COPPER BIOAVAILABILITY AND ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY Editorial Board: NATHAN BACK, State University of New York at Buffalo IRUN R. COHEN, The Weizmann Institute of Science DAVID KRITCHEVSKY, Wistar Institute ABEL LAJTHA, N. S. Kline Institute for Psychiatric Research RODOLFO PAOLETTI, University of Milan

Recent Volumes in this Series

Volume 252 DRUGS, SYSTEMIC DISEASES, AND THE KIDNEY Edited by Alberto Amerio, Pasquale Coratelli, Vito M. Campese, and Shaul G. Massry

Volume 253A PURINE AND PYRIMIDINE METABOLISM IN MAN VI, Part A: Clinical and Molecular Biology Edited by Kiyonobu Mikanagi, Kusuki Nishioka, and William N. Kelley

Volume 253B PURINE AND PYRIMIDINE METABOLISM IN MAN VI, Part B: Basic Research and Experimental Biology Edited by Kiyonobu Mikanagi, Kusuki Nishioka, and William N. Kelley

Volume 254 MECHANISMS OF LYMPHOCYTE ACTIVATION AND IMMUNE REGULATION II Edited by Sudhir Gupta and William E. Paul

Volume 255 CALCIUM SIGNALING Edited by H. Hidaka

Volume 256 ENDOTOXIN Edited by Herman Friedman, T. W. Klein, Masayasu Nakano, and Alois Nowotny

Volume 257 THE IMMUNE RESPONSE TO VIRAL INFECTIONS Edited by B. A. Askonas, B. Moss, G. Torrigiani, and S. Gorini

Volume 258 COPPER BIOA VAILABILITY AND METABOLISM Edited by Constance Kies

Volume 259 RENAL EICOSANOIDS Edited by Michael J. Dunn, Carlo Patrono, and Giulio A. Cinotti

A Continuation Order Plan is available for this series. A continuation order will bring delivery of each new volume immediately upon publication. Volumes are billed only upon actual shipment. For further information please contact the publisher. COPPER BIOAVAILABILITY AND METABOLISM

Edited by Constance Kies University of Nebraska Lincoln, Nebraska

PLENUM PRESS • NEW YORK AND LONDON Library of Congress Cataloging in Publication Data

American Chemical Society Symposium on Copper Bioavailability and Metabolism (1989: Dallas, Tex.) Copper bioavailability and metabolism / edited by Constance Kies. p. cm. - (Advances in experimental medicine and biology; v. 258) "Proceedings of the American Chemical Society Symposium on Copper Bioavailabili- ty and Metabolism, held April 9-14, 1989, in Dallas, Texas" - Verso of Lp. Includes bibliographical references. ISBN -13 :978-1-4612-7855-9 e-ISBN -13 :978-1-4613-0537-8 DOl: 10.1007/978-1-4613-0537-8

I. Copper - Bioavailability -Congresses. 2. Copper - Metabolism - Congresses. I. Kies, Constance. II. Title. III. Series. QP535.C9A44 1989 89-22994 612.3'924-dc20 CIP

Proceedings of the American Chemical Society Symposium on Copper Bioavailability and Metabolism, held April 9-14, 1989, in Dallas, Texas © 1989 Plenum Press, New York Softcover reprint of the hardcover 1st edition 1989

A Division of Plenum Publishing Corporation 233 Spring Street, New York, N.Y. 10013 All rights reserved No part of this book may be reproduced, stored in a retrieval system, or transmitted in any form or by any means, electronic, mechanical, photocopying, microfilming, recording, or otherwise, without written permission from the Publisher PREFACE

Nutrition is truly a science of the 20th century. That physiological disabilities could be caused by a lack of exogenous substances which could be supplied by foods is a concept of relatively recent origins.

It is not surprising, therefore, that, until the last few years, much of nutritional science research was tied to: 1) establishing a cause and effect relationship between a physiological problem and its cure/prevention by a chemical substance in food; 2) quantifying the amount of the substance (nutrient) needed to prevent deficiency symptoms; and 3) quantifying the amounts of nutrients found in various food substances.

That a nutrient might be present in apparently adequate amounts in foods consumed by an individual but could not be fully utilized because of the concurrent consumption of anti-nutrients has been recognized as being an important problem as, for example, iodine-deficiency goiters resulting from consumption of gOitrigens. That less specific, less dramatic interactions among nutrients and among nutrients and other food components might enhance or inhibit the absorption of nutrients from the intestines or of the metabolism of nutrients within the body is an area of current concern.

The Agriculture and Food Chemistry Division of the American Chemical Society in recognition of the importance of bioavailability, bioutilization and metabolism of mineral nutrients has been sponsoring a series of symposiums with the objective of bringing together established research scientists and investigators at the start of their careers. By so doing, current information can be defined and future research directions can be illustrated. This volume is the result, in large part, of the efforts of the participants of the most recent of these symposiums, i.e. Bioavailability and Metabolism of Copper.

