Biochemical and Clinical Aspects of Hemoglobin Abnormalities

705 Pages·1978·16.09 MB·English

by  Winslow Caughey (Eds.)

BIOCHEMICAL
AND CLINICAL ASPECTS
OF HEMOGLOBIN
ABNORMALITIES
EDITED BY
WINSLOW S. CAUGHEY
Department of Biochemistry
Colorado State University
Fort Collins, Colorado
with Editorial Assistance by
Helen Caughey
ACADEMIC PRESS New York San Francisco London 1978
A Subsidiary of Harcourt Brace Jovanovich, Publishers
COPYRIGHT © 1978, BY ACADEMIC PRESS, INC.
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United Kingdom Edition published by
ACADEMIC PRESS, INC. (LONDON) LTD.
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Library of Congress Cataloging in Publication Data
Main entry under title:
Biochemical and clinical aspects of hemoglobin
abnormalities.
Proceedings of a symposium held on the Pingree Park
campus of Colorado State University, Oct. 2-7, 1977,
and co-sponsored by the Dept. of Biochemistry, Colorado
State University and the Sickle Cell Disease Branch of
the National Heart, Lung, and Blood Institute, National
Institutes of Health.
Includes index.
1. Hemoglobinopathy—Congresses. 2. Hemoglobin—
Congresses. 3. Sickle cell anemia—Congresses.
I. Caughey, WinslowS. II. Caughey, Helen.
III. Colorado. State University, Fort Collins, Dept.
of Biochemistry. IV. National Heart, Lung, and Blood
Institute. Sickle Cell Disease Branch.
RC641.7.H35B56 616.Γ5 78-19021
ISBN 0-12-164350-6
PRINTED IN THE UNITED STATES OF AMERICA
LIST OF CONTRIBUTORS
Numbers in parentheses indicate the pages on which the authors' contributions begin.
GARY K. ACKERS (527),1 Department of Biochemistry, University of
Virginia, Charlottesville, Virginia
JAMES 0. ALBEN (607,687), Department of Physiological Chemistry, Ohio
State University, College of Medicine, Columbus, Ohio
E. ANTONINI (17), CNR Center of Molecular Biology, Institutes of Chemistry
and Biochemistry, Faculty of Medicine, University of Rome, Rome, Italy
ARTHUR ARNONE (93), Department of Biochemistry, University of Iowa,
Iowa City, Iowa
HAROLD S. BALLARD (67), Manhattan VA Hospital, New York
VALERIA BALOGH-NAIR (143), Department of Chemistry, Columbia Uni-
versity, New York
GEORGE H. BARE (607), Department of Physiological Chemistry, Ohio
State University, College of Medicine, Columbus, Ohio
N. 0. BELSER (495), Department of Nematology, University of California,
Riverside, California
Y. BEUZARD (227,237), Unite de Recherches sur les Anemies, Höpital Henri
Mondor, Creteil, France
W. E. BLUMBERG (619), Departments of Molecular Pharmacology and
Molecular Biology, Albert Einstein College of Medicine of Yeshiva Uni-
versity, Bronx, New York, and Bell Laboratories, Murray Hill, New
Jersey
CELIA BONAVENTURA (109,647), Duke University Marine Laboratory,
Beaufort, North Carolina, and Duke University Medical Center, Durham,
North Carolina
JOSEPH BONAVENTURA (109,647), Duke University Marine Laboratory,
Beaufort, North Carolina, and Duke University Medical Center, Durham,
North Carolina
ROBERT M. BOOKCHIN (57,195), Department of Medicine, Albert Einstein
College of Medicine, Bronx, New York
Z. BRADIC (459), Department of Chemistry, New Mexico State University,
Las Cruces, New Mexico
1 Present address: McCollum-Pratt Institute, The Johns Hopkins University, Baltimore,
Maryland.
