Table Of ContentMetabolism of Trace
Metals in Man
Volume II
Genetic Implications
Editors
Owen M. Rennert. M.D.
Wai-Yee Chan, Ph.D.
Department of Pediatrics
University of Oklahoma
Health Sciences Center
Oklahoma City, Oklahoma
First published 1984 by CRC Press
Taylor & Francis Group
6000 Broken Sound Parkway NW, Suite 300
Boca Raton, FL 33487-2742
Reissued 2018 by CRC Press
© 1984 by Taylor & Francis
CRC Press is an imprint of Taylor & Francis Group, an Informa business
No claim to original U.S. Government works
This book contains information obtained from authentic and highly regarded sources. Reasonable efforts have been
made to publish reliable data and information, but the author and publisher cannot assume responsibility for the
validity of all materials or the consequences of their use. The authors and publishers have attempted to trace the
copyright holders of all material reproduced in this publication and apologize to copyright holders if permission to
publish in this form has not been obtained. If any copyright material has not been acknowledged please write and
let us know so we may rectify in any future reprint.
Except as permitted under U.S. Copyright Law, no part of this book may be reprinted, reproduced, transmitted, or
utilized in any form by any electronic, mechanical, or other means, now known or hereafter invented, including
photocopying, microfilming, and recording, or in any information storage or retrieval system, without written
permission from the publishers.
For permission to photocopy or use material electronically from this work, please access www.copyright.com
(http://www.copyright.com/) or contact the Copyright Clearance Center, Inc. (CCC), 222 Rosewood Drive,
Danvers, MA 01923, 978-750-8400. CCC is a not-for-profit organiza-tion that provides licenses and registration
for a variety of users. For organizations that have been granted a photocopy license by the CCC, a separate system
of payment has been arranged.
Trademark Notice: Product or corporate names may be trademarks or registered trademarks, and are used only for
identification and explanation without intent to infringe.
A Library of Congress record exists under LC control number: 83002704
Publisher’s Note
The publisher has gone to great lengths to ensure the quality of this reprint but points out that some imperfections
in the original copies may be apparent.
Disclaimer
The publisher has made every effort to trace copyright holders and welcomes correspondence from those they have
been unable to contact.
ISBN 13: 978-1-138-50653-4 (hbk)
ISBN 13: 978-0-203-71135-4 (ebk)
Visit the Taylor & Francis Web site at http://www.taylorandfrancis.com and the CRC Press Web site at
http://www.crcpress.com
PREFACE
The importance of trace metals in human health and normal development is receiving
more and more attention. As a consequence of advancement in analytical techniques and
sophisticated instrumentation in the past two decades, there has been a rapid expansion in
biomedical research on trace elements. An increasing number of trace elements have been
found to be essential for life processes. Pronounced alterations in trace metal concentrations
in tissues or body fluids have been frequently observed in response to certain clinical
conditions such as infection, stress, malignant diseases, hormonal changes, etc. Changes in
trace metabolism during development are gradually being investigated and identified. Ter
atogenic effects of specific deficiency or excesses of trace metal are becoming an increasing
concern to developmental biologist and pediatricians. New human and animal mutants with
abnormal metal metabolism have been reported in recent years. The study of trace metals
no longer constitutes a small subdivision in nutrition. Its importance is significant to modern
nutritionists, biochemists, molecular biologists, developmental biologists, geneticists, en
vironmental scientists, pediatricians and other clinical disciplines.
A vast literature exists dealing with trace metals and a number of outstanding monographs
deal with the biological, biochemical, or clinical effects of a specific trace metal or trace
metals in general. However, newer aspects of trace metal research, i.e. the developmental
aspects and genetic implications, have not been systematically discussed in any existing
texts. The present two volumes will summarize the present status of research in these areas
and serve as milestones for future development in these areas of trace metal research.
THE EDITORS
Owen M. Rennert, M.D., is Professor and Head of the Department of Pediatrics,
Chief of the Section of Genetics, Endocrinology, and Metabolism, Professor, Depart
ment of Biochemistry and Molecular Biology, and Director of the Program in Human
Genetics in the Departments of Biochemistry and Molecular Biology and Pediatrics at
the University of Oklahoma Health Sciences Center, Oklahoma City. Dr. Rennert is
also Chief of the Pediatric Service of the Oklahoma Children’s Memorial Hospital,
Oklahoma City.
Dr. Rennert received his M.S. (Biochemistry) and M.D. from the University of Chi
cago. He completed his internship and residency and a postdoctoral fellowship in bio
chemistry at the University of Chicago as well.
