Mechanism of thyroid peroxidase inhibition by ethylenethiourea.
Ethylenethiourea (ETU) is a thyroid carcinogen present in foods formed by degradation and metabolism of ethylenebis[dithiocarbamate] fungicides. ETU inhibits thyroid peroxidase (TPX), the enzyme that catalyzes synthesis of thyroid hormones. Inhibition of TPX-catalyzed reactions by ETU occurs only in the presence of iodide ion with concomitant oxidative metabolism to imidazoline and bisulfite ion. Inhibition ceases upon consumption of ETU with no loss of enzymatic activity and negligible covalent binding of ETU to TPX. TPX inhibition by ETU is unlike that for derivatives of imidazoline-2-thione, which cause suicide inactivation via covalent binding to the prosthetic heme group. These results demonstrate a metabolic route for detoxication of ETU in the thyroid and suggest that low-level or intermittent exposure to ETU would have minimal effects on thyroid hormone production.
Doerge
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DR
Department of Agricultural Biochemistry, University of Hawaii, Honolulu 96822.
Takazawa
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RS
D002250:Carbon Radioisotopes; D002851:Chromatography, High Pressure Liquid; D005031:Ethylenethiourea / Q000633:toxicity*; D006861:Hydrogen Peroxide / Q000378:metabolism; D007453:Iodide Peroxidase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D007455:Iodine / Q000378:metabolism; D010084:Oxidation-Reduction
D002250:Carbon Radioisotopes; D005031:Ethylenethiourea; D007455:Iodine; D006861:Hydrogen Peroxide; D007453:Iodide Peroxidase