xi
XII List of Contributors
PATRICK D. BRILEY (93), Department of Biochemistry, University of Iowa,
Iowa City, Iowa
M. BRUNORI (17), CNR Center of Molecular Biology, Institutes of Chemistry
and Biochemistry, Faculty of Medicine, University of Rome, Rome, Italy
ENRICO BUCCI (299), Department of Biological Chemistry, University of
Maryland School of Medicine, Baltimore, Maryland
H. FRANKLIN BUNN (215), Peter Bent Brigham Hospital, Harvard Medical
School, Boston, Massachusetts
J. CACHELEUX (227), Unite de Recherches sur les Anemies, Höpital Henri
Mondor Creteil, France
R. W. CARRELL (583), Department of Clinical Biochemistry, University of
Cambridge, Cambridge, England
C. E. CASTRO (495), Department of Nematology, University of California,
Riverside, California
WINSLOW S. CAUGHEY (1,29,475), Department of Biochemistry, Colorado
State University, Fort Collins, Colorado
SAMUEL CHARACHE (29,577,687), Department of Medicine, Johns Hopkins
University School of Medicine, Baltimore, Maryland
A. K. CHURG (323), Department of Biophysics and Theoretical Biology,
Cummings Life Science Center, University of Chicago, Chicago, Illinois
J. THADDEUS COIN (559), Department of Biochemistry, Rice University,
Houston, Texas
R. CONRAD (459), Department of Chemistry, New Mexico State University,
Las Cruces, New Mexico
G. LARRY COTTAM (695), Department of Biochemistry, The University of
Texas Health Science Center at Dallas, Southwestern Medical School,
Dallas, Texas
RICHARD H. CREPEAU (389), Section of Biochemistry, Molecular and Cell
Biology, Cornell University, Ithaca, New York
R. S. DANZIGER (323), Department of Biophysics and Theoretical Biology,
Cummings Life Science Center, University of Chicago, Chicago, Illinois
HILLARD DAVIS (77), Harlem Hospital Center, Columbia University, Com-
prehensive Sickle Cell Center, New York
D. J. A. de WAAL (459), Department of Chemistry, New Mexico State Uni-
versity, Las Cruces, New Mexico
E. DI IORIO (17), Laboratory of Molecular Biology, University of Camerino,
Camerino, Italy
GENE DYKES (389), Section of Biochemistry, Molecular and Cell Biology,
Cornell University, Ithaca, New York
D. R. EATON (459), Department of Chemistry, New Mexico State University,
Las Cruces, New Mexico
WILLIAM A. EATON (443), Laboratory of Chemical Physics, National Insti-
tute of Arthritis, Metabolism, and Digestive Diseases, National Institutes
of Health, Bethesda, Maryland
List of Contributors XIII
STUART J. EDELSTEIN (389), Section of Biochemistry, Molecular and Cell
Biology, Cornell University, Ithaca, New York
PAULA M. D. FITZGERALD (165),2 The Thomas C. Jenkins Department of
Biophysics, Johns Hopkins University, Baltimore, Maryland
R. FLÜCKIGER (205), Friedrich Miescher-Institut, Basel, Switzerland
CLARA FRONTICELLI (299), Department of Biological Chemistry, University
of Maryland School of Medicine, Baltimore, Maryland
S. D. FULLER (311), Department of Biophysics and Theoretical Biology,
Cummings Life Science Center, University of Chicago, Chicago, Illinois
M. C. GAREL (237), Unite de Recherches sur les Anemies, Hopital Henri
Mondor, Creteil, France
H. T. GAUD (535), Department of Chemistry, University of Colorado,
Boulder, Colorado
G. GIACOMETTI (17), CNR Center of Molecular Biology, Institutes of Chem-
istry and Biochemistry, Faculty of Medicine, University of Rome, Rome,
Italy
S. J. GILL (535), Department of Chemistry, University of Colorado, Boulder,
Colorado
JONATHAN C. HANSON (165),3 The Thomas C. Jenkins Department of
Biophysics, Johns Hopkins University, Baltimore, Maryland
P. C. HARRINGTON (459), Department of Chemistry, New Mexico State
University, Las Cruces, New Mexico
MARGARET HARRIS (413), Departments of Biochemistry and Medicine,
State University of New York at Buffalo, VA Hospital, Buffalo, New York
W. HASSAN (237), Unite de Recherches sur les Anemies, Hopital Henri
Mondor, Creteil, France
CHIEN HO (179), Department of Biological Sciences, University of Pittsburgh,
Pittsburgh, Pennsylvania
JAMES HOFRICHTER (421,443), Laboratory of Chemical Physics, National
Institute of Arthritis, Metabolism, and Digestive Diseases, National Insti-
tutes of Health, Bethesda, Maryland
J. M. HOLT (475), Department of Biochemistry, Colorado State University,
Fort Collins, Colorado
ROBERT A. HOUTCHENS (1,29,475), Department of Biochemistry, Colorado
State University, Fort Collins, Colorado
KATHRYN M. JOHN (335), Division of Hematology and Oncology, Depart-
ment of Medicine, Children's Hospital Medical Center and Sidney Färber
Cancer Institute, Harvard Medical School, Boston, Massachusetts
2Present address: Department of Biological Chemistry, The Milton S. Hershey Medical
Center, The Pennsylvania State University, Hershey, Pennsylvania.
