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外源化学物对 AMP 脱氨酶的体外抑制作用 一种用于评估合成硝基麝香和多环麝香、咪唑鎓离子液体以及 N-葡糖苷基铵盐风险的潜在分子方法

AMP deaminase in vitro inhibition by xenobiotics A potential molecular method for risk assessment of synthetic nitro- and polycyclic musks, imidazolium ionic liquids and N-glucopyranosyl ammonium salts.

机构信息

Intercollegiate Faculty of Biotechnology, Medical University of Gdańsk and University of Gdańsk, PL 80-211 Gdańsk, ul. Debinki 1, Poland.

出版信息

Environ Toxicol Pharmacol. 2005 Feb;19(2):291-6. doi: 10.1016/j.etap.2004.08.005.

Abstract

The usefulness of in vitro AMP deaminase inhibition was examined as a potential molecular method in risk assessment of xenobiotics. The enzyme participates in the principal purine nucleotide interconversion and degradation pathways, and its absence caused perturbations in the cellular ATP pool. The compounds selected were synthetic musks with a known negative environmental impact and the toxicologically unknown ionic liquids and N-glucopyranosyl ammonium bromides, which have recently attracted much interest from the chemical and related industries. All the compounds tested demonstrated a dose-dependent inhibition of AMP deaminase activity. IC(50) ranged from 0.3μM for polycyclic musks to 500μM for N-glucopyranosyl trimethylammonium bromide. Analysis of Dixon plots showed the inhibition type for all the compounds to be noncompetitive. The results support the choice of such an assay for the prospective risk assessment of these compounds.

摘要

体外 AMP 脱氨酶抑制作用的有用性作为一种潜在的分子方法,在评估外源性化学物质的风险中进行了研究。该酶参与嘌呤核苷酸的主要转化和降解途径,其缺失会导致细胞内 ATP 池的紊乱。选择的化合物是具有已知负环境影响的合成麝香,以及毒理学上未知的离子液体和 N-葡萄糖基三甲基氯化铵,这些化合物最近引起了化学和相关行业的极大兴趣。所有测试的化合物均表现出对 AMP 脱氨酶活性的剂量依赖性抑制。IC50 范围从多环麝香的 0.3μM 到 N-葡萄糖基三甲基铵溴化物的 500μM。Dixon 图分析表明,所有化合物的抑制类型均为非竞争性。这些结果支持选择这种测定方法来对这些化合物进行预期的风险评估。

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