School of Pharmaceutical Science and Technology, Health Sciences Platform, Tianjin University, Tianjin, China.
Laboratoire Charles Fabry, Institut d'Optique Graduate School, CNRS, Université Paris Saclay, Palaiseau cedex, France.
Biotechnol J. 2021 Jul;16(7):e2100007. doi: 10.1002/biot.202100007. Epub 2021 May 25.
Probe substrates are an important tool for activity monitoring of human drug metabolizing enzymes such as cytochromes P450 (CYPs).
In the present study we have tested human CYPs for metabolization of five proluciferin ester substrates which had previously only been known to be hydroxylated by CYP26A1.
It was found that these substrates were converted by another 21 human CYPs, which belong to the CYP families 1 to 4, 7, and 26. Thus, 66 new pairs of enzyme and substrate were identified. Correlation analysis indicated the presence of three distinct sets of enzymes with high similarity in their activity profiles that encompass a total of 16 individual enzymes.
Some of these newly identified correlations may serve as a starting point for further study of those human CYPs whose activities are not yet satisfactorily understood.
探针底物是监测人类药物代谢酶（如细胞色素 P450（CYPs））活性的重要工具。
在本研究中，我们测试了人类 CYP 对以前仅被认为可被 CYP26A1 羟化的五种原荧光素酯底物的代谢作用。
发现这些底物可被属于 CYP 家族 1 至 4、7 和 26 的另外 21 种人类 CYP 转化。因此，鉴定出了 66 对新的酶-底物对。相关性分析表明，存在三种具有高度相似活性谱的不同酶集合，共涵盖 16 种单独的酶。
这些新发现的相关性中的一些可能成为进一步研究那些活性尚未得到充分了解的人类 CYP 的起点。
