Opposite effects of thiocyanate on tyrosine iodination and thyroid hormone synthesis.
The effect of a pseudohalide, SCN-, an anion with the same molecular size as iodide, was studied on two reactions: thyroglobulin iodination and thyroid hormone synthesis (coupling reaction) catalyzed by peroxidases. The coupling reaction was studied separately from the iodination reaction by using labelled thyroglobulin samples previously iodinated but containing little or no hormones. 1. SCN- inhibits iodide oxidation (I- leads to I2) whatever the enzyme, thyroid, lactoperoxidase or horseradish peroxidase. The amount of SCN- required to completely inhibit this reaction varies depending on the enzyme. Similarly tyrosine iodination is inhibited by SCN- with large variations, depending on the peroxidase, in the concentration of this anion required for inhibition. 2. In contrast SCN- stimulates the coupling reaction: (a) this affect is seen with the thyroid and lactoperoxidases but not with horseradish peroxidase; (b) the concentration of SCN- required for half-maximal stimulation of the coupling reaction is much lower (0.5-1 microM) than that required for the inhibition of iodide oxidation (60-80 microM); (c) ClO4(-), an anion with the same molecular size as SCN- and I-, has no effect on the coupling reaction; (d) this stimulatory effect of SCN- does not depend on a modification of the thyroglobulin molecule since it is not seen with horseradish peroxidase or in purely chemical coupling conditions. 3. The stimulatory effect of SCN- is therefore seen as resulting from the binding of this anion to a limited number of high-affinity sites present at the surface of both thyroid and lactoperoxidases. The inhibitory effect depends, in contrast, on the binding of SCN- to the substrate site with lower affinities. Since iodide also behaves both as a substrate for the iodination reaction and as a stimulatory ligand for the coupling reaction, these data provide further support in favour of the existence of an enzyme-iodide (or SCN-) complex with catalytic properties different from those of the native peroxidase.
D004305:Dose-Response Relationship, Drug; D006735:Horseradish Peroxidase / Q000037:antagonists & inhibitors; D006801:Humans; D007453:Iodide Peroxidase / Q000037:antagonists & inhibitors; D007454:Iodides / Q000494:pharmacology; D007455:Iodine / Q000378:metabolism*; D007700:Kinetics; D007784:Lactoperoxidase / Q000037:antagonists & inhibitors; D013861:Thiocyanates / Q000494:pharmacology*; D013954:Thyroglobulin / Q000378:metabolism*; D013974:Thyroxine / Q000096:biosynthesis*; D014443:Tyrosine / Q000378:metabolism
D007454:Iodides; D013861:Thiocyanates; D014443:Tyrosine; D013954:Thyroglobulin; D007455:Iodine; D006735:Horseradish Peroxidase; D007784:Lactoperoxidase; D007453:Iodide Peroxidase; D013974:Thyroxine