3Present address: Department of Biology, Brookhaven National Laboratory, Upton,
New York.
XIV List of Contributors
MARYANN McD. JONES (251), Department of Chemistry, Georgetown
University, Washington, D.C.
ROBIN A. KAROL (413),4 Departments of Biochemistry and Medicine, State
University of New York at Buffalo, VA Hospital, Buffalo, New York
MARTIN KARPLUS (515), Department of Chemistry, Harvard University,
Cambridge, Massachusetts
YUSUF KHAKOO (77), Harlem Hospital Center, Columbia University, Com-
prehensive Sickle Cell Center, New York
STEVE KOWALCZYKOWSKI (251), Department of Chemistry, Georgetown
University, Washington, D.C.
R. KRISHNAMOORTHY (583), Institut de Pathologie Moleculaire, Universite
de Paris, Paris, France
LEON C. LANDAU (57), Department of Medicine, Albert Einstein College of
Medicine, Bronx, New York
AMOS LANIR (29), Department of Biochemistry, Colorado State University,
Fort Collins, Colorado
GEORGE LAPENNAS (109), Duke University Marine Laboratory, Beaufort,
North Carolina, and Duke University Medical Center, Durham, North
Carolina
HERMANN LEHMANN (505), Department of Biochemistry, University of
Cambridge, Cambridge, England
P. A. LIU (353), Hematology Research Laboratory, St. Vincent Hospital,
University of Massachusetts Medical School, Worcester, Massachusetts
S. C. LIU (353), Hematology Research Laboratory, St. Vincent Hospital,
University of Massachusetts Medical School, Worcester, Massachusetts
WARNER E. LOVE (165), The Thomas C. Jenkins Department of Biophysics,
Johns Hopkins University, Baltimore, Maryland
SAMUEL E. LUX (335), Division of Hematology and Oncology, Department
of Medicine, Children's Hospital Medical Center and Sidney Färber
Cancer Institute, Harvard Medical School, Boston, Massachusetts
MELISENDA J. McDONALD (215), Peter Bent Brigham Hospital, Harvard
Medical School, Boston, Massachusetts
P. MACHADO (237), Unite de Recherches sur les Anemies, Höpital Henri
Mondor, Creteil, France
M. W. MAKINEN (311,323), Department of Biophysics and Theoretical
Biology, Cummings Life Science Center, University of Chicago, Chi-
cago, Illinois
JAMES M. MANNING (665,687), The Rockefeller University, New York
I. MAX-AUDIT (237), Unite de Recherches sur les Anemies, Höpital Henri
Mondor, Creteil, France
JOHN C. MAXWELL (29), Department of Biochemistry, Colorado State
University, Fort Collins, Colorado
4Present address: Department of Microbiology and Immunology, Albert Einstein College
of Medicine, Bronx, New York.
