Selective inhibition of gamma-glutamyl-cycle enzymes by substrate analogs.

Abstract

Substrate analogs were obtained that selectively inhibit the reactions of the .gamma.-glutamyl cycle or that were susceptible to only limited metabolism by the cycle. Thus, glutathione synthesis could be inhibited and analogs of glutathione could be synthesized that do not participate in transpeptidation. Specific inhibitors of sheep brain .gamma.-glutamylcyclotransferase and rat kidney 5-oxoprolinase were obtained. The findings offer new approaches to the in vivo study of the cycle and also to the design of more specifically directed analogs of inhibitors such as methionine sulfoximine and 6-diazo-5-oxonorleucine.