Biochemistry of the Essential Ultratrace Elements OF THE ELEMENTS Series Editor: Earl Frieden Florida State University Tallahassee, Florida

Volume 1 BIOCHEMISTRY OF NONHEME Anatoly Bezkorovainy Volume 2 BIOCHEMISTRY OF Raymond J. Shamberger Volume 3 BIOCHEMISTRY OF THE ESSENTIAL ULTRATRACE ELEMENTS Edited by Earl Frieden

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. Biochemistry of the Essential Ultratrace Elements

Edited by Earl Frieden The Florida State University Tallahasse, Florida

PLENUM PRESS • NEW YORK AND LONDON Library of Congress Cataloging in Publication Data Main entry under title: Biochemistry of the essential ultratrace elements. (Biochemistry of the elements; v. 3) Bibliography: p. Includes index. 1. Trace elements-. 2. Trace elements in the body. 3. Biological chemistry. I. Frieden, Earl. II. Series. QP534.B54 1984 574.1'9214 84-17973 ISBN-13: 978-1-4684-4777-4 e-ISBN-13: 978-1-4684-4775-0 DOl: 10.1007/978-1-4684-4775-0

© 1984 Plenum Press, New York Softcover reprint of the hardcover 1st edition 1984 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 Contributors

Nicholas M. Alexander • Division of Clinical Pathology, Department of Pa• thology, University of California School of Medicine, San Diego, California 92103 Richard A. Anderson • Beltsville Research Center, U.S. Department of Agriculture, Beltsville, Maryland 20705 Janet S. Borel • Beltsville Human Nutrition Research Center, U.S. Depart• ment of Agriculture, Beltsville, Maryland 20705 EdithM. Carlisle • Division of Nutrition, School of Public Health, University of California, Los Angeles, California 90024 W. M. Dugger • Department of Botany and Plant Sciences, University of California, Riverside, California 92521 Earl Frieden • Department of Chemistry, Florida State University, Tallahas• see, Florida 32306 LeonL. Hopkins • Department of Food and Nutrition, Texas Tech University, Lubbock, Texas 79409 Lucille S. Hurley • Department of Nutrition, University of California, Davis, California 95616 Carl L. Keen • Department of Nutrition, University of California, Davis, California 95616 M. Kirchgessner • Institute of Nutrition Physiology, Technical University Miinchen D-8050 Freising-Weihenstephan, F.R.G. Bo Lonnerdal • Department of Nutrition, University of California, Davis, California 95616 Carol Lovatt • Department of Botany and Plant Sciences, University of Cal• ifornia, Riverside, California 92521 Harold H. Messer • Department of Oral Biology, University of Minnesota, Minneapolis, Minnesota 55455 David B. Milne • U.S. Department of Agriculture, Agricultural Research Service, Grand Forks Human Nutrition Research Center, Grand Forks, North Dakota 58202

v vi Contributors

Forrest H. Neilsen • U.S. Department of Agriculture, Agricultural Research Service, Grand Forks Human Nutrition Research Center, and Department of Biochemistry, University of North Dakota, Grand Forks, North Dakota 58202 K. V. Rajagopalan • Department of Biochemistry, Duke University Medical Center, Durham, North Carolina 27710 A. M. Reichlmayr-Lais • Institute of Nutrition Physiology, Technical Uni• versity Munchen D-8050 Freising-Weihenstephan, West Germany Gerhard N. Schrauzer • Department of Chemistry, University of California at San Diego, La Jolla, California 92093 RaymondJ. Shamberger • The Cleveland Clinic, 9500 Euclid Avenue, Cleve• land, Ohio 44106 Harry A. Smith • Department of Chemistry, Florida State University, Tal• lahassee, Florida 32306 Barbara J. Stoecker • Department of Food and Nutrition, Texas Tech Uni• versity, Lubbock, Texas 79409 Eric O. Uthus • U.S. Department of Agriculture, Agricultural Research Ser• vice, Grand Forks Human Nutrition Research Center and Department of Biochemistry, University of North Dakota, Grand Forks, North Dakota 58202 Roland S. Young • Consulting Chemical Engineer, 605, 1178 Beach Drive, Victoria, B.C. V8S 2M9, Canada Preface

