Activation and Detoxification Enzymes Functions and Implications
There are many advances that have been made in the past decades towards the understanding of functions and implications of activation enzymes and detoxification enzymes. An organized, concise overview is needed for the readers who are initially exposed to
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Chang-Hwei Chen
Activation and Detoxification Enzymes Functions and Implications
Chang-Hwei Chen, Ph.D. Professor, Institute for Health and the Environment Former Professor, Department of Biomedical Sciences University at Albany, State University of New York Albany, NY, USA [email protected]
ISBN 978-1-4614-1048-5 e-ISBN 978-1-4614-1049-2 DOI 10.1007/978-1-4614-1049-2 Springer New York Dordrecht Heidelberg London Library of Congress Control Number: 2011939743 © Springer Science+Business Media, LLC 2012 All rights reserved. This work may not be translated or copied in whole or in part without the written permission of the publisher (Springer Science+Business Media, LLC, 233 Spring Street, New York, NY 10013, USA), except for brief excerpts in connection with reviews or scholarly analysis. Use in connection with any form of information storage and retrieval, electronic adaptation, computer software, or by similar or dissimilar methodology now known or hereafter developed is forbidden. The use in this publication of trade names, trademarks, service marks, and similar terms, even if they are not identified as such, is not to be taken as an expression of opinion as to whether or not they are subject to proprietary rights. Printed on acid-free paper Springer is part of Springer Science+Business Media (www.springer.com)
This book is dedicated to my father and my mother
Preface
Humans are exposed to foreign compounds such as drugs, household products, and environmental chemicals by swallowing or breathing. Also, food is considered a foreign compound. Such foreign compounds can be nonessential and nonfunctional to life, and are commonly referred to as xenobiotics. Some xenobiotics are not toxic; however, many of them are potentially toxic or become toxic after conversion to metabolic intermediates. A considerable number of foreign compounds belong to nonpolar, lipophilic substances. Lipophilic compounds are not soluble in water. Metabolic conversion of lipophilic foreign compounds to facilitate their removal from the body is essentially carried out by biochemical reactions catalyzed by two classes of foreign compound-metabolizing enzymes, namely, activation enzymes and detoxification enzymes. Activation enzyme-catalyzed functionalization reaction introduces a functional group to a lipophilic compound. Functionalization modifies many foreign compounds to form reactive intermediates capable of interacting with cellular components (proteins, DNA, and lipids), leading to a variety of conditions for diseases. Functionalized compounds are further metabolized through detoxification enzymecatalyzed reactions, which result in an increase in the solubility of parent compounds and an inactivation of metabolic intermediates, thus facilitating their excretion from the body. To minimize the exposure of potentially toxic metabolic intermediates, it is essential to keep them at a minimum level. Extensive investigations have revealed that foreign compound-metabolizing enzymes exhibit genetic polymorphisms. Variations in their activities
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