The inhibition by 6‐diazo‐5‐oxo‐L‐norleucine of glutamine catabolism of the cultured human lymphoblast

Abstract

The rapid catabolism of glutamine by the cultured human lymphoblast line WI-L2 can be inhibited greater than 95% by incubation of cell suspensions with 6-diazo-5-oxo-L-norleucine (DON). The inhibition persists for at least four hours after removal of DON from the cell suspension. The exposure of cells to DON inhibits over 95% of the glutaminase activity measured in lysates in the presence of either phosphate or maleate. Similarly, γ-glutamyl transpeptidase, assayed with γ-glutamyl-p-nitroanilide as substrate and glycylglycine as acceptor, is inhibited over 90%. DON-treated and control cells accumulated radioactive material from suspensions containing [¹⁴C]-L-glutamine at similar initial rates; the radioactive material accumulated by the DON-treated cells is all recoverable as glutamine while the radioactive material accumulated by untreated cells is principally recovered as glutamate.