Inhibitors of Ovine Brain Glutamine Synthetase

The following carbobenzoxy (Cbz) derivatives of amino acids markedly inhibit ovine brain glutamine synthetase: Cbz‐DL‐phenylglycine, α‐N‐Cbz‐β‐N‐benzyl‐L‐asparagine, Cbz‐L‐phenylalanine, Cbz‐L‐tryptophan, N‐Cbz‐S‐benzyl‐L‐cysteine, and α‐ϵ‐di‐Cbz‐L‐lysine. In all cases tested, the inhibition was of a mixed type. Cbz‐derivatives of aliphatic amino acids inhibit the synthesizing reaction rather weakly. In the presence of methanol (22% v/v) or ethanol (22% v/v) the synthesizing reaction is not, or only slightly, inhibited by Cbz‐derivatives which, at the same molar concentration, are highly inhibitory in the absence of the organic solvents. When, after preincubation with methanol or ethanol, the alcohols are removed by dialysis, the original susceptibility of the enzyme to the inhibitors is restored. The inhibitors are also ineffective in the presence of dioxane (11% v/v). Cbz‐derivatives of amino acids with an additional aromatic group also strongly inhibit the γ‐glutamyl transfer activity of ovine brain preparations. There, too, the inhibition is highly diminished in the presence of organic solvents. Whereas methanol and ethanol lower both the apparent Km and the maximum velocity of the synthesizing reaction, the maximum velocity of the transfer reaction is considerably increased in the presence of these alcohols.