Isoenzymes
The increased interest in multiple forms of enzymes that began with the application of new methods of fractionation to preparations of enzymes and other proteins some 25 years ago led quickly to an appreciation that the existence of enzymes in multiple fo
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Isoenzymes D.W. MOSS
Professor of Clinical Enzymology Royal Postgraduate Medical School Hammersmith Hospital London
London
New York
Chapman and Hall
First published in 1982 by Chapman and Hall Ltd 11 New Fetter Lane, London EC4P 4EE Published in the USA by Chapman and Hall in association with Methuen, Inc. 733 Third Avenue, New York NY 10017
©
1982, Chapman and Hall Ltd
Softcover reprint of the hardcover 1st edition 1982
All rights reserved. No part of this book may be reprinted, or reproduced or utilized in any form or by any electronic, mechanical or other means, now known or hereafter invented, including photocopying and recording, or in any information storage and retrieval system, without permission in writing from the publisher.
British Library Cataloguing in Publication Data Moss, D.W. Isoenzymes. 1. Isoenzymes 574.19'25 QP601 lSBN-13: 978-94-009-5888-3 e-1SBN-13: 978-94-009-5886-9 001: 10.1007/978-94-009-5886-9
iv
Contents
Preface
ix
1.
Multiple Forms of Enzymes and the Emergence of the Isoenzyme Concept
2.
Origins and Structures of Multiple Forms of Enzymes Origins of isoenzymes Isoenzymes determined by multiple gene loci Isoenzymes determined by multiple alleles Hybrid isoenzymes Structural differences between isoenzymes and their investigation Differences in primary structure Peptide maps and partial sequences Selective chemical or enzymic modification Secondary and tertiary structures Quaternary structure Non-isoenzymic multiple forms of enzymes Variations in covalent structures Variations in non-polypeptide constituents Non-covalent modifications of enzyme structure
3.
Differences in Properties between Multiple Forms of Enzymes Catalytic differences between multiple forms of enzymes Differences in specific activity Differences in reaction with substrates
v
9 9 11 13
15 17 17 17 20 22 26 30 31 33 36
39 40 40
41
Selective inhibition of isoenzymes Differences between isoenzymes in other catalytic properties Physicochemical differences between multiple forms of enzymes Differences in ionic characteristics Differences in stability Differences in molecular size Immunochemical differences between multiple forms of enzymes Immunoanalytical procedures useful in studies of multiple forms of enzymes Properties of multiple forms of enzymes: general considerations Differences in catalytic properties Differences in antigenicity Differences in resistance to inactivation Differences in charge or size
4.
Distribution and Biological Functions of Multiple Forms of Enzymes Distribution of enzymes determined by multiple gene loci Intracellular distribution of isoenzymes Effect of multiple allelism on isoenzyme distribution Physiological function of multiple forms of enzymes Compartmentalization of metabolic pathways in tissues and organelles Functions of other multiple forms of enzymes
48 53 54 54 63 68
69 73 81 82 83 84 85
87 87 95 108 108 109 114
5.
Multiple Forms of Enzymes in Phylogeny and Genetics Gene duplication and the evolution of multiple loci Isoenzymes of lactate dehydrogena
