Reaction of Thiol Compounds with Peroxidase and Hydrogen Peroxide*

Recent studies have indicated that peroxidase might function in the biological synthesis of thyroxine by the thyroid gland. Johnson and Tewkesbury (1) believed that thyroxine might be formed by the oxidative coupling of 2 molecules of diiodotyrosine. Westerfeld and Lowe (2) studied the oxidative condensation of p-cresol by hydrogen peroxide and peroxidase and suggested that peroxidase might be involved in the biological synthesis of thyroxine by a similar mechanism. Keston (3) intimated that hydrogen peroxide may be produced in living cells by the flavoprotein systems and that the hydrogen peroxide and peroxidase accelerated the iodination of protein in vitro. The observation that thiourea inhibited the staining of thyroid tissue by the peroxidase reagent, benzidine-hydrogen peroxide, led Dempsey (4) to propose that the antiperoxidase activity of thiourea might account for its goitrogenic activity. Glock (5) further observed that thiourea and thiouracil inhibited the action of peroxidase and hydrogen peroxide on pyrogallol; however, she found only insignificant amounts of true peroxidase in thyroid gland and considered, therefore, that the goitrogenic activity of thiourea was not due to its antiperoxidase activity. Franklin et al. (6,7) demonstrated that oxidative mechanisms were necessary for the incorporation of iodide into thyroxine by the thyroid gland. This iodination was prevented by thiouracil as well as by oxidative inhibitors. Thiourea has the properties of an antioxidant in the prevention of the discoloration of fruit (8) and in the prevention of peroxide formation in fats (9). The above observations suggested that the antioxidant properties of the thiol compounds might be related to their antithyroid activities. It was considered further that the antiperoxidase activities of the thiol compounds might be a measure of their antioxidant properties. Accordingly, a number of thiol compounds were tested for their antiperoxidase activities. Antiperoziduse Actiwilies-Lipmann’s method (10) was used for measuring the inhibitory effect of thiols on horseradish peroxidase. In this method the amount of red dye produced by the action of peroxidase and hydrogen