Doerge D R, Takazawa R S
Department of Agricultural Biochemistry, University of Hawaii, Honolulu 96822.
Chem Res Toxicol. 1990 Mar-Apr;3(2):98-101. doi: 10.1021/tx00014a003.
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.
乙撑硫脲（ETU）是一种存在于食品中的甲状腺致癌物，由乙烯双[二硫代氨基甲酸盐]类杀菌剂降解和代谢形成。ETU抑制甲状腺过氧化物酶（TPX），该酶催化甲状腺激素的合成。ETU对TPX催化反应的抑制仅在碘离子存在的情况下发生，同时伴随着氧化代谢生成咪唑啉和亚硫酸氢根离子。食用ETU后抑制作用停止，酶活性无损失，且ETU与TPX的共价结合可忽略不计。ETU对TPX的抑制作用不同于咪唑啉-2-硫酮的衍生物，后者通过与辅基血红素基团共价结合导致自杀性失活。这些结果证明了ETU在甲状腺中的解毒代谢途径，并表明低水平或间歇性接触ETU对甲状腺激素产生的影响极小。
