Methylated Phenylarsenical Metabolites Discovered in Chicken Liver.
Methylated Phenylarsenical Metabolites Discovered in Chicken Liver.
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在鸡肝中发现甲基化苯胂代谢物
DOI：
10.1002/anie.201700736
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发表时间：
2017-06-06
期刊：
影响因子：
--
通讯作者：
Le XC
中科院分区：
文献类型：
--
作者：
Peng H;Hu B;Liu Q;Li J;Li XF;Zhang H;Le XC
我们报告了在喂食3-硝基-4-羟基苯胂酸（ROX）的鸡的肝脏中发现了三种毒理学相关的甲基化苯胂代谢物，ROX是一种仍在多个国家使用的家禽生产饲料添加剂。在这些鸡肝中鉴定出甲基-3-硝基-4-羟基苯胂酸（甲基-ROX）、甲基-3-氨基-4-羟基苯胂酸（甲基-3-AHPAA）和甲基-3-乙酰氨基-4-羟基苯胂酸（或甲基-N-乙酰基-ROX，甲基-N-AHPAA），即使在5天的清除期后，甲基-ROX的浓度仍高达90 μg kg-1。 这些新发现的甲基化代谢物的形成涉及三价苯胂酸底物，S-腺苷甲硫氨酸和砷（+3氧化态）甲基转移酶As 3 MT的反应表明，这些化合物是通过在酶促过程中将甲基添加到三价苯胂底物中形成的。三价苯砷化合物的IC_（50）值比五价苯砷化合物低300 ~ 30000倍。
We report the discovery of three toxicologically relevant methylated phenylarsenical metabolites in the liver of chickens fed 3‐nitro‐4‐hydroxyphenylarsonic acid (ROX), a feed additive in poultry production that is still in use in several countries. Methyl‐3‐nitro‐4‐hydroxyphenylarsonic acid (methyl‐ROX), methyl‐3‐amino‐4‐hydroxyphenylarsonic acid (methyl‐3‐AHPAA), and methyl‐3‐acetamido‐4‐hydroxyphenylarsonic acid (or methyl‐N‐acetyl‐ROX, methyl‐N‐AHPAA) were identified in such chicken livers, and the concentration of methyl‐ROX was as high as 90 μg kg−1, even after a five‐day clearance period. The formation of these newly discovered methylated metabolites from reactions involving trivalent phenylarsonous acid substrates, S‐adenosylmethionine, and the arsenic (+3 oxidation state) methyltransferase enzyme As3MT suggests that these compounds are formed by addition of a methyl group to a trivalent phenylarsenical substrate in an enzymatic process. The IC50 values of the trivalent phenylarsenical compounds were 300–30 000 times lower than those of the pentavalent phenylarsenicals.
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影响因子：
4.1
作者：
Drobna, Zuzana;Naranmandura, Hua;Kubachka, Kevin M.;Edwards, Brenda C.;Herbin-Davis, Karen;Styblo, Miroslav;Chris Le, X.;Creed, John T.;Maeda, Noboyu;Hughes, Michael F.;Thomas, David J.
通讯作者：
Thomas, David J.
影响因子：
6.1
作者：
Conklin, Sean D.;Shockey, Nohora;Carson, Mary C.
通讯作者：
Carson, Mary C.
影响因子：
16.6
作者：
Hansen, HR;Pickford, R;Feldmann, J
通讯作者：
Feldmann, J
影响因子：
4.8
作者：
Lin, S;Shi, Q;Thomas, DJ
通讯作者：
Thomas, DJ
影响因子：
10.4
作者：
Liu Q;Peng H;Lu X;Zuidhof MJ;Li XF;Le XC
通讯作者：
Le XC