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Morris Volume 50: PATHOPHYSIOLOGICAL ASPECTS OF CANCER EPIDEMIOLOGY Editors: G. Mathe and P. Reizenstein Volume 51: FRONTIERS IN HISTAMINE RESEARCH Editors: C. R. Ganellin and J. C. Schwartz Volume 52: ORO-FACIAL PAIN AND NEUROMUSCULAR DYSFUNCTION Editors: I. Klineberg and B. Sessle Volume 53: THE PINEAL GLAND: ENDOCRINE ASPECTS Editors: G. M. Brown and S. D. Wainwright Volume 54: OXYGEN TRANSPORT IN RED BLOOD CELLS Editor: C. Nicolau Volume 55: GERM CELL TUMOURS II Editors: W. G. Jones, A. Milford Ward and C. K. Anderson Volume 56: RECENT TRENDS IN MEDICAL GENETICS Editors: K. M. Marimuthu and P. M. Gopinath OXYGEN TRANSPORT IN RED BLOOD CELLS Proceedings of the 12th Aharon Katzir Katchalsky Conference, Tours, France, 4-7 April 1984 Editor: CLAUDE NICOLAU Centre de Biophysique MoJecuJaire, Orleans, France PERGAMON PRESS OXFORD · NEW YORK · TORONTO · SYDNEY · FRANKFURT U.K. Pergamon Press Ltd., Headington Hill Hall, Oxford OX3 OBW, England U.S.A. Pergamon Press Inc., Maxwell House, Fairview Park, Elmsford, New York 10523, U.S.A. CANADA Pergamon Press Canada Ltd., Suite 104, 150 Consumers Road, Willowdale, Ontario M2J 1P9, Canada AUSTRALIA Pergamon Press (Aust.) Pty. Ltd., P.O. Box 544, Potts Point, N.S.W. 2011, Australia FEDERAL REPUBLIC Pergamon Press GmbH, Hammerweg 6, OF GERMANY D-6242 Kronberg, Federal Republic of Germany JAPAN Pergamon Press Ltd., 8th Floor, Matsuoka Central Building, 1-7-1 Nishishinjuku, Shinjuku-ku, Tokyo 160, Japan BRAZIL Pergamon Editora Ltda., Rua Ega de Queiros, 346, CEP 04011, Säo Paulo, Brazil PEOPLE'S REPUBLIC Pergamon Press, Qianmen Hotel, Beijing, OF CHINA People's Republic of China Copyright © 1986 Pergamon Press Ltd. AJJ Rights Reserved. No part of this publication may be re- produced, stored in a retrieval system or transmitted in any form or by any means: electronic, electrostatic, magnetic tape, mechanical, photocopying, recording or otherwise, without per- mission in writing from the publishers. First edition 1986 Library of Congress Cataloging in Publication Data Aharon Karzir-Katchalsky conference (12th: 1984: Tours, France) Oxygen transport in red blood cells. (Advances in the biosciences; v. 54) Includes index. 1. Oxygen transport (Physiology)—Congresses. I. Nicolau, Claude. II. Title. III. Series. [DNLM: 1. Erythrocytes—congresses. 2. Oxygen—blood— congresses. 3. Oxygen—metabolism—congresses. W3 Ad244 v. 54/WH 150 A285 19840] QP99.3.09A38 1984 612'.1111 85-12433 British Library Cataloguing in Publication Data Aharon Katzir-Katchalsky Conference {12th : 1984 : Tours) Oxygen transport in red blood cells : proceedings of the 12th Aharon Katzir-Katchalsky Conference, Tours, France, April 4—7, 1984. — (Advances in the biosciences; 54) 1. Oxygen transport (Physiology) I. Title II. Nicolau, Claude III. Series 599'.01'1 QP99.3.09 ISBN 0-08-030800-7 In order to make this volume available as economically and as rapidly as possible the typescript has been reproduced in its original form. This method unfortunately has its typographical limitations but it is hoped that they in no way distract the reader. Printed in Great Britain by A. Wheaton £r Co. Ltd., Exeter Foreword To mark the 12th year since Aharon Katzir-Katchalsky was killed and continuing a tradition established within the international scientific community, the Centre National de la Recherche Scientifique together with the Weizmann Institute of Science, the Aharon Katzir Katchalsky Center or- ganized in Tours, France, a Meeting on 0-transport by the Red Blood Cells. 