Wan Yi and Hu Jianying’s Group discovers a Widespread Metabolic Pathway within Phenolic Xenobiotics

JUN . 08 2017
Peking University, May 29, 2017: Organisms are always exposed to various xenobiotics in the environment. It is common for organisms to detoxify foreign compounds by transforming them into metabolic products with low toxicity and strong water solubility so that they can be easily excreted. A lot of researches on the metabolic pathway of xenobiotics in the environment have been done in the past. It is generally acknowledged that the xenobiotics will be introduced with, or removed from functional groups first to increase polarity, and then combined with endogenous compounds by covalent bonds. After this process, the chemical will be water-soluble and easier to excrete.
Phenolic chemicals are not only products generated by aromatic substances, such as persistent organic pollutants (POPs), but also important components of endocrine disrupting substances (EDCs), such as nonylphenol, bisphenol A, and pharmaceutical and personal care products (PPCPs) including triclosan (TCS). This kind of substance is believed to be combined with glucuronic acid or sulfonic acid after a two-phase metabolic pathway and excreted from the body. However, environmental toxicology experiments suggest that its toxicity effect is more likely to be a one-phase process. The intrinsic mechanism of the contradictory phenomenon remains unclear.
Researcher Wan Yi from College of Urban and Environmental Sciences, Peking University, and his co-workers carried out research on the environmental phenolic pollutant triclosan (TCS). Through nontargeted screening, mass spectrometry and chemical synthesis, they found that TCS would generate a more fat-soluble ether metabolite (TCS-O-TCS) through a one-phase pathway. The new metabolite was found in vitro metabolism of weever, quails, and human microsomes, and in vivo metabolism of mice. Moreover, it was also detected in the urine of general population with high frequency. Due to the high fat-solubility of the metabolite, its binding activity with CAR receptor is 7.2 times of its generator, thus becoming a potential contribution of TCS to promote cancer activity. With further study, researchers discovered that the metabolic pathway is widely spread among aromatic substances and phenolic xenobiotics. Besides, reactions between different phenols are also possible, producing a series of unknown metabolites. The new pathway provides a new mechanism for cross-talk reaction of different xenobiotics in metabolic process.
The discovery was reported in Proceedings of the National Academy of Sciences USA, with Researcher Wan Yi and Professor Hu Jianying from College of Urban and Environmental Sciences as co- authors.
For more Information: Discovery of a widespread metabolic pathway within and among phenolic xenobiotics
Written by: Zhou Yijing
Edited by: Wang Yuqing/ Gan Zhonghao