During his military service, from 1964 to 1966, Dr. Rennert was a Senior Surgeon
with the U.S. Public Health Service and concurrently held the position of Research
and Clinical Associate at the NINDB, NIH, Section of Pediatric Neurology of the
Public Health Service, Bethesda, Maryland. Returning to the University of Chicago in
1966, Dr. Rennert worked as an Instructor and as Chief Resident (1966 to 1967) and
as an Assistant Professor (1967 to 1968) in the Department of Pediatrics. From 1968
to 1977, Dr. Rennert was on the faculty of the University of Florida College of Medi
cine, Gainesville, in the Departments of Pediatrics, Biochemistry, and Neuroscience,
and from 1970 to 1978 was Head of the Institutional Division of Genetics, Endocri
nology, and Metabolism and Director of the Sunland Training Center. Dr. Rennert
has been in his current position since 1977.
Dr. Rennert is active in numerous professional societies whose interests include clin
ical research, pediatrics, and biochemistry and has served as Chairman, Co-Chairman,
and Recorder at conferences of the Cystic Fibrosis Foundation, the American Associ
ation of Clinical Scientists, the Society for Pediatric Research, the American Pediatric
Society, and the Gordon Conference on Polyamines. He was Vice-President Elect of
the American Association of Clinical Scientists in 1980, and is currently on the Edito
rial Boards of the American Journal of Clinical Research and Annals of Clinical and
Laboratory Science.
Dr. Rennert has contributed to over 200 publications. His current research interests
include growth and differentiation in humans, the role of trace metals in growth and
differentiation, and the fundamental processes by which trace metals affect growth
and differentiation in humans.
Wai-Yee Chan, Ph.D., is an Associate Professor in the Department of Pediatrics
and the Department of Biochemistry and Molecular Biology at the University of Okla
homa Health Sciences Center, Oklahoma City. He is also Co-Scientific Director, Trace
Metals Laboratory of the State of Oklahoma Teaching Hospitals, and a Consultant in
Medical Service to the Veteran’s Administration Medical Center, Oklahoma City.
Dr. Chan received his B.Sc. with First Class Honors in Chemistry from the Chinese
University of Hong Kong. He received his Ph.D. in Biochemistry from the University
of Florida, Gainesville and was a Postdoctoral Fellow in Biochemistry at the University
of Oklahoma. Dr. Chan has been affiliated with the University of Oklahoma since
1977.
Dr. Chan is active in numerous professional societies whose interests include clinical
research, nutrition, biochemistry, and pediatrics. He is a national committee member
of the Council on Pediatrics and the Council on Trace Metals of the American College
of Nutrition. In recent years, Dr. Chan has been invited to participate in conferences
held by the Cystic Fibrosis Foundation, the NIH, Ross Laboratories, annd the Hospi
tal for Sick Children, Toronto, and has served as the American Delegate to the First
U.S.-China Bilateral Conference on Protein in Biology and Medicine and as Coordi-
nator to the Recent Advances in Protein Biochemistry Symposium sponsored by the
Chinese University of Hong Kong and the Hong Kong Biochemical Society.
Dr. Chan has contributed to numerous publications in his field of interest and has
presented papers to meetings of the American Society of Human Genetics, the Asso
ciation of Clinical Scientists, the American Pediatric Society, NATO ASI, the South
ern Society for Pediatric Research, and the American College of Nutrition. In addi
tion, he has conducted seminars at the University of Florida, the Oklahoma Medical
Research Foundation, the University of Oklahoma, the Shanghai Institute of Biochem
istry of the Chinese Academy of Science, Shanghai, and the Institute of Basic Medical
Science of the Chinese Academy of Medical Science, Beijing.
Dr. Chan’s research interests include trace element metabolism in development and
diseases, polyamine metabolism in animals, molecular mechanisms of genetic diseases
(Menke’s Disease, Wilson’s Disease, Cystic Fibrosis), lipoprotein metabolism in mam
mals, and lysosomal hydrolase metabolism.
CONTRIBUTORS
James M. Bates, Jr. M. Duane Enger, M.D.
Research Assistant II Deputy Division Leader
Department of Pediatrics Life Sciences Division
University of Oklahoma Health Sciences Los Alamos National Laboratory
Center University of California
Oklahoma City, Oklahoma Los Alamos, New Mexico
Michel Bourel, M.D. Lawrence C. Erway, Ph.D.
Professeur de Clinique Medicale Associate Professor
Hopital Pontchaillou Biological Sciences
Rennes, France University of Cincinnati
Cincinnati, Ohio
Wai-Yee Chan, Ph.D.
Associate Professor
J. K. Griffith, Ph.D.
Department of Pediatrics
Genetics Group
Department of Biochemistry and Molecu
Los Alamos National Laboratory
lar Biology
University of California
University of Oklahoma Health Sciences
Los Alamos, New Mexico
Center
Co-Scientific Director
Jack Hegenauer, Ph.D.
