Downloaded by 5.101.222.17 on October 30, 2016 | http://pubs.acs.org Publication Date: January 24, 1986 | doi: 10.1021/bk-1986-0299.pr001
PREFACE IN T H E FIELD O F XENOBIOTIC METABOLISM, the study of xenobiotic conjugation reactions has progressed through three phases. From 1840 (when hippuric acid biosynthesis was discovered) until the First World War, the primary field of study was xenobiotic conjugation reactions. A high point during this era was the formulation of the "chemical defense hypothesis" by C. P. Sherwin. After the 1930s, oxidative reactions became increasingly more important, and in the late 1970s cytochrome P450 and reactive oxidation products seemingly defined the limits of xenobiotic metabolism. Recently, however, interest in the properties and enzymology of formation of xenobiotic conjugates has increased. Numerous studies demonstrate that some xenobiotic conjugates are as active or more active than the parent compound. Thus, a complete assessment of the effects of xenobiotics must include evaluations of the formation and biological properties of xenobiotic conjugates. Xenobiotic conjugates can be divided into two classes—the principal conjugates that are commonly formed and the novel conjugates that are less commonly formed. Mammals, aquatic organisms, insects, and higher plants (as well as different organisms within each of these broad classes) form xenobiotic conjugates that have similarities as well as differences. Qualitative and quantitative differences in conjugation may profoundly alter the biological activity of certain xenobiotics. These differences in conjugation activity can be beneficial (e.g., herbicide selectivity) or may have adverse consequences (e.g., xenobiotic toxicity due to the absence of a conjugation system). These products must be isolated and unequivocally identified in order to fully evaluate the biological significance of xenobiotic conjugate formation. Novel xenobiotic conjugates may provide direct or indirect clues concerning the mode of action and the pharmacological and toxicological properties of certain xenobiotics. As the methods of separation and identification of polar conjugates improve and as a larger variety of xenobiotics are studied, spectacular modifications of principal conjugation mechanisms and many examples of novel xenobiotic conjugates are being discovered. Occasionally, no indication as to the involvement of a particular intermediate conjugation step can be gained by the identification of the structure of the terminal metabolite. These intermediate or "hidden" ix
Paulson et al.; Xenobiotic Conjugation Chemistry ACS Symposium Series; American Chemical Society: Washington, DC, 1986.
Downloaded by 5.101.222.17 on October 30, 2016 | http://pubs.acs.org Publication Date: January 24, 1986 | doi: 10.1021/bk-1986-0299.pr001
conjugates may remain undetected because of their transient nature. Questions concerning the biological significance of xenobiotic conjugates and the disposition of these compounds after they are formed must be answered. Therefore, the involvement of xenobiotic conjugate intermediates in carcinogenesis and the binding of certain xenobiotics to macromolecules are being studied. Finally, the widespread exposure of food plants to a great variety of xenobiotics makes this area one of current significance. The symposium upon which this book is based was organized to provide a critical review, evaluation, and summary of current information and technology relevant to xenobiotic conjugation chemistry. The highlights of this symposium are presented in this volume. G A Y L O R D D. PAULSON
Metabolism and Radiation Research Laboratory Agricultural Research Service U.S. Department of Agriculture Fargo, ND 58105 JOHN CALDWELL
Department of Pharmacology St. Mary's Hospital Medical School University of London London W2 1PG, England DAVID H. H U T S O N
Shell Research Ltd. Sittingbourne Kent ME9 8AG, England JULIUS J. M E N N
National Program Staff Agricultural Research Service U.S. Department of Agriculture Beltsville, M D 20705 October 1985
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Paulson et al.; Xenobiotic Conjugation Chemistry ACS Symposium Series; American Chemical Society: Washington, DC, 1986.
