in patients with severe hepatic damage.
D000818:Animals; D001379:Azathioprine / Q000378:metabolism*; D005982:Glutathione Transferase / Q000378:metabolism; D006863:Hydrogen-Ion Concentration; D066298:In Vitro Techniques; D008099:Liver / Q000201:enzymology*; D008297:Male; D015122:Mercaptopurine / Q000378:metabolism*; D051381:Rats
D015122:Mercaptopurine; D005982:Glutathione Transferase; D001379:Azathioprine