Abstract
Triethyltin is well known for its ability to produce cerebral oedema in vivo and inhibit oxidative phosphorylation in vitro. Previous work has shown that triethyltin binds to very few proteins which include rat brain myelin, rat haemoglobin, and rat liver mito- chondrial and supernatant fractions, with an affinity of 10[5] - 10[6] M[-1]. Rat haemoglobin has been used as a model for the binding of triethyltin to the other more complex protein fractions. In this study, triethyltin has been shown to bind to cat haemoglobin and the stoichiometry of the binding to the two haemoglobins clarified, 2. 0 moles of triethyltin per mole of haemoglobin. Diethylpyrocarbonate has been used at pH 6 as a reagent for modifying histidine residues in both cat and rat haemoglobins, and a study of the binding of triethyltin to the modified haemoglobin has shown an inequality in the two sites, with only one site being removed after exhaustive treatment. Treatment with diethylpyrocarbonate of the other proteins to which triethyltin binds, has also provided evidence suggesting more than one class of binding site of affinity 10[5] - 10[6] M[-1]. Studies of triethyltin binding to cat haemoglobin following modification of the protein with several selective chemical reagents has led to the hypothesis that triethyltin binds to two classes of site on cat haemoglobin, involving pentacoordination of the tin between two cysteine residues or a histidine and cysteine residue. In addition, triethyltin has been shown to bind to cat haemoglobin, after treatment with diethylpyrocarbonate at pH 8, to a class of sites of unknown structure. The relevance of the binding sites on cat haemoglobin to the interaction of triethyltin with other proteins has been considered. A tentative identification of the protein in rat liver supernatant which binds triethyltin has been made as the glutathione S-transferase group of enzymes. Triethyltin binding to purified glutathione S-transferase fractions has been studied, together with its inhibitory action on their enzyme activity.