2 Many distinguished workers in the field attended this Meeting. Like the previous ones and like Aharon's laboratory, this Meeting was an encounter place of biophysicists, biochemists, hematologists, physicians, physiolo- gists. This volume presents the invited lectures delivered at this Meeting. A few of them deal with the influence of the Hb-0 dissociation curve on 0 2 2 transport by red blood cells. Other aspects are covered as well and they bring a significant degree of novelty. Thanks are due to all the authors for that. The financial support of the CNRS, the Katzir-Katchalsky Center, Smith Kline French Laboratories (Philadelphia, PA, USA) and of the Pasteur- Weizmann Committee is gratefully acknowledged. Christiane David and Jeannine Florian typed the text and Edith Barre compiled the Subject Index. My best thanks go to them. Last but not least Pergamon Press with their usual competence and efficiency and with unusual patience printed this volume. Claude NICOLAU v ERRATUM OXYGEN TRANSPORT IN RED BLOOD CELLS 12th Aharon Katzir-Katchalsky Meeting Tours, France, 4-7 April 1984 The editor would like to acknowledge the sponsorship of the following: Centre Regional de Transfusion Sanguine, Tours Biotest, France Institut Merieux, France Travenol, France Hoechst-Behring, France Laboratories Pieree Fabre, France which contributed greatly to the success of the meeting. List of Contributors Dr Toshio Asakura Dr B Chaillot Division of Hematology Faculte des Sciences Pharmaceutiques The Children's Hospital et Biologiques of Philadelphia 21033 Dijon Cedex 34th Street and Civic France Center Boulevard Philadelphia Dr 0 Charansonney Pennsylvania 19104 Laboratory of Biophysics USA Hopital Fernand Widal 200 Rue du Faubourg Saint-Denis Dr G Avenard 75010 Paris Centre National de Transfusion France Sanguine Paris Dr M Chassaigne France Centre Regional De Transfusion Sanguine Dr P Boivin UA 596 C.N.R.S. Inserm U 160 2 Boulevard Tonnele Hopital Beaujon 37044 Itours 92118 Clichy Cedex France France Dr C Crone Dr M A Borchardt Institute of Medical Physiology Department of Medicine Department A university of Wisconsin University of Copenhagen Madison The Panum Institute Wisconsin 53792 Blegdamsvej 3 c USA DK-2200 Copenhagen N Denmark Dr George H Brewer Department of Human Genetics Dr E Dellacherie University of Michigan Ecole Nationale Superieure Des Ann Arbor Industries Chemiques MI 48104 CNRS ERA 23 USA 54042 Nancy Cedex France IX X List of Contributors Dr Robert D Dick Dr J L Martin Department of Internal Medicine Laboratory of Biophysics university of Michigan Hopital Fernand Widal Ann Arbor 200 Rue du Faubourg Saint-Denis MI 48104 75010 Paris USA France Dr M Duruble Dr A Mayevsky Laboratory of Biophysics Department of Life Sciences Hopital Fernand Widal Bar-Ilan university 200 Rue du Faubourg Saint-Denis Ramat-Gan 52 100 75010 Paris Israel France Dr C Nicolau Dr M A Duvelleroy Centre de Biophysique Moleculaire Laboratory of Biophysics 45045 Orleans Hopital Fernand Widal France 200 Rue du Faubourg Saint-Denis 75010 Paris Dr L Philippe France Dept of Nuclear Medicine and ultrasound Dr Y Gauduel Trousseau University Hospital Laboratory of Biophysics Tours Hopital Fernand Widal France 200 Rue du Faubourg Saint-Denis 75010 Paris Dr George K Radda France Dept of Biochemistry university of Oxford Dr Michael P Hlastala South Iferks Road Depts of Physiology & Biophysics Oxford University of Washington Seattle Dr Michael P Reilly WA 98195 Division of Hematology USA The Children's Hospital of Philadelphia 34th Street & civic Center Bouleavard Dr Ernesto E Di lorio Philadelphia Laboratorium fuer Biochemie I Pennsylvania 19104 Eidgenoessische Technische USA Hochschule-Eth-Zentrum Uhiversitaetsstrasse 16 Dr C Ropars 8092 Zurich CNRS ERA 697 and Centre Regional Switzerland de Transfusion Sanguine 37000 Tours Er R Itti France Dept of Nuclear Medicine and Ultrasound Dr J F Stolz Trousseau University Hospital Centre Regional de Transfusion Tours Sanguine et D'Hematologie France R.N. 74 54500 Vandoeuvre-Les-Nancy Dr P Labrude France Centre Regional de Transfusion Sanguine et D'Hematologie Dr 0 Stucker R.N. 74 Laboratory of Biophysics 54500 Vandoeuvre-Les-Nancy Hopital Fernand Widal France 200 Rue du Faubourg Saint-Denis 75010 Paris France List of Contributors xi Dr B Tannenbaum Dr C Vigneron Dept of life Sciences