Chang-Hwei Chen - Xenobiotic Metabolic Enzymes: Bioactivation and Antioxidant Defense

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Xenobiotics are commonly referred to as foreign compounds that humans digest or inhale and are not produced by the body, such as foods, drugs, other chemicals, and air pollutants. Metabolic conversion of foreign compounds to facilitate their removal from the body is catalyzed by activation and detoxification enzymes. These enzymes are essential for bioactivation and detoxification of foreign compounds. Many xenobiotics are non-toxic in nature; however, some of them become cytotoxic or carcinogenic after metabolic conversion. Reactive intermediates or metabolites generated during metabolic conversion are generally electrophilic in nature and are either cations or neutral compounds, including reactive oxygen species and free radicals.

Metabolic reactive intermediate-mediated oxidative stress can cause damages to cellular components such as impairment of protein functions, membrane lipid peroxidation, and formation of DNA adduct. Oxidative stress plays a crucial role in the pathogenesis processes that attribute to various disease conditions. Detoxification enzymes and antioxidants act as defense mechanisms against metabolic reactive intermediates or metabolites. Nuclear factor erythroid-2-related factor 2 (Nrf2)antioxidant response element pathway is critical to the mechanism of action of detoxification enzymes.

Important factors in contributing to individual variations in response to xenobiotics-mediated toxicity and carcinogenesis include genetic polymorphisms of metabolic enzymes, environmental factor, and lifestyle. Extensive investigations in the past decades have discovered a variety of chemical compounds that are capable of modulating metabolic enzymes for health benefits. Many of them are present in diets, such as sulfur- and non-sulfur-containing compounds, organosulfur compounds, flavonoids and carotenoids in vegetables, polyphenols and triterpenes in fruits, polyphenols in green tea, and unsaturated fatty acids in algae.

This book addresses the above subjects in broad scope with emphasis on biochemical and biomedical aspects and their recent advances. It can be used as supplemental text materials for senior undergraduates and graduate students in the areas of biochemistry, biomedical sciences, pharmacology, and environmental sciences. Researchers may also be interested in this book to gain knowledge on foreign compound metabolic enzymes and their health implications. There are 19 chapters in this book, including those that are extensively updated and revised from my 2012 Springer book. A bibliography is provided in each chapter, where references are cited for readers who wish to pursue topics in more detail.

The author wishes to thank Professor David Carpenter, Director of the Institute of Health and the Environment, University at Albany, for his encouragement and suggestions, and Professor Norman L. Strominger of Albany Medical College for his suggestions and comments. The author also wishes to express appreciation to the editorial board at Springer Nature for their assistance.