List of Contributors xv
ALLEN P. MINTON (545), Laboratory of Biophysical Chemistry, National
Institute of Arthritis, Metabolism, and Digestive Diseases, National Insti-
tutes of Health, Bethesda, Maryland
PATRICK P. MOH (607), Department of Physiological Chemistry, Ohio State
University, College of Medicine, Columbus, Ohio
F. MOLKO (227), Unite de Recherches sur les Anemies, Höpital Henri
Mondor, Creteil, France
RONALD L. NAGEL (57,195), Department of Medicine, Albert Einstein
College of Medicine, Bronx, New York
KOJI NAKANISHI (143), Department of Chemistry, Columbia University,
New York
CLAYTON L. NATTA (143), Department of Medicine and Pathology, College
of Physicians and Surgeons, Columbia University, New York, and Sickle
Cell Center, Harlem Hospital, New York
ALAN M. NIGEN (665,687), The Rockefeller University, New York
ROBERT W. NOBLE (401,413), Departments of Biochemistry and Medicine,
State University of New York at Buffalo, VA Hospital, Buffalo, New York
C. T. NOGUCHI (129), Laboratory of Chemical Biology, National Institute of
Arthritis, Metabolism, and Digestive Diseases, National Institutes of
Health, Bethesda, Maryland
BARRY E. NORTH (591), Biology Department, Brookhaven National Labora-
tory, Upton, New York
E. OLIVAS (459), Department of Chemistry, New Mexico State University,
Las Cruces, New Mexico
JOHN S. OLSON (559), Department of Biochemistry, Rice University,
Houston, Texas
J. PALEK (353), Hematology Research Laboratory, St. Vincent Hospital,
University of Massachusetts Medical School, Worcester, Massachusetts
J. PEISACH (619), Departments of Molecular Pharmacology and Molecular
Biology, Albert Einstein College of Medicine of Yeshiva University,
Bronx, New York, and Bell Laboratories, Murray Hill, New Jersey
RUSSELL R. PENNELLY (401), Departments of Biochemistry and Medicine,
State University of New York at Buffalo, VA Hospital, Buffalo, New York
M. F. PERUTZ (1), MRC Laboratory of Molecular Biology, Cambridge,
England
S. E. V. PHILLIPS (1), MRC Laboratory of Molecular Biology, Cambridge,
England
DAR LEEN F. POWARS (151), Department of Pediatrics, University of
Southern California, School of Medicine, Los Angeles, California
J. M. QUINN (311), Department of Biophysics and Theoretical Biology,
Cummings Life Science Center, University of Chicago, Chicago, Illinois
HELEN M. RANNEY (509), Department of Medicine, University of California,
San Diego, La Jolla, California
XVI List of Contributors
WILLIAM M. RINGLE (165),5 The Thomas C. Jenkins Department of Bio-
physics, Johns Hopkins University, Baltimore, Maryland
J. ROSA (237), Unite de Recherches sur les Anemies, Höpital Henri Mondor,
Creteil, France
PHILIP D. ROSS (629), Laboratory of Molecular Biology, National Institute
of Arthritis, Metabolism, and Digestive Diseases, National Institutes of
Health, Bethesda, Maryland
WILLIAM E. ROYER, JR. (165), The Thomas C. Jenkins Department of
Biophysics, Johns Hopkins University, Baltimore, Maryland
IRINA M. RUSSU (179), Department of Biological Sciences, University of
Pittsburgh, Pittsburgh, Pennsylvania
A. N. SCHECHTER (129), Laboratory of Chemical Biology, National Institute
of Arthritis, Metabolism, and Digestive Diseases, National Institutes of
Health, Bethesda, Maryland
BENNO P. SCHOENBORN (591), Biology Department, Brookhaven National
Laboratory, Upton, New York, and MRC Laboratory of Molecular Biol-
ogy, Cambridge, England
WALTER A. SCHROEDER (151), Division of Chemistry and Chemical Engi-
neering, California Institute of Technology, Pasadena, California
W. A. SCHWARTZ (129), Laboratory of Chemical Biology, National Institute
of Arthritis, Metabolism, and Digestive Diseases, National Institutes of
Health, Bethesda, Maryland
NURITH SHAKLAI (509), Department of Medicine, University of California,
San Diego, La Jolla, California
KATSUNORI SHIBATA (695), Department of Biochemistry, The University
of Texas Health Science Center at Dallas, Southwestern Medical School,
Dallas, Texas
JEANNE A. SMITH (77), Harlem Hospital Center, Columbia University,
Comprehensive Sickle Cell Center, New York
JACINTO STEINHARDT (251), Department of Chemistry, Georgetown Uni-
versity, Washington, D.C.
S. SUBRAMANIAN (629), Laboratory of Molecular Biology, National Insti-
tute of Arthritis, Metabolism, and Digestive Diseases, National Institutes
of Health, Bethesda, Maryland
A. TSAPIS (227), Centre Hayem, Höpital Saint-Louis, Paris, France
P. W. TUCKER (1),6 MRC Laboratory of Molecular Biology, Cambridge,
England
YOSHIHIRO UEDA (57), Department of Medicine, Albert Einstein College of
Medicine, Bronx, New York
5Present address: Anthropology Department, Tulane University, New Orleans, Louisiana.
