Carboxylesterases: Dual roles in lipid and pesticide metabolism.
Carboxylesterases: Dual roles in lipid and pesticide metabolism.
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DOI：
10.1584/jpestics.r10-07
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发表时间：
2010
影响因子：
2.4
通讯作者：
Herring KL
中科院分区：
文献类型：
--
作者：
Ross MK;Streit TM;Herring KL
羧酸酯酶（CES, EC 3.1.1.1）是丝氨酸水解酶超家族的成员，可水解酯、酰胺和氨基甲酸酯键。哺乳动物物种中存在几种不同的CES基因，有证据表明，在整个进化史中发生了多次基因复制事件。在人类基因组组织数据库中报道了5个CES基因，尽管CES1和CES2是两个最具特征的人类基因。对CES家族的新认识表明，这些酶在外源性和内源性化合物的代谢中具有双重作用。杀虫剂，如拟除虫菊酯，是重要的外源底物，可被CES代谢，而胆固醇酯、三酰基甘油和2-花生四烯醇甘油是已知的内源性底物，可被CES代谢。使用选择性化学抑制剂、siRNA和基因敲除模型的功能研究为CES的生理功能提供了有价值的见解，并表明CES可能是治疗糖尿病和动脉粥样硬化等疾病的新靶点。本综述将研究已知的CES生理功能，外源生物（主要是农药）和脂质与CES酶之间的相互作用，以及这些发现可能对健康和疾病产生的影响。
Carboxylesterases (CES, EC 3.1.1.1) are members of a superfamily of serine hydrolases that hydrolyze ester, amide, and carbamate bonds. Several different CES genes exist in mammalian species with evidence of multiple gene duplication events occurring throughout evolutionary history. There are five CES genes reported in the Human Genome Organization database, although CES1 and CES2 are the two best characterized human genes. An emerging picture of the CES family suggests that these enzymes have dual roles in the metabolism of xenobiotic and endobiotic compounds. Pesticides, such as the pyrethroids, are important xenobiotic substrates that are metabolized by CES, whereas cholesteryl esters, triacylglycerols, and 2-arachidonoylglycerol are examples of endobiotics known to be substrates for CES. Functional studies using selective chemical inhibitors, siRNA, and gene knockout models are providing valuable insights into the physiological functions of CES, and suggest that CES may be a novel target for the treatment of diseases such as diabetes and atherosclerosis. This review will examine the known physiological functions of CES, the interactions between xenobiotics (primarily pesticides) and lipids that occur with CES enzymes, and where possible the implications that these findings may have in terms of health and disease.