Centre Regional de Transfusion Bar-Ilan university Sanguine et D'Hematologie Ramat-Gan 52 100 R.N. 74 Israel 54500 Vandoeuvre-Les-Nancy France Dr B Teisseire Inserm U 138 & Service Dr Kaspar H Winterhalter D' Explorat ions Fonctionnelles Laboratorium fuer Biochemie I Hopital Henri Mondor Eidgenoessische Technische 94010 Creteil Hochschul e-Eth-Zentrum France Universitaetsstrasse 16 8092 Zurich Dr R Trouve Switzerland Laboratory of Biophysics Hopital Fernand Widal Dr R D Woodson 200 Rue du Faubourg Saint-Denis Department of Medicine 75010 Paris university of Wisconsin France Madison Wisconsin 53792 Dr C R Valeri USA Naval Blood Reserach Lab Boston University Dr E Yoles School of Medicine Department of Life Sciences Boston Bar-Ilan university MA 02132 Ramat-Gan 52 100 USA Israel Dr E Vicaut Dr N Zarchin Laboratory of Biophysics Department of Life Sciences Hopital Fernand Widal Bar-Ilan tiiiversity 200 Rue du Faubourg Saint-Denis Ramat-Gan 51 100 75010 Paris Israel France Dr C Vieilledent Inserm U 138 & Service D1Explorations Fonctionelles Hopital Henri Mondor 94010 Creteil France Influence of Heme Pocket Geometry on Ligand Binding to Heme Proteins K. H. Winterhalter and E. E. Di Iorio Laboratorium fuer Biochemie I, Eidgenoessische Technische Hochschule, ETH-Zentrum, Universitaetsstrasse 16, 8092 Zurich, Switzerland Oxygen binding, and its delivery to the place of consumption, is the continent in which the city of oxygen transport by red blood cells lies. The problem of oxygen transport is old, but new insight is gained every year. Table I gives an overview of the continent and the roads to and from the city. The levels of traffic regulation, as they are conceived presently, are also given. Table I - The levels of regulation of Op supply to tissues Compartment Level Some parameters A External 1. p0 Altitude 2 2. Aeration of alveolae State of Lung 3. Permeability of al- State of Lung veolae B Blood 1. 0 capacity Erythropoietin levels 2 2. 0 uptake by RBC Potency of circula- 2 tion, membrane per- meability, diffusion in cytoplasm, others? 3. 0 affinity of Genetic material, al- 2 hemoglobin losteric effectors, C0^o2,, ppHH,, others? 4. 0 dissociation in As for B and B-; 0 2 o tne periphery gradient C Intracellular 1. Myoglobin State of exercise, in tissues hormonal regulation 2. Uptake into orga- Diffusion, others? nelles (Mitochon- dria, microsomes, peroxysomes, plas- mamembranes 1 2 Κ. Η. Winterhalter and Ε. Ε. Di Iorio Oxygen, at its various places of consumption, is needed for a variety of different types of metabolism. They are summarized in table II. From this table it is evident that oxygen affects all walks of biochemistry in areobic organisms, from energy production to cancer. Table II - Types of metabolisms in which oxygen is paramount TvPe Main organelle Examples Energy metabo- Mitochondria Respiratory chain; lism Chloroplasts photosystem 1 and 2 Katabolic Peroxysomes Conversion of octanoate to H 0 ; D-amino acid break- 2 2 down; urate and L-alpha- hydroxy-acids metabolism Modification of Microsomes Synthesis of carcinogens metabolites and tumor promotors by te- rminal oxygenase systems; prostaglandin and adrena- lin synthesis Biosynthesis Cytoplasm Some steps of aminoacid and Katabolism katabolism, e.g. trypto- phane pyrrolase Bacterial kil- Plasmamembrane of Polymorphonuclear leuco- ling white cells; nat- cyte Superoxide synthetase ural killer cells As many of the regulatory mechanisms of oxygen transport by red blood cells (Table I.B) will be discussed by other participants of this conference, the topic of this talk is limited to the innermost events inside the hemoglobin molecule. The overall anatomy of a sperm whale myoglobin (SW-Mb) molecule (also representative of a hemoglobin chain) is given in fig. 1. For the binding to the heme-iron of a ligand molecule, coming from the solvent, at least three steps, characterized by energy barriers (Austin, et. al., 1975), must be distinguished: