Thiopurine S‑methyltransferase- and indolethylamine N‑methyltransferase-mediated formation of methylated tellurium compounds from tellurite.

IF 4.8 2区医学 Q1 TOXICOLOGY

Archives of Toxicology Pub Date : 2024-10-17 DOI:10.1007/s00204-024-03890-4

Yu-Ki Tanaka, Ayuka Takata, Karin Takahashi, Yoshikazu Yamagishi, Yasunori Fukumoto, Noriyuki Suzuki, Yasumitsu Ogra

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Abstract

Tellurium (Te) is a metalloid widely used in various industries. However, its toxicological impact on humans is poorly understood. In this study, we investigated the role of two methyltransferases, thiopurine S‑methyltransferase (TPMT) and indolethylamine N‑methyltransferase (INMT), in the methylation of tellurite, an inorganic Te oxyanion. The products of the reaction of Te compounds catalyzed by recombinant human TPMT and/or INMT were analyzed by liquid chromatography hyphenated to inductively coupled plasma mass spectrometry (LC-ICP-MS) and gas chromatography mass spectrometry (GC-MS). We found that TPMT catalyzes the methylation of non-methylated Te and methanetellurol to generate dimethyltelluride. On the other hand, INMT catalyzes the methylation of methanetellurol and dimethyltelluride to produce trimethyltelluronium ion, a metabolite excreted into animal urine. We conclude that TPMT and INMT are cooperatively responsible for the detoxification of Te oxyanions through methylation to form trimethyltelluronium ions.

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硫代嘌呤 S-甲基转移酶和吲哚乙胺 N-甲基转移酶介导的亚碲酸盐甲基化碲化合物的形成。

碲（Te）是一种广泛应用于各行各业的类金属。然而，人们对其对人体的毒理影响知之甚少。在这项研究中，我们研究了两种甲基转移酶（硫嘌呤 S-甲基转移酶（TPMT）和吲哚乙胺 N-甲基转移酶（INMT））在碲（一种无机碲氧阴离子）甲基化过程中的作用。通过液相色谱-电感耦合等离子体质谱（LC-ICP-MS）和气相色谱-质谱（GC-MS）分析了重组人 TPMT 和/或 INMT 催化的 Te 化合物反应产物。我们发现，TPMT 催化非甲基化碲和甲烷四氢呋喃的甲基化，生成二甲基四氢呋喃。另一方面，INMT 催化甲烷四呋喃和二甲基碲的甲基化，生成三甲基碲离子，这种代谢物排泄到动物尿液中。我们的结论是，TPMT 和 INMT 通过甲基化形成三甲基碲离子，共同负责碲氧阴离子的解毒。

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来源期刊

Archives of Toxicology 医学-毒理学

CiteScore

11.60

自引率

4.90%

发文量

218

审稿时长

1.5 months

期刊介绍： Archives of Toxicology provides up-to-date information on the latest advances in toxicology. The journal places particular emphasis on studies relating to defined effects of chemicals and mechanisms of toxicity, including toxic activities at the molecular level, in humans and experimental animals. Coverage includes new insights into analysis and toxicokinetics and into forensic toxicology. Review articles of general interest to toxicologists are an additional important feature of the journal.