Zhang Ying, Ye Jing, Liu Min
School of Ecological and Environmental Science, East China Normal University, Shanghai 200241, China.
Curr Protein Pept Sci. 2017;18(1):48-56. doi: 10.2174/1389203717666160413124027.
Enantiomers of chiral compounds commonly undergo enantioselective transformation in most biologically mediated processes. As chiral persistent organic pollutants (POPs) are extensively distributed in the environment, differences between enantiomers in biotransformation should be carefully considered to obtain exact enrichment and specific health risks. This review provides an overview of in vivo biotransformation of chiral POPs currently indicated in the Stockholm Convention and their chiral metabolites.
Peer-reviewed journal articles focused on the research question were thoroughly searched. A set of inclusion and exclusion criteria were developed to identify relevant studies. We mainly compared the results from different animal models under controlled laboratory conditions to show the difference between enantiomers in terms of distinct transformation potential. Interactions with enzymes involved in enantioselective biotransformation, especially cytochrome P450 (CYP), were discussed. Further research areas regarding this issue were proposed.
Limited evidence for a few POPs has been found in 30 studies. Enantioselective biotransformation of α-hexachlorocyclohexane (α-HCH), chlordane, dichlorodiphenyltrichloroethane (DDT), heptachlor, hexabromocyclododecane (HBCD), polychlorinated biphenyls (PCBs), and toxaphene, has been investigated using laboratory mammal, fish, bird, and worm models. Tissue and excreta distributions, as well as bioaccumulation and elimination kinetics after administration of racemate and pure enantiomers, have been analyzed in these studies. Changes in enantiomeric fractions have been considered as an indicator of enantioselective biotransformation of chiral POPs in most studies. Results of different laboratory animal models revealed that chiral POP biotransformation is seriously affected by chirality. Pronounced results of species-, tissue-, gender-, and individual-dependent differences are observed in in vivo biotransformation of chiral POPs. Enantioselective biotransformation of chiral POPs is dependent on enzyme amounts and activities. However, the role of cytochrome P450 in enantioselective biotransformation has not yet been confirmed.
Currently available data on biotransformation of chiral POPs provide a preliminary understanding of the fate of chiral compounds in organisms. Further detailed studies of species-dependent biotransformation pathway and molecular mechanism in various animal models should be performed to comprehensively understand chiral POP biotransformation.
手性化合物的对映体在大多数生物介导过程中通常会发生对映选择性转化。由于手性持久性有机污染物（POPs）在环境中广泛分布，因此在生物转化过程中应仔细考虑对映体之间的差异，以获得准确的富集情况和特定的健康风险。本综述概述了《斯德哥尔摩公约》目前所指出的手性POPs及其手性代谢产物的体内生物转化情况。
全面检索专注于该研究问题的同行评审期刊文章。制定了一套纳入和排除标准以识别相关研究。我们主要比较了在受控实验室条件下不同动物模型的结果，以显示对映体在不同转化潜力方面的差异。讨论了与对映选择性生物转化所涉及的酶（尤其是细胞色素P450，即CYP）的相互作用。提出了关于该问题的进一步研究领域。
在30项研究中发现了关于少数POPs的有限证据。已使用实验室哺乳动物、鱼类、鸟类和蠕虫模型研究了α-六氯环己烷（α-HCH）、氯丹、二氯二苯三氯乙烷（DDT）、七氯、六溴环十二烷（HBCD）、多氯联苯（PCBs）和毒杀芬的对映选择性生物转化。在这些研究中分析了外消旋体和纯对映体给药后的组织和排泄物分布以及生物累积和消除动力学。在大多数研究中，对映体分数的变化被视为手性POPs对映选择性生物转化的指标。不同实验室动物模型的结果表明，手性POPs的生物转化受到手性的严重影响。在手性POPs的体内生物转化中观察到了明显的物种、组织、性别和个体依赖性差异。手性POPs的对映选择性生物转化取决于酶的数量和活性。然而，细胞色素P450在对映选择性生物转化中的作用尚未得到证实。
目前关于手性POPs生物转化的现有数据提供了对手性化合物在生物体中命运的初步了解。应在各种动物模型中进一步详细研究物种依赖性生物转化途径和分子机制，以全面了解手性POPs的生物转化。