The editor would like to thank Mrs. Donna Hahn for her efforts in helping to organize the American Chemical Society symposium in which the oral versions of many of the chapters included in this book were first presented as well as her technical assistance making this volume become a reality.

Constance Kies Editor

v CONTENTS

Introduction ...... • • ...... • • • • • • • • • • • • • •• xi

COPPER IN FOODS AND FACTORS AFFECTING ITS AVAILABILITY

Food Sources of Dietary Copper C. Kies

Stable Isotope Studies of the Effect of Dietary Copper on Copper Absorption and Excretion • . • • • • • 21 J.R. Turnlund

Influence of Ascorbic Acid, , Iron, Sucrose and Fructose on Copper Status ...... • . 29 M.A. Johnson

Copper Absorption as Affected by Supplemental Calcium, , Manganese, and Potassium • • 45 C. Kies and J.M. Harms

The Type of Dietary Carbohydrate Consumed During Pregnancy and Lactation Determines Copper Status of the Fetus and the Neonate Rat • . . . • • • . . . . 59 M. Fields, C.G. Lewis and T. Beal

Factors Affecting Copper Absorption in Humans and Animals 71 P.E. Johnson

Inhibitors of Copper Bioutilization: Fiber, Lead, Phytate and • • • . • 81 C. Kies and J. Umoren

COPPER ABSORPTION AND TRANSPORT

Copper Transport: Insights into a Ceruloplasmin-Based Delivery System • • • . • • • • • • • • . • • • 95 E.D. Harris and S.S. Percival

The Biodistribution of Radiocopper-Labeled Compounds . . . . • • . • • 103 J.A. Mercer-Smith, D.A. Cole, J.C. Roberts, D. Lewis, M.J. Behr and D.K. Lavallee

vii Metalloforms of Metallothionein Induced by Parenteral Copper: The Influence of Route of Administration • • • • • • • • • • • • 123 C.C. McCormick, L.-Y. Lin and J.C. Fleet

Mechanism of Copper Transport and Delivery in Mammals: Review and Recent Findings • • •• •••••••••••.•• 131 C.A. Goode, C.T. Dinh and M.C. Linder

COPPER METABOLISM AND PHYSIOLOGICAL EFFECTS

Copper and Zinc Status in Moderate Alcohol Intake ••••. 145 N.A. Frimpong and J. Louis-Charles

Effect of Estrogen on Serum and Tissue Levels of Copper and Zinc . • • 155 S.W. Mehta and R. Eikum

Effects of Exercise Training on Human Copper and Zinc Nutriture . • • 163 H.C. Lukaski

Serum Total Cholesterol and HDL-Cholesterol Levels as Associated with Copper and Zinc Intake in Physically Active And Sedentary Elderly Men and Women •••.•.••...••••• 171 J. Umoren

Modulation of Long Chain Fatty Acid Unsaturation by Dietary Copper • • 183 S.C. Cunnane

Ischemic Heart Disease as Copper Deficiency • . • • • • • • • • • • • 197 L.M. Klevay

Copper Complexes Stimulate Hemopoiesis and Lymphopoiesis . . • . . • . 209 L.S.F. Soderberg, J.B. Barnett and L.R.J. Sorenson

Exocrine Pancreatic Function of Rats Consuming a High-Fructose, Low-Copper Diet • • • •• •.•••••.••. 219 C.G. Lewis and M. Fields

Bioavailable Copper Complexes Offer a Physiologic Approach to Treatment of Chronic Diseases . • . • . • . •• .••••• 229 J.R.J. Sorenson, S.F. Soderberg, M.V. Chidambaram, D.T. de la Rosa, H. Salari, K. Bond, G.L. Kearns, R.A. Gray, C.E. Epperson and M.L. Baker

Changes in Serum Copper and Zinc During Treatment with Anticancer Drugs Interfering with Pyridoxal Phosphate • • • • . 235 M. Slavik, T.R. Narasimhan, C. Riley and J. Slavik

Effect of Copper on Immune'Function and Disease Resistance ..•••• 243 J.R. Stabel and J.W. Spears

Effects of Inflammation on Copper Antioxidant Enzyme Levels • . • . • 253 R.A. DiSilvestro

Copper-67 Labeled Porphyrin Localization in Inflamed Tissues • . • . • 259 D.A. Cole, J.A. Mercer-Smith, J.K. Norman, S.A. Schreyer, K.P. Bullington, J.C. Roberts and D.K. Lavallee

Serum Copper Concentration as an Index of Clinical Lung Injury . • • • 273 A. Molteni, W.F. Ward, Y.T. Kim, R. Shetty, L. Brizio-Molteni, R. Giura, H. Ribner and M. Lomont

viii Serum Copper Concentration as an Index of Experimental Lung Injury • • • • • • • • • • • • • • • • • • . • • • • • • • • 287 W.F. Ward, A. Molteni, C. Ts'ao and H. Ischiropoulos

Index ••••••••••••••••.•••.••••••.••••• 303 INTRODUCTION

Constance Kies

Department of Human and Food Service Management University of Nebraska Lincoln, NE

The usefulness of copper to people dates back to antiquity (Adriano, 1986). It was one of the first metals used by humans. The discovery of hardening of copper by alloying it with tin to form bronze marked the end of the stone age. Currently, about half of the world production of copper is used in electrical equipment but its alloys are used in plumbing, piping and a wide variety of other products. In addition, copper compounds are used as fungicides and herbicides, insecticides and bactericides, preservatives, pigments in paints and ceramics, algicides, food and feed additives and fertilizers (Adriano, 1986; Kutsky, 1981).

