Syngenta, Jealott's Hill International Research Centre, Bracknell, Berkshire, RG42 6EY, UK.
Sci Rep. 2018 Sep 6;8(1):13333. doi: 10.1038/s41598-018-31215-w.
We investigated the metabolic capabilities of C. elegans using compounds whose metabolism has been well characterised in mammalian systems. We find that similar metabolites are produced in C. elegans as in mammals but that C. elegans is deficient in CYP1-like metabolism, as has been seen in other studies. We show that CYP-34A9, CYP-34A10 and CYP-36A1 are the principal enzymes responsible for the metabolism of tolbutamide in C. elegans. These are related to the mammalian enzymes that metabolise this compound but are not the closest homologs suggesting that sequence comparison alone will not predict functional conservation among cytochrome P450s. In mammals, metabolite production from amytryptiline and dextromethorphan is dependent on specific cytochrome P450s. However, in C. elegans we did not find evidence of similar specificity: the same metabolites were produced but in small amounts by numerous cytochrome P450s. We conclude that, while some aspects of cytochrome P450 mediated metabolism in C. elegans are similar to mammals, there are differences in the production of some metabolites and in the underlying genetics of metabolism.
我们使用在哺乳动物系统中代谢特征良好的化合物研究了秀丽隐杆线虫的代谢能力。我们发现，与哺乳动物相似的代谢物在秀丽隐杆线虫中产生，但秀丽隐杆线虫缺乏 CYP1 样代谢，这在其他研究中也有发现。我们表明，CYP-34A9、CYP-34A10 和 CYP-36A1 是负责秀丽隐杆线虫中甲苯磺丁脲代谢的主要酶。这些酶与代谢这种化合物的哺乳动物酶有关，但不是最接近的同源物，这表明仅序列比较不会预测细胞色素 P450 之间的功能保守性。在哺乳动物中，阿米替林和右美沙芬的代谢产物的产生依赖于特定的细胞色素 P450。然而，在秀丽隐杆线虫中，我们没有发现类似特异性的证据：相同的代谢物由许多细胞色素 P450 产生，但数量很少。我们得出结论，尽管秀丽隐杆线虫中细胞色素 P450 介导的代谢的某些方面与哺乳动物相似，但在某些代谢物的产生和代谢的潜在遗传方面存在差异。
