Phase I and Phase II Xenobiotic-Metabolizing Enzymes: Structure, Function, and Regulation

Topic Information

Dear Colleagues,

Enzymes that catalyse the biotransformation of foreign compounds are generally referred to as xenobiotics‐metabolizing enzymes (XMEs). XMEs catalyse functionalization and conjugation reactions that lead to the conversion of xenobiotics to more water-soluble compounds, facilitating the excretion of xenobiotics from the cell. The biotransformation reactions of xenobiotics are classified into two sequential phases: phase I (oxidation, reduction, and hydrolysis reactions) and phase II (conjugation reactions). Phase I reactions expose or introduce a functional group (—OH, —NH₂, —SH, or —COOH), and they usually only result in a small increase in hydrophilicity. Phase II biotransformation reactions include glucuronidation, sulfation, acetylation, methylation, and conjugation with the tripeptide glutathione, which usually result in increased hydrophilicity and elimination. XMEs typically have highly plastic active sites that can accommodate a variety of substrates. It is well established that the combination of phase I and phase II XMEs and the resulting balance between metabolic activation and detoxification may be critical for the toxicity of xenobiotics. The human genome contains a large number of genes that encode XMEs. Genetic and functional variations in these genes are substantial and have complex consequences that depend, for example, on whether enzyme structure or expression is affected, or whether the metabolites produced are pharmacologically or toxicologically active. XMEs are often coordinately induced by a variety of chemical agents through the Keap1-Nrf2-ARE signalling pathway, which plays a critical role in the expression of many XMEs and acts as a sensor of oxidative stress. For this topic, we welcome reviews and/or original research papers in the field of XMEs in various organisms (humans, animals, invertebrates, plants, etc.). XMEs are key players among the many enzyme and transporter systems affecting the therapeutic or toxic effects of a xenobiotic. Structural/functional information about the XME-mediated biotransformation of xenobiotics is just one piece of a bigger puzzle when studying toxic outcomes in humans or environmental species. Researchers are cordially invited to submit studies relevant to these topics.

Prof. Dr. Nikolaos Labrou
Prof. Dr. Anastassios C. Papageorgiou
Topic Editors

Keywords

Participating Journals

Journal Name	Impact Factor	CiteScore	Launched Year	First Decision (median)	APC
BioChem biochem	-	-	2021	54 Days	CHF 1000	Submit
Biomolecules biomolecules	4.8	9.4	2011	16.9 Days	CHF 2700	Submit
Journal of Xenobiotics jox	6.8	5.3	2011	21.7 Days	CHF 1600	Submit
Kinases and Phosphatases kinasesphosphatases	-	-	2023	15.0 days *	CHF 1000	Submit
Pharmaceuticals pharmaceuticals	4.3	6.1	2004	14.6 Days	CHF 2900	Submit

* Median value for all MDPI journals in the second half of 2023.

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