The remarkable development of molecular biology has had its counterpart in an impressive growth of a segment of biology that might be described as atomic biology. The past several decades have witnessed an explosive growth in our knowledge of the many elements that are essential for life and maintenance of plants and animals. These essential elements include the bulk elements (hydro• gen, carbon, nitrogen, oxygen, and ), the macrominerals (, potas• sium, , , chloride, and ), and the trace elements. This last group includes the ultra trace elements and iron, , and . Only the ultratrace elements are featured in this book. Iron has attracted so much research that two volumes are devoted to this metal-The Biochemistry ofNon-Heme Iron by A. Bezkoravainy, Plenum Press, 1980, and The Biochemistry of Heme Iron (in preparation). Copper and zinc are also represented by a separate volume in this series. The present volume begins with a discussion of essentiality as applied to the elements and a survey of the entire spectrum of possible required elements. This is followed by an outline of the history of the research on trace elements that led to their identification as essential. Each of the remaining chapters is devoted to an essential ultratrace element and is written by an expert on that particular element. Individual chapters include , , manganese, co• balt, , molybdenum, selenium, , , nickel, boron, ar• senic, , , and . The inclusion of the last several elements may represent a premature designation as essential. Nonetheless, a separate indepen• dent chapter for each of these elements should be useful, if only because of the extensive research now in progress. This text hopes to bring together our present knowledge of the essential ultratrace elements and to serve as a guide to further biochemical research on these elements and others not yet so designated.

EARL FRIEDEN Professor of Chemistry Florida State University Tallahassee, Florida

vii Contents

1. A Survey of the Essential Biochemical Elements 1 Earl Frieden 1.1 Essentiality 1.1.1 Stimulatory Metals 3 1.1.2 Evolution of the Essential Trace Elements 4 1.2 A Survey of the Biochemistry of the Elements 5 1.2.1 The Nonmetals: 8 1.2.2 The Metals 9 1.2.3 Pretransition Metals 9 1.2.4 The Alkali Metals; , Rubidium 9 1.2.5 The Alkaline Earth Metals; Beryllium, Strontium, Barium 11 1.2.6 Remaining Pre-transition Metals 11 1.2.7 The Transition Metals 11 1.2.8 The Post-transition Metals 12 1.2.9 Lanthanides and Actinides 13 1.3 Mechanism of Action of the Essential Ultratrace Elements 13 1.4 Summary 14 General References 15 Specific References 15

2. The Discovery of the Essential Trace Elements: An Outline of the History of Biological Trace Element Research 17 Gerhard N. Schrauzer 2.1 Introduction 17 2.2 Classification of the Bioelements 18 2.3 The Concept of Essentiality 19

ix x Contents

2.4 Trace Element Discoveries from 1925 to 1956 20 2.4.1 Copper 20 2.4.2 Manganese 20 2.4.3 Zinc 21 2.4.4 21 2.4.5 Molybdenum 22 2.5 Discoveries from 1956 to 1978: The Era of Klaus Schwarz 22 2.5.1 Selenium 22 2.5.2 Chromium 24 2.5.3 Tin 24 2.5.4 Vanadium 25 2.5.5 Fluoride 25 2.5.6 Silicon 25 2.5.7 Nickel 26 2.5.8 Lead, Cadmium, and Arsenic 26 2.6 Current Trends and Problems 27 References 28

3. Iodine 33 Nicholas M. Alexander 3.1 Introduction 33 3.2 Chemistry of Iodine and Iodoamino Acids 34 3.2.1 Properties of Iodine 34 3.2.2 Iodine Isotopes 34 3.2.3 Important Chemical and Biochemical Reactions of Iodine 35 3.2.4 Iodotyrosines and Iodothyronines 37 3.3 Iodine Metabolism 39 3.3.1 Iodine Absorption, Evolution, and Thyroid Hormone Biosynthesis 39 3.3.2 Thyroid Hormones in Blood 42 3.3.3 Thyroid Hormones in Peripheral Tissues 43 3.3.4 Iodine Deficiency 44 3.3.5 Iodine Toxicity 45 3.4 Mechanism of Action of Thyroid Hormones 46 3.4.1 General and Cellular Effects 46 3.4.2 Structure-Activity Relationships 47 3.5 Summary 49 References 50 Contents xi

4. Fluorine 55 H. H. Messer 4.1 Introduction 55 4.2 Fluoride in Cells and Tissues 56 4.2.1 Mineralized Tissues 56 4.2.2 Cells and Soft Tissues 59 4.2.3 Extracellular Fluid 60 4.3 Fluoride Deficiency and Function 61 4.3.1 Deficiency 61 4.3.2 Functions of Fluoride 63 4.4 Metabolism and Toxicity of Fluoride 67 4.4.1 Metabolism 67 4.4.2 Toxicity 75 4.5 Summary 83 References 83

