Hemoglobin and Red Cell Structure and Function: Proceedings of the Second International Conference on Red Cell Metabolism and Function held at the University of Michigan Ann Arbor, April 27–29, 1972

532 Pages·1972·22.66 MB·English

by  M. F. Perutz

HEMOGLOBIN AND RED CELL
STRUCTURE AND FUNCTION
ADV ANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY
Editorial Board:
Nathan Back Chairman, Department of Biochemical Pharmacology, School of Pharmacy,
State University of New York, Buffalo, New York
N. R. Di Luzio Chairman, Department of Physiology, .
Tulane University School of Medicine, New Orleans, Louisiana
Alfred Gellhorn University of Pennsylvania Medical School, Philadelphia, Pennsylvania
Bernard Halpern College de France,
Director of the Institute of Immuno.Biology, Paris, France
Ephraim Katchalski Department of Biophysics, The Weizmann Institute of Science,
Rehovoth. Israel
David Kritchevsky Wistar Institute, Philadelphia, Pennsylvania
Abel Lajtha New York State Research Institute for Neurochemistry and Drug Addiction,
Ward's Island, New York
Rodolfo Paoletti Institute of Pharmacology, University of Milan, Milan,Italy
Volume 1
THE RETICULOENDOTHELIAL SYSTEM AND ATHEROSCLEROSIS
Edited by N. R. Di Luzio and R. Paoletti· 1967
Volume 2
PHARMACOLOGY OF HORMONAL POLYPEPTIDES AND PROTEINS
Edited by N. Back, L. Martini, and R. Paoletti· 1968
Volume 3
GERM·FREE BIOLOGY: Experimental and Clinical Aspects
Edited by E. A. Mirand and N. Back· 1969
Volume 4
DRUGS AFFECTING LIPID METABOLISM
Edited by W. L. Holmes, L. A. Carlson, and R. Paoletti· 1969
Volume 5
LYMPHATIC TISSUE AND GERMINAL CENTERS IN IMMUNE RESPONSE
Edited by L. Fiore·Donati and M. G. Hanna, Jr. • 1969
Volume 6
RED CELL METABOLISM AND FUNCTION
Edited by George J. Brewer· 1970
Volume 7
SURFACE CHEMISTRY OF BIOLOGICAL SYSTEMS
Edited by Martin Blank· 1970
Volume 8
BRADYKININ AND RELATED KININS: Cardiovascular, Biochemical, and
Neural Actions
Edited by F. Sicuteri, M. Rocha e Silva, and N. Back· 1970
Volume 9
SHOCK: Biochemical, Pharmacological, and Clinical Aspects
Edited by A. Bertelli and N. Back· 1970
Volume 10
THE HUMAN TESTIS
Edited by E. Rosemberg and C. A. Paulsen· 1970
Volume 11
MUSCLE METABOLISM DURING EXERCISE
Edited by B. Pemow and B. Sahin· 1971
Volume 12
MORPHOLOGICAL AND FUNCTIONAL ASPECTS OF IMMUNITY
Edited by K. Lindahl.Kiessling, G. AIm, and M. G. Hanna, Jr.· 1971
Volume 13
CHEMISTRY AND BRAIN DEVELOPMENT
Edited by R. Paoletti and A. N. Davison· 1971
Volume 14
MEMBRANE·BOUND ENZYMES
Edited by G. Porcellati and F. di Jeso • 1971
Volume 15
THE RETICULOENDOTHELIAL SYSTEM AND IMMUNE PHENOMENA
Edited by N. R. Di Luzio and K. Flemming· 1971
Volume 16A
THE ARTERY AND THE PROCESS OF ARTERIOSCLEROSIS: Pathogenesis
Edited by Stewart W oU • 1971
Volume 16B
THE ARTERY AND THE PROCESS OF ARTERIOSCLEROSIS: Measurement and
Modification
Edited by Stewart Wolf· 1971
Volume 17
CONTROL OF RENIN SECRETION
Edited by Tatiana A. Assaykeen • 1972
Volume 18
THE DYNAMICS OF MERISTEM CELL POPULATIONS
Edited by Morton W. Miller and Charles C. Kuehnert • 1972
Volume 19
SPHINGOLIPIDS, SPHINGOLIPIDOSES AND ALLIED DISORDERS
Edited by Bruno W. Volk and Stanley M. Aronson. 1972
Volume 20
DRUG ABUSE: Nonmedical Use of Dependence-Producing Drugs
Edited by Simon Btesh • 1972
Volume 21
VASOACTIVE POLYPEPTIDES
Edited by N. Back and F. Sicuteri • 1972
Volume 22
COMPARATIVE PATHOPHYSIOLOGY OF CIRCULATORY DISTURBANCES
Edited by Colin M. Bloor • 1972
Volume 23
THE FUNDAMENTAL MECHANISMS OF SHOCK
Edited by Lerner B. Hinshaw and Barbara G. Cox. 1972
Volume 24
THE VISUAL SYSTEM: Neurophysiology, Biophysics, and Their Clinical Applications
Edited by G. B. Arden. 1972
Volume 25
GLYCOLIPIDS, GLYCOPROTEINS, AND MUCOPOLYSACCHARIDES
OF THE NERVOUS SYSTEM
Edited by Vittorio Zambotti, Guido Tettamanti, and Mariagrazia Arrigoni. 1972
Volume 26
