INHIBITION OF GLUTATHIONE TRANSFERASE BY S-BENZYL GLUTATHIONE ANALOGOUS TO THE CONJUGATE OF SALIGENIN CYCLIC PHOSPHATE

Glutathione (GSH) conjugation of saligenin cyclic phosphates produces S-(2-hydroxybenzyl)-glutathione which inhibits glutathione transferase (GSH-t, EC 2.5.1.18). The inhibitory effect of a series of S-(ring-substituted benzyl)glutathiones and some other GSH conjugates on GSH-t was elucidated. GSH-t activities were measured by 1-chloro-2,4-dinitrobenzene (CDNB) GSH conjugation and by a GSH-dependent demethylation of [ring-14C]fenitrothion. The latter activity was optimal with equine liver GSH-t at pH 7-11 and 42°C and with house fly abdominal GSH-t at pH 8.0 and 37°C. The inhibitory activity of the GSH conjugates against CDNB GSH conjugation was correlative (r = 0.59) with that against demethylation of fenitrothion. The highest inhibitory activity was found in S-(1-naphthylmethyl)glutathione among the series of the conjugates. Kinetic studies for the inhibition of CDNB GSH conjugation showed that S-(1-naphthylmethyl)glutathione was competitive with both GSH and CDNB, whereas some of the less active conjugates were only competitive with GSH. Inhibitor constants (Ki) for S-(1-naphthylmethyl)-, S-(2-chlorobenzyl)-, S-(2-hydroxybenzyl)-, and S-(2,4-dinitrophenyl)-GSH conjugates were 2.5, 6.3, 11.0, and 14.0 μM, respectively. © 1990.