5. Manganese 89 Carl L. Keen, Bo Lonnerdal, and Lucille S. Hurley 5.1 Introduction 89 5.2 Manganese Concentration in Animal Tissues 89 5.3 Metabolism of Manganese 92 5.3.1 Absorption 92 5.3.2 Transport and Tissue Distribution 94 5.3.3 Excretion 96 5.4 Biochemistry of Manganese 97 5.4.1 Manganese Chemistry 97 5.4.2 Manganese as a Cofactor and in Metalloenzymes 98 5.4.3 Manganese and Carbohydrate Metabolism 104 5.4.4 Manganese and Lipid Metabolism 108 5.4.5 Manganese and Brain Function 110 5.5 Manganese Nutrition 112 5.5.1 Manganese Deficiency 112 5.5.2 Genetic Interactions and Manganese Metabolism 115 5.5.3 Human Requirements 117 5.5.4 Manganese Content of Foods 117 5.6 Manganese Toxicity 117 5.7 Manganese in Relation to Immunocompetence and Cancer 121 5.8 Summary 122 References 123 xii Contents

6. Cobalt 133 Roland S. Young 6.1 Introduction and History 133 6.2 Cobalt and Its Compounds in Cells and Tissues 134 6.2.1 Cobalt in Soils 135 6.2.2 Cobalt in Plants 135 6.2.3 Cobalt in Animals 137 6.3 Cobalt Deficiency and Function 138 6.3.1 Cobalt in Animal Nutrition 139 6.3.2 Cobalt in Human Nutrition 139 6.4 Metabolism and Toxicity of Cobalt 141 6.4.1 Effect of Cobalt on Plants 141 6.4.2 Effect of Cobalt on Animals 143 6.4.3 Effect of Cobalt on Microorganisms 143 6.4.4 Toxicity of Cobalt 144 6.5 Conclusion 146 References 146

7. Molybdenum 149 K. V. Rajagopalan 7.1 Introduction and History 149 7.2 Molybdenum and Its Compounds in Cells and Tissues 150 7.2.1 Molybdenum-Containing Enzymes 151 7.2.2 The Molybdenum Cofactor 162 7.2.3 General Aspects of Molybdenum Biochemistry 165 7.3 Nutritional Aspects of Molybdenum 167 7.3.1 Molybdenum in the Diet 167 7.3.2 Molybdenum Deficiency 168 7.3.3 Molybdenum Toxicity 169 7.4 Conclusion 170 7.5 Summary 170 References 171

8. Chromium 175 Janet S. Borel and Richard A. Anderson 8.1 Introduction 175 8.2 Chromium: Physical and Chemical Properties 175 Contents xiii

8.3 Biologically Active Chromium 176 8.4 Absorption and Transport of Chromium 177 8.5 Chromium Occurrence in Blood, Tissues, and Hair 178 8.5.1 Blood 179 8.5.2 Tissues 180 8.5.3 Hair 181 8.6 Chromium Excretion 182 8.7 Functions of Chromium and Signs of Chromium Deficiency 184 8.8 Factors Affecting Chromium Metabolism 187 8.9 Chromium and Stress 188 8.10 Dietary Requirements of Chromium 189 8.11 Effects of Chromium Supplementation 190 8.12 Toxicity of Chromium 193 8.13 Summary 194 References 195

9. Selenium 201 Raymond J. Shamberger 9.1 Introduction and History 201 9.2 Selenium and its Compounds in Cells and Tissues 204 9.2.1 Low Molecular Weight Compounds 204 9.2.2 Macromolecular Weight Compounds 207 9.3 Selenium Deficiency and Function 213 9.3.1 Dietary Liver Necrosis and Factor 3 213 9.3.2 Hepatosis Dietetica 216 9.3.3 Nutritional Muscular Dystrophy 216 9.3.4 Exudative Diathesis 217 9.3.5 Pancreatic Regeneration 218 9.3.6 Mulberry Heart Disease 218 9.3.7 Reproductive Problems 218 9.3.8 Myopathy of the Gizzard 220 9.3.9 Growth 220 9.3.10 Selenium-Responsive Unthriftiness of Sheep and Cattle 220 9.3.11 Periodontal Diseases of Ewes 221 9.3.12 Encephalomalacia 221 9.4 Metabolism and Toxicity of Selenium 222 9.4.1 Absorption 222 9.4.2 Excretion 224 9.4.3 Placental Transfer 225 9.4.4 Mechanism of the Antioxidant Action of Selenium 225 xiv Contents