PHARMACOLOGICAL CONTROL OF LIPID METABOLISM
Edited by William L. Holmes, Rodolfo Paoletti,
and David Kritchevsky • 1972
Volume 27
DRUGS AND FETAL DEVELOPMENT
Edited by M. A. Klingberg, A. Abramovici, and J. Chemke .1972
Volume 28
HRMOGLOBIN AND RED CELL STRUCTURE AND FUNCTION
HEMOGLOBIN AND
RED CELL STRUCTURE
AND FUNCTION
Proceedings of the Second International Conference on Red Cell
Metabolism and Function h~ld at the University of Michigan
Ann Arbor, April 27-29, 1972
Edited by
George J. Brewer
Department of Human Genetics and Medicine
(Simpson Memorial Institute)
University of Michigan
Ann Arbor, Michigan
~ PLENUM PRESS • NEW YORK -LONDON • 1972
The Second International Conference on Red Cell Metabolism and
Function was sponsored in part by
Office of Naval Research (Contract #NOOOI4-72-C-0338)
Michigan Cancer Institute
The National Foundation
Abbott Laboratories
Library of Congress Catalog Card Number 72-86140
ISBN-13: 978-1-4684-3224-4 e-ISBN-13: 978-1-4684-3222-0
DOl: 10.1007/978-1-4684-3222-0
© 1972 Plenum Press, New York
Softcover reprint of the hardcover 1st edition 1972
A Division of Plenum Publishing Corporation
227 West 17th Street, New York, N.Y. 10011
United Kingdom edition published by Plenum Press, London
A Division of Plenum Publishing Company
Davis House (4th Floor), 8 Scrubs Lane, Harlesden, London,
NWIO 6SE, England
All rights reserved
No part of this publication may be reproduced in any form without
written permission from the publisher
PREFACE
Hemoglobin and the red cell have continued to set a dizzying
pace as the objects of research in the two and one-half year
interval since the First International Conference on Red Cell
Metabolism and Function. Most exciting perhaps, is a beginning
molecular attack on sickle cell disease. The story of the inter
action of red cell metabolism and oxygen transport has continued
to unfold, and we can now infer that patients with hypoxia usually
utilize red cell metabolic adjustments to improve oxygenation.
This puts the red cell squarely in the center of medical practice,
since much of medicine-heart, pulmonary, and blood diseases -
deals with inadequate oxygenation.
On April 27th through the 29th, 1972, crystallographers,
chemists, biochemists, physiologists, geneticists, and physi
cians from many medical disciplines met in the Towsley Center
for Continuing Medical Education at the University of Michigan,
Ann Arbor to present new data, to review recent developments,
and to try to piece together additional features of the red cell
puzzle. The meeting was dedicated to Dr. Francis John Worsley
Roughton, Professor Emeritus of Colloid Science, University of
Cambridge, England, in recognition of his numerous excellent
contributions to the understanding of hemoglobin and red cell
function.
The program got off to a good start with a paper from M. F.
Perutz, Nobel Laureate, on the structure of hemoglobin. Dr.
Perutz also key-noted the Conference with a special lecture on
heme-heme interaction. A number of fascinating papers were
presented on various aspects of hemoglobin, its structure, its
interaction with ligands such as oxygen, and its properties under
varying conditions. Red cell metabolism was considered, in
depth, from many viewpoints, including defects in uremia, inter
actions with serum phosphorous, male -female differences, the
role of catalase, genetic selection for quantitative variation, and
vii
viii PREFACE
mechanisms of glycolytic response to altitude stress and to
anemia. As with the first conference, a session was devoted to
the continuing assessment of the importance of decline in red
cell oxygen transport functional capacity during blood bank
storage. A session was also devoted to consideration of carbonic
anhydrase and carbon dioxide transport, and the interaction of
this area with oxygen transport.
