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Conjugation Reactions In Drug Metabolism: An Integrated Approach

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‘The conjugations may well be the most important drug biotransformation reactions.’ Thus reads the first sentence in Chapter 1 of this book; and indeed, this may be little realized, if one compares the overwhelming attention paid to cytochrome P-450-mediated biotransformation with what is published on the conjugations. Yet, oxidative metabolism of xenobiotics is usually followed by conjugation of the group created by oxidation. Only then can these compounds be readily eliminated from the organism. In addition, xenobiotics carry many groups which are already acceptor groups for conjugation.

This volume summarizes the state of the art for the main conjugations. It should fill the gap between comprehensive monographs of single conjugations on one hand, and the more general reviews of drug metabolism, which often devote only a few pages to the conjugations (often considered to be just detoxication reactions) on the other.

The chapters on the various conjugations are the result of a collaborative effort of authors who are familiar with the biochemical aspect of the conjugation and those whose expertise is on the biotransformation in vivo. Therefore, the conjugation is treated as a whole, reflecting the importance of enzymology for the biotransformation of xenobiotics in vivo, in perfusions or in isolated cells.

Obviously, the conjugations are involved in the elimination of compounds present in the natural environment, for instance in food. In addition, and this is in fact the most studied aspect, they metabolize xenobiotics made by man, such as medicinal drugs, insecticides, etc. Moreover, many endogenous compounds, such as steroid hormones or prostaglandin derivatives, are substrates for certain forms of the transferases, so that these also play an important role in the homeostasis of the organism.

The chapters present an overview, without giving all the details. Also, most chapters contain a brief section on methodology to facilitate the choice of methods for experimental work.
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