The Meisenheimer complex of glutathione and trinitrobenzene. A potent inhibitor of the glutathione S-transferase from Galleria mellonella

Abstract

1. The Meisenheimer complex formed between reduced glutathione and 1,3,5-trinitrobenzene is characterised by an extinction coefficient at 470 nm of 20400 and by an association constant at pH 9.18 of 42 l.mol-1. 2. Trinitrobenzene is a moderately good inhibitor of the glutathione S-transferase from larvae of the moth Galleria mellonella. It acts by competition with the electrophilic substrate. At pH 7.4, it has a Ki value of 10 microM. Its mode of inhibition with respect to GSH appears to be non-competitive. 3. At pH values below 9.0, the Meisenheimer complex does not appear to be formed in sufficient quantity to give significant inhibition of the enzyme. At pH 9.0 and at GSH concentrations greater than 1 mM, the inhibition of the enzyme became markedly non-hyperbolic. This was attributed to the inhibitory action of the Meisenheimer complex. The complex appears to act also by competition with the electrophilic substrate and its Ki is calculated to be 1.7 X 10(-7) M.