Slow-Onset Enzyme Inhibition
Slow-onset interactions between modifiers and their target enzymes are common in living cells and physiological fluids. This chapter aims at supporting the analysis of such interactions in the test tube by discussing the properties of various mechanisms a
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Kinetics of Enzyme-Modifier Interactions Selected Topics in the Theory and Diagnosis of Inhibition and Activation Mechanisms
Kinetics of Enzyme-Modifier Interactions
Antonio Baici
Kinetics of Enzyme-Modifier Interactions Selected Topics in the Theory and Diagnosis of Inhibition and Activation Mechanisms
123
Antonio Baici Department of Biochemistry University of Zurich Zurich, Switzerland
ISBN 978-3-7091-1401-8 DOI 10.1007/978-3-7091-1402-5
ISBN 978-3-7091-1402-5
(eBook)
Library of Congress Control Number: 2015942930 Springer Wien Heidelberg New York Dordrecht London © Springer-Verlag Wien 2015 This work is subject to copyright. All rights are reserved by the Publisher, whether the whole or part of the material is concerned, specifically the rights of translation, reprinting, reuse of illustrations, recitation, broadcasting, reproduction on microfilms or in any other physical way, and transmission or information storage and retrieval, electronic adaptation, computer software, or by similar or dissimilar methodology now known or hereafter developed. The use of general descriptive names, registered names, trademarks, service marks, etc. in this publication does not imply, even in the absence of a specific statement, that such names are exempt from the relevant protective laws and regulations and therefore free for general use. The publisher, the authors and the editors are safe to assume that the advice and information in this book are believed to be true and accurate at the date of publication. Neither the publisher nor the authors or the editors give a warranty, express or implied, with respect to the material contained herein or for any errors or omissions that may have been made. Printed on acid-free paper Springer-Verlag GmbH Wien is part of Springer Science+Business Media (www.springer.com)
To my students, Swiss Federal Institute of Technology and University of Zurich, 1972–2012
Foreword
Many drugs in current use owe their effectiveness to the fact that they are enzyme inhibitors. In addition, going back to the studies of invertase that Leonor Michaelis and his collaborators carried out at the beginning of the twentieth century, inhibitors have played a major role in efforts to understand the mechanisms that allow enzymes to fulfil their roles as catalysts. Bringing these two aspects together, we may note that understanding how inhibitors affect individual enzymes is a necessary step in understanding what happens when an enzyme that forms part of a metabolic pathway is inhibited in a living organism. Inhibitors and activators taken together are classified as enzyme modifiers, the subject of Antonio Baici’s masterly book. Activators have been less intensively studied than inhibitors over the years, but they are also important and should not be forgotten. It surely follows, therefore, that kinetic characterization of these effects is vital both for understanding enzyme mechanisms and for drug development. Yet the treatment in most general textbooks of biochemistry (with Henry Mahler and Eugene Cord