A high point of the conference was the session on sickle cell
structure and function. Excellent papers were presented on
cyanate, including results of some early clinical trials which
look promising. A trial with oral urea in sickle cell disea.se
indicating possible usefulness of this approach was presented.
The antis ickling properties of carbamyl phosphate were also
discussed. The present status of prenatal diagnosis of sickle cell
disease, and the sickling phenomenon of deer erythrocytes, we re
other interesting topics. The discussions in the general area of
sickle cell disease and the mechanisms by which antis ickling
agents act were quite interesting because of the diversity and
expertise represented in the audience.
This volume contains the Proceedings of this second confer
ence. It includes the formal papers and much of the informal
discussion after the papers. It represents a compilation of the
present state of the art, and the status of current thinking, in
the various areas dis cussed above.
The Editor would like to acknowledge the great dedication and
assistance of Mrs. Nellie Gill in all phases of the Conference,
and pUblication of the volume. My wife, Lucia Feitler Brewer,
worked very hard on all aspects of Conference organization,
while keeping one hand busy in the laboratory. The continued
good spirits of these two in the face of ever-mounting details and
problems before and during the Conference, buoyed the rest of
us. I wish to thank Dr. Fred J. Oelshlegel, Jr. and Dr. John W.
Eaton for their counsel. Thanks are also due Ms. Nancy Noble,
Ms. Lorna Grindlay Moore, Mr. Eric Schoomaker, Mr. Conrad
Knutsen, Mr. Barry Sander, Dr. James V. Neel, Dr. C.J.D.
Zarafonetis, and Dean John Gronvall for their help and support.
The staff of Postgraduate Medicine, in particular Mr. Jack
Burmeister, Mr. Robert Richards, and Mrs. Lynne Bowbeer,
we re quite helpful. Mrs. Rena J ones and Mrs. Marion Wolfe
(and Mrs. Nellie Gill) dese rve much credit for struggling with
the discussion tapes. Financial support from the Office of Naval
Research, the National Foundation, the University of Michigan
Cancer Research Institute, and Abbott Laboratories made the
PREFACE ix
Conference possible. I thank the Biochemical Journal and the
Biochemical Society for us"e of the photograph of Dr. Roughton.
Plenum Press published the Proceedings of the First Conference
in record time, and judging from their helpfulness with this vol
ume, I anticipate another remarkable job.
THE EDITOR
May 19, 1972

DEDICATION
OF THE SECOND INTERNATIONAL CONFERENCE ON
RED CELL METABOLISM AND FUNCTION TO
DR. FRANCIS JOHN WORSLEY ROUGHTON
PROFESSOR EMERITUS OF COLLOID SCIENCE
UNIVERSITY OF CAMBRIDGE, ENGLAND
Dr. Roughton was born on June 6, 1899, in Kettering, an
industrial town in the midlands of England, His Roughton ances
tors were busy practicing doctors in the town for five genera
tions - father to son - from 1737 to 1933. As a boy he hoped, in
due course, to become the sixth of the series, but his physical
cons titution - notably a cardiac anomaly - made such an arduous
livelihood unwise. His father, the last of the five generations
of Kettering doctors, urged him in 1912 ins tead to become a
scientist with a special lean towards chemistry and its borders
with medical sciences, for which he saw a great future. It is
interesting to recall that Dr. Roughton's great grandfather
William, in a letter to home in 1799 from St. Bartholomew's
Hospital, London, where he was a medical student, apologized
for his extravagance in spending ten shillings and sixpence
(about 2 1/2 dollars at the current rate of exchange) on Lavoisier's
Treatise of Chemistry, which he considered lias indispensably
necessary for the understanding of the modern physiology".
In the course of his genealogical researches, to which he is
almost as devoted as to his scientific work, Dr. Roughton was
thrilled to discover in 1955 that he is directly descended, through
his Roughton great grandmother, from Daniel Harvey, one of
the brothers of William Harvey, the discoverer of the circula
tion of the blood. William Harvey, though married, was child
less so that as one of his numerous seven great nephews, Dr.
xi