Table Of ContentContributors
Allen C. Alfrey Tord Kjellström
Norman Aspin Ismael Mena
Malcolm Cox Harold H. Sandstead
Lars Friberg Andrew Sass-Kortsak
Robert A. Goyer Irwin Singer
K. Michael Hambidge Frank A. Smith
Harold C. Hodge F. William Sunderman, Jr.
A. Jacobs Paul W. Winston
M. Worwood
Disorders of
Mineral Metabolism
VOLUME I
Trace Minerals
Edited by
FELIX BRONNER
Department of Oral Biology
School of Dental Medicine
University of Connecticut Health Center
Farmington, Connecticut
JACK W. COBURN
Medical and Research Services
V. A. Wadsworth Medical Center, and
Department of Medicine
UCLA School of Medicine
Los Angeles, California
1981
ACADEMIC PRESS
A Subsidiary of H ar court Brace Jovanovich, Publishers
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COPYRIGHT © 1981, BY ACADEMIC PRESS, INC.
ALL RIGHTS RESERVED.
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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:
Disorders of mineral metabolism.
Includes index.
Contents: v. 1. Trace minerals.
1. Mineral metabolism disorders. I. Bronner, Felix.
II. Coburn, J. W., Date. [DNLM: 1. Metabolism,
Inborn errors. 2. Minerals—Metabolism.
WD 205.5.MA D612]
RC632.M56D57 616.3'99 80-2761
ISBN 0-12-135301-X (vol. 1) AACR2
PRINTED IN THE UNITED STATES OF AMERICA
81 82 83 84 9 8 7 6 5 4 3 2 1
List of Contributors
Numbers in parentheses indicate the pages on which the authors' contributions begin.
Allen C. Alfrey (353), Veterans Administration Hospital, Denver, Colorado
80220
Norman Aspin* (59), Research Institute, University of Toronto Hospital for
Sick Children, Toronto, Ontario M5G 1X8, Canada
Malcolm Cox (369), Medical Service, Veterans Administration Medical Center,
Philadelphia, Pennsylvania, and Renal-Electrolyte Section, Department of
Medicine, University of Pennsylvania School of Medicine, Philadelphia,
Pennsylvania 19104
Lars Friberg (317), Department of Environmental Hygiene, The Karolinska
Institute, and The National Institute of Environmental Medicine, Stockholm,
Sweden
Robert A. Goyer (159), National Institute of Environmental Health Sciences,
Research Triangle Park, North Carolina 27709
K. Michael Hambidge (271), Department of Pediatrics, University of Colorado
Medical Center, Denver, Colorado 80220
♦Present address: Canadian Nuclear Association, 111 Elizabeth Street, Toronto, Ontario M5G
1P7, Canada
xi
XII List of Contributors
Harold C. Hodge (439), Department of Pharmacology, School of Medicine,
University of California-San Francisco, San Francisco, California 94143
A. Jacobs (1), Welsh National School of Medicine, Heath Park, Cardiff CF4
4XN, Wales, United Kingdom
Tord Kjellström (317), Department of Community Health, University of
Auckland, Auckland, New Zealand
Ismael Mena (233), Division of Nuclear Medicine, LAC Harbor-UCLA Medical
Center, Torrance, California 90509
Harold H. Sandstead (93), United States Department of Agriculture, Science and
Education Administration, Human Nutrition, Grand Forks Human Nutrition
Research Center, Grand Forks, North Dakota 48202
Andrew Sass-Kortsak (59), Department of Paediatrics, University of Toronto
Hospital for Sick Children, Toronto, Ontario M5G 1X8, Canada
Irwin Singer (369), Medical Service, Veterans Administration Medical Center,
Philadelphia, Pennsylvania, and Department of Medicine, University of
Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104
Frank A. Smith (439), Department of Radiation Biology and Biophysics,
University of Rochester School of Medicine and Dentistry, Rochester, New
York 14642
F. William Sunderman, Jr. (201), Department of Laboratory Medicine,
University of Connecticut Health Center, Farmington, Connecticut 06032
Paul W. Winston (295), Department of Environmental, Population and
Organismic Biology, University of Colorado, Boulder, Colorado 80309
M. Worwood (1), Department of Haematology, Welsh National School of
Medicine, Heath Park, Cardiff CF4 4XN, Wales, United Kingdom
Preface
k Disorders of Mineral Metabolism' ' is intended as a comprehensive, up-to-date
treatise on the pathophysiology of calcium, phosphorus, and magnesium and of
other clinically relevant minerals and elements, such as iron, copper, zinc,
fluoride, and the like.
Recent years have seen major advances in our understanding of how these
minerals function in the mammalian body and why they are important in
medicine. Thus the failure to provide adequate concentrations of calcium in
hemodialysis fluids or to regulate their fluoride or aluminum concentrations may
lead to severe bone disease of patients who are being maintained on dialysis.
Understanding of the metabolism of vitamin D has underscored the pivotal role
played by renal tissue in providing the body with an adequate supply of 1,25-
dihydroxyvitamin D , the metabolite active in the intestinal cell and modulating
3
one component of calcium absorption. Indeed, what characterizes current under-
standing is the appreciation of what may at first appear to be remote control
loops as in the role played by the vitamin D-regulated component of bone
metabolism in the body handling of the cadmium.
It therefore seems entirely fitting that this treatise unites what appear to be
disparate subjects whose detailed understanding differs widely. It is the editors'
hope that knowledge gained in one area may serve to stimulate research in
another. An example is the high intracellular concentration of magnesium whose
regulation and relationship to extracellular magnesium are not understood. The
total intracellular calcium is low and the intracellular free calcium concentration
is carefully regulated at between 10-7 and 10~6 M. This appears to involve
XIII
XIV Preface
complicated interactions between various cellular organelles, all of which have
calcium-binding proteins with an association constant of about 106 M_1. Yet
extracellular calcium is also closely regulated at 10"3 M, and the body expends
considerable energy in the regulation of both intra- and extracellular calcium.