6Present address: University of Wisconsin-Madison, Laboratory of Genetics, Madison,
Wisconsin.
List of Contributors XVII
ROLAND VALDES, JR. (527), Department of Biochemistry, University of
Virginia, Charlottesville, Virginia
RUTH S. WADE (495), Department of Nematology, University of California,
Riverside, California
W. J. WALLACE (475),7 Department of Biochemistry, Colorado State Uni-
versity, Fort Collins, Colorado
MICHAEL R. WATERMAN (695), Department of Biochemistry, The Univer-
sity of Texas Health Science Center at Dallas, Southwestern Medical
School, Dallas, Texas
T. E. WELLEMS (311), Department of Biophysics and Theoretical Biology,
Cummings Life Science Center, University of Chicago, Chicago, Illinois
S. L. WHITE (311), Department of Biophysics and Theoretical Biology,
Cummings Life Science Center, University of Chicago, Chicago, Illinois
R. G. WILKINS (459), Department of Chemistry, New Mexico State Univer-
sity, Las Cruces, New Mexico
ROBERT M. WINSLOW (369), Clinical Hematology Branch, National Heart,
Lung, and Blood Institute, National Institutes of Health, Bethesda,
Maryland
C. C. WINTERBOURN (583), Pathology Department, Christchurch Hospital,
Christchurch, New Zealand
K. H. WINTERHALTER (17,205),8 Friedrich Miescher-Institut, Basel, Switzer-
land
ROBERT WOODY (279), Department of Biochemistry, Colorado State Uni-
versity, Fort Collins, Colorado
JUAN YGUERABIDE (509), Department of Biology, University of California,
San Diego, La Jolla, California
TAKASHI YONETANI (123), Department of Biochemistry and Biophysics,
University of Pennsylvania School of Medicine, Philadelphia, Penn-
sylvania
7Present address: Department of Chemistry, University of Regina, Regina, Saskatchewan,
Canada.
8Present address: Laboratorium für Biochemie, Eidgenössische Technische Hochschule,
Zurich, Switzerland.
PREFACE
With more than 250 abnormal human hemoglobins now known, and the
number increasing rapidly, and with the structures, properties, and reactions
of these hemoglobins being elucidated in ever increasing detail, the time was
appropriate to convene a conference to evaluate in detail present views of
the biochemical, biophysical, and pathophysiological consequences of these
amino acid substitutions. To this end an international group of prominent
workers in the many facets of this field (biochemists, biophysicists, and
hematologists) met for six days on the Pingree Park Campus of the Colorado
State University, immediately north of Rocky Mountain National Park, for
the presentation and discussion of papers on the abnormal human hemo-
globins. The results were worthwhile, indeed. Many new findings were
reported; a host of new ideas, and newly arranged collaborations between
laboratories, resulted; valuable criticisms of ideas, old and new, were offered
in discussion.
The topics covered include the effects of amino acid substitutions (1) upon
structures: in solution, in crystals, and in gels (as determined by x-ray crys-
tallography, electron microscopy, and by infrared, ultraviolet-visible absorp-
tion, circular dichroic, NMR and EPR spectroscopy); (2) upon reactions: of
tetramers to form gels found in sickle cells, of subunits with each other, of
"oxidant drugs" with oxyHb, of ligands binding with metal, of anions,
organic phosphates, and other small molecules with protein, of iron(ll) to
give iron(lll), and of bound 0 to form Superoxide and peroxide; and (3) upon
2
cooperativity effects. A number of small molecules that retard gelation of
HbS and mixtures of HbS with other Hbs were reported. The erythrocyte
membrane and interactions between hemoglobin and membrane components
were discussed, with special emphasis on sickle cells. The criteria to which a
potential drug must conform, if it is to be clinically useful in the treatment
of sickle cell disease, were discussed, as were the functional abnormalities in
the red cell, whole blood, and elsewhere, that are associated with the
disease. Present methods for the evaluation of clinical severity in sickle cell
disease were also critically evaluated. Significant progress in research on the
properties and modes of formation of glycosylated hemoglobins was reported
and a promising new method for their determination for use in the evaluation
of diabetic conditions was discussed.
XIX