Trace Metals Laboratory
Associate Research Biologist
State of Oklahoma Teaching Hospitals
Department of Biology
and
University of California at San Diego
Consultant
La Jolla, California
Medical Service
Veteran’s Administration Medical Center
C. E. Hildebrand, Ph.D.
Oklahoma City, Oklahoma
Deputy Group Leader
Genetics Group
David L. Donaldson, M.D.
Los Alamos National Laboratory
Assistant Professor
University of California
Department of Pediatrics
Los Alamos, New Mexico
University of Oklahoma
Health Sciences Center
Nina Horn, Ph.D.
Oklahoma Children’s Memorial Hospital
Department of Medical Genetics
State of Oklahoma Teaching Hospitals
John F. Kennedy Institute
Oklahoma City, Oklahoma
Glostrup, Denmark
Gunther L. Eichhorn, Ph.D.
Chief, Laboratory of Cellular and Molec Jeng M. Hsu, Ph.D., D.V.M.
ular Biology Medical Research Service
Chief, Inorganic Biochemistry Section Veterans Administration Medical Center
Bay Pines, Florida
Roland M. Leach, Jr., Ph.D.
Professor of Poultry Science Leslie M. Klevay, M.D.,
The Pennsylvania State University Sc.D.(Hygeine)
University Park, Pennsylvania Research Medical Officer
National Institutes of Health Research Leader
National Institute on Aging USDA-ARS Human Nutrition Research
Gerontology Research Center Center
Baltimore, Maryland Grand Forks, North Dakota
Max Perlman. M.D. Owen M. Rennert, M.D.
Clinical Director Professor and Head, Department of
Neonatal Division Pediatrics
Hospital for Sick Children Professor, Department of Molecular Biol
Associate Professor ogy and Biochemistry
Department of Pediatrics Head, Division of Genetics, Endocrinol
University of Toronto ogy, and Metabolism
Toronto, Ontario, Canada University of Oklahoma Health Sciences
Center
Ananda S. Prasad, M.D., Ph.D. Chief, Pediatric Services
Professor of Medicine Oklahoma Children’s Memorial Hospital
Director, Division of Hematology State of Oklahoma Teaching Hospitals
Wayne State University School of Oklahoma City, Oklahoma
Medicine
Chief of Hematology
Harper-Grace Hospitals Paul Saltman, Ph.D.
Detroit, Michigan Professor
and Department of Biology
Veterans Administration Medical Center University of California at San Diego
Allen Park, Michigan La Jolla, California
D. Cristina Sarale, M.D.
Department of Pediatrics
University of Oklahoma Health Sciences
Center
Oklahoma Children’s Memorial Hospital
State of Oklahoma Teaching Hospitals
Oklahoma City, Oklahoma
TABLE OF CONTENTS
Volume I
Chapter 1
For The Want of a Nail...Trace Elements in Health and Disease........................................ 1
P. Saltman, J. Hegenauer, and L. Strause
Chapter 2
Genetic and Developmental Implications for Trace Metal Metabolism from Mutant and
Inbred Strains of Animals.........................................................................................................17
L. C. Erway
Chapter 3
Perinatal Aspects of Trace Metal Metabolism.......................................................................51
M. Perlman
Chapter 4
Trace Elements in Human Milk...............................................................................................63
W.-Y. Chan, J. M. Bates, Jr., and O. M. Rennert
Chapter 5
Trace Metals in Growth and Sexual Maturation....................................................................79
A. S. Prasad
Chapter 6
Homeostasis of Trace Elements in the Aged.........................................................................99
A. A. Yunice and J. M. Hsu
Chapter 7
The Role of Copper, Zinc, and Other Chemical Elements in Ischemic Heart Disease.. 129
L. M. Klevay
Index............................................................................................................................................159
Volume II
Chapter 1
Introduction: Metal Ions and Genetic Regulation.................................................................... 1
G. L. Eichhorn
Chapter 2
Molecular and Somatic Cell Genetics Analysis of Metal Metabolism in Cultured Cells .. 7
M. D. Enger, C. E. Hilderbrand, J. K. Griffith, and R. A. Walters
Chapter 3
Copper Metabolism in Menke’s Disease...................................................................................25
N. Horn
Chapter 4
Wilson’s Disease: Recent Advances.........................................................................................53
D. C. Sarale, W.-Y. Chan, and O. M. Rennert
Chapter 5
Acrodermatitis Enteropathica: Pathogenesis and Implications for Treatment 71
P. A. Walravens
Chapter 6
Clinical and Biochemical Studies of Idiopathic Hemochromatosis.......................................81
M. Simon and M. Bourel
Chapter 7
Genetic Aspects of Manganese Metabolism..........................................................................109
R. M. Leach
Chapter 8
Trace Elements and Diabetes Mellitus....................................................................................113
D. L. Donaldson and O. M. Rennert
Chapter 9
Genetic Diseases: Models for the Study of Trace Metals..................................................133
O. M. Rennert and W.-Y. Chan
Index............................................................................................................................................141