How are these two related and could intra- and extracellular calcium regulation
serve as a model for understanding the regulation of magnesium? Such questions
could be multiplied manyfold. We hope this treatise will not only serve as a
useful reference, but stimulate readers to reflect on parallels and distinctions
between subjects.
Volume I of the treatise deals with minerals and elements whose average daily
intake is under 50 mg. They are therefore conveniently termed "trace elements. "
While many are essential for life, the essentiality of others has not been estab-
lished. Inclusion was largely a matter of clinical interest and relevance.
Volume II deals with the normal function of calcium, knowledge of which has
exploded in recent years, with much emphasis on a host of intracellular
functions. These have been summarized in the first chapter. In the remainder of
the volume, calcium absorption, excretion, and homeostasis are discussed in
detail, along with the hormonal modifiers of its metabolism. The role of connec-
tive tissue and bone, the major storehouse of body calcium, is reviewed in terms
of collagen metabolism.
Volume III deals with the pathophysiology of calcium in bone and kidney and
their disorders, along with detailed consideration of phosphate and magnesium
metabolism. Throughout this and the other volumes the viewpoint has been that
of disorders and how they arise; therapy has been discussed in terms of principles
rather than from the viewpoint of specific management.
This treatise was inspired by a desire to bring up-to-date the earlier one on ' 'Min-
eral Metabolism" edited by C. L. Comar and Felix Bronner. It became apparent
early that comprehensive updating and expansion were no longer possible. An ex-
ample is the Na+-K + ATPase, mentioned in a footnote in the earlier treatise, which
could now easily command its own volume. Similar comments apply to iodine
and the thyroid diseases, to the electrolytes Na+ and K+ and their diseases, and a
host of other subjects. Not only has there been an expansion of knowledge, the
approach has changed, with much greater emphasis on an understanding of the
molecular basis of many events. Some subjects have not advanced as much as
others. This applies in particular to the relationship between events at the cellu-
lar, tissue, and organism levels. Just as true understanding of a mechanism
requires reconstitution experiments, so appreciation of the disease process ulti-
mately demands integration of events at all levels of organization, from the
molecular to the whole organism. While this treatise makes halting steps in that
direction, we hope future research will bring us closer to that goal.
Felix Bronner
Jack W. Coburn
Contents of Other Volumes
VOLUME II
Calcium Physiology
1. The Regulation of the Cellular Functions of Ca2+
Ernesto Carafoli
2. Calcium Homeostatis
Felix Bronner
3. Intestinal Absorption of Calcium: Its Assessment, Normal
Physiology, and Alterations in Various Disease States
Barton S. Levine, Marlin W. Walling, and Jack W. Coburn
4. Renal Handling of Calcium
S haul G. Massry
5. Collagen Biosynthesis and Degradation
Marvin L. Tänzer
6. Parathyroid Hormone
Jan A. Fischer
7. Vitamin D: Metabolism, Actions, and Disease States
Mark R. Haus s 1er and Arnold S. Brickman
8. Calcitonin Secretion
Leonard J. Deftos
9. Hormonal Modifiers of Mineral Metabolism Other than
Parathyroid Hormone, Vitamin D, and Calcitonin
Robert K. Rude and Frederick R. Singer
XV
XVI Contents of Other Volumes
VOLUME III
Pathophysiology of Calcium, Phosphorus, and Magnesium
1. Disorders of Bone Resorption
G. Mundy and L. Raisz
2. Osteoporosis
R. Heaney
3. Calcium Nephrolithiasis
C. Pak
4. Calcium Metabolism in Renal Failure
E. Ritz, H. H. Malluche, B. Krempien, and O. Mehls
5. Parathyroid Hormone, Acid-Base Balance, and Calcium
Metabolism: Interrelations and Interactions
Uriel S. Barzel
6. Disorders of Phosphorus Metabolism
David B. N. Lee, Nachman Brautbar, and Charles R. Kleeman
7. Magnesium Metabolism
Constantine S. Anast and David W. Gardner
1
Iron
A. Jacobs and M. Worwood
I. Inorganic Biochemistry 2
II. Iron-Containing Proteins 2
A. Hemoproteins 4
B. Non-Heme Iron-Containing Enzymes 4
C. Transferrin and Lactoferrin 4
D. Ferritin and Hemosiderin 6
E. Iron-Dependent Enzymes 9
III. Iron Absorption 9
A. Release of Iron from Food 9
B. Iron Transport within the Intestinal Epithelial Cell 10
C. Regulation of Iron Absorption 10
IV. Internal Metabolism 11
A. The Iron Content of the Body 11
B. Plasma Iron Kinetics 13
C. Iron Uptake by Transferrin 13
D. Cellular Uptake of Transferrin-Bound Iron 14
E. Intracellular Iron Metabolism 15
V. Methods Used for Clinical Investigation 18
A. Serum Iron and Total Iron-Binding Capacity (TIBC) 18
B. Serum Ferritin 19
C. Chelating Agents 21
D. The Direct Measurement of Storage and Tissue Iron 21
E. Erythrocyte Changes 22
F. Ferrokinetics 22
VI. Iron Deficiency 23
A. Etiology 23
B. Erythropoiesis 26
C. Nonerythroid Tissue 27
D. Iron and Infection 28
Disorders of Mineral Metabolism, Vol. I
Copyright © 1981 by Academic Press, Inc.
All rights of reproduction in any form reserved.
ISBN 0-12-135301-X
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