Recognition of the biological importance of copper is of recent origins (Kutsky, 1981). In 1830, Bucholz identified copper in plants. That copper occurs in animal tissue was recognized somewhat later by such investigators as Frederick in 1878 who reported the presence of copper in hemocyanin and by Brodansky who, in 1921, identifed copper in human brain. Not until 1928 did Hart and co-workers establish that copper is an essential nutrient for animals.

Provision of adequate copper nutrition is now known or suspected to be vital in normal functioning and maintenance of a large number of body systems including circulatory, excretory, respiratory, digestive, nervous special sensory, endocrine, metabolic and reproductive. These basic understandings have been reviewed by O'Dell (1984), Davis and Mertz (1986), Owen (1982) and Solomons (1988). Several chapters in this book are devoted to the most current research relative to the physiological functions of copper.

Dietary, environmental and genetic causes may result in symptoms of copper deficiency or copper toxicity (Owen, 1981; Davis and Mertz, 1986; Carson, 1987). Menke's syndrome is a genetic defect caused condition which results in defective copper absorption and copper deficiency while Wilson's disease, another inborn error of metabolism, results in copper toxicity due to defective copper excretion in bile. Normally in humans copper is absorbed in the stomach and duodenum and is transported as copper-protein complexes. Current theories of mechanisms of copper absorption have been reviewed by Davis and Mertz (1986), Solomons (1988) and Owen (1982) in this volume. Bile is the principal route of endogenous copper excretion in the human.

Foods vary in their copper contents. Because much of the information on copper concentration in foods commonly eaten in the United States is scattered, food composition tables relative to copper have been included. Copper may be present in food but its absorption and utilization may be influenced by a large number of dietary and non-dietary factors (Owen, 1981; 1982). Among the dietary factors influencing copper bioutilization are protein and amino acids, sugars, fiber, minerals (nutritionally-essential, non• essential, and suspected toxic elements), ascorbic acid, and other vitamins, phytates and tannins. In addition, physiological states including growth, aging, pregnancy and lactation, and exercise may result in altered need and utilization of copper. Pharmaceutical products may change physiological utilization and need for copper. Many of these factors are discussed in detail in this volume.

Current methodology now allows for greater, more precise definition of copper involvement in human metabolism. Although a primary purpose of this volume is not to present methodological procedures per se, all chapters have been written by individuals who are currently active in copper nutrition/biochemical/physiological research. By so doing, what is currently being done and what can be done now is presented.

REFERENCES

Adriano, D.C. Trace Elements in the Terrestrial Environment. Springer-Verlag: New York, NY, 1986, pp. 181-218.

Carson, B.L., Ellis, H.V. III, and McCann, J.L. Toxicological and Biological Monitoring of Metals in Humans. Lewis Publishing Co.: Chelsea, MI, 1987, pp. 93-98.

Davis, G. and Mertz, W. Copper. In: Trace Elements in Human and Animal Nutrition, 5th ed., W. Mertz, ed. Academic Press: San Diego, CA, 1986, pp. 301-364.

Kutsky, R.J. Handbook of Vitamins, Minerals and Hormones, 2nd ed. Van Nostrand Reinhold Co.: New York, NY, 1981, pp. 101-112.

O'Dell, B.L. Copper. In: Present Knowledge in Nutrition, 5th ed. Nutrition Foundation: Washington, DC, 1984, pp. 506-518.

Owen, C.A. Copper deficiency and toxicity. In: Copper in Biology and Medicine Series. Noyes Publishing: Park Ridge, NJ, 1981, 189 p.

Owen, C.A. Biochemical aspects of copper. In: Copper in Biology and Medicine Series. Noyes Publishing: Park Ridge, NJ, 1982, 206 p.

Owen, C.A. Biological aspects of copper. In: Copper in Biology and Medicine Series. Noyes Publishing: Park Ridge, NJ, 1982, 138 p.

Owen, C.A. Physiological aspects of copper. In: Copper in Biology and Medicine Series. Noyes Publishing: Park Ridge, NY, 1982, 286 p.

Solomons, N.W. Zinc and copper. In: Modern Nutrition in Health and Disease, Shils, M.E. and Young, V.R., eds. Lea and Febiger: Philadelphia, PA, 1988, pp. 238-262.