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.