9.4.5 Interactions of Selenium with Other Substances 228 9.4.6 Toxicity of Selenium 231 9.5 Summary 236 References 236

10. Vanadium 239 Barbara J. Stoecker and Leon L. Hopkins 10.1 Introduction and History 239 10.1.1 Discovery and History 239 10.1.2 Occurrence and Distribution 239 10.1.3 Nuclear and Chemical Characteristics 240 10.1.4 Essentiality 240 10.2 Vanadium in Tissues 240 10.2.1 Vanadium in Plants and Plant Products 240 10.2.2 Vanadium in Tunicates, Crustaceans, Shellfish, and Fish 241 10.2.3 Human Intakes of Vanadium 242 10.2.4 Vanadium Levels in Human Beings 242 10.3 Vanadium Deficiency and Function 243 10.3.1 Growth 243 10.3.2 Reproduction 243 10.3.3 Nutritional Edema 243 10.3.4 Manic-Depressive Illness 244 10.3.5 Dental Caries 244 10.3.6 Inotropic Effects of Vanadium 245 10.3.7 Vanadium and Renal Function 245 10.3.8 Vanadium and Glucose Metabolism 246 10.3.9 Vanadium and Lipid Metabolism 246 10.3.10 Vanadium and ATPases 247 10.3.11 Additional Effects of Vanadium 248 10.4 Vanadium Metabolism 248 10.4.1 Absorption of Vanadium 248 10.4.2 Tissue Distribution of Vanadium 249 10.4.3 Effects of Hormones on Vanadium Metabolism 249 10.4.4 Excretion of Vanadium 250 10.5 Vanadium Toxicity 250 10.5.1 Factors Affecting Toxicity of Vanadium 250 10.5.2 Toxicity in Chicks, Rats, and Sheep 250 10.5.3 Toxicity in Human Beings 251 10.6 Summary 252 References 252 Contents xv

11. Silicon 257 Edith Muriel Carlisle 11.1 Introduction 257 11.1.1 Discovery and History 257 11.1.2 Occurrence and Distribution 258 11.1.3 Chemistry 258 11.1.4 Essentiality 259 11.2 Silicon in Tissues 259 11.2.1 Primitive Organisms 259 11.2.2 Higher Plants 260 11.2.3 Animals and Man 262 11.3 Silicon Deficiency and Functions 264 11.3.1 Growth and Development 264 11.3.2 Calcification 265 11.3.3 Bone Formation 267 11.3.4 Cartilage and Connective Tissue Formation 269 11.3.5 Connective Tissue Matrix 270 11.3.6 Enzyme Activity 271 11.3.7 Connective Tissue Cellular Component 272 11.3.8 Structural Component 272 11.3.9 Aging 275 11.4 Metabolism 277 11.4.1 Absorption 277 11.4.2 Transport 278 11.4.3 Excretion 279 11.4.4 Interaction with Molybdenum 279 11.4.5 Enzyme Interaction 279 11.5 Toxicity 281 11.5.1 Pneumoconioses in Man 281 11.5.2 Silicosis 282 11.5.3 Asbestosis 283 11.5.4 Renal Toxicity 284 11.6 Summary 287 References 288

12. Nickel 293 Forrest H. Nielsen 12.1 Introduction and History 293 12.2 Nickel and Its Compounds in Cells and Tissues 293 12.3 Nickel Deficiency 296 xvi Contents

12.4 Nickel Function 300 12.5 Biological Interactions between Nickel and Other Trace Elements 301 12.6 Nickel Metabolism and Toxicity 304 12.7 Summary 306 References 307

13. Tin 309 David B. Milne 13.1 Introduction 309 13.2 Tin in Cells and Tissues 309 13.2.1 Chemical Properties 309 13.2.2 Distribution in Mammalian Tissues 311 13.3 Deficiency and Function 311 13.4 Metabolism and Toxicity 312 13.4.1 Inorganic Tin 312 13.4.2 Organotin Compounds 315 13.5 Summary 316 References 316

14. Arsenic 319 Forrest H. Nielsen and Eric O. Uthus 14.1 Introduction and History 319 14.2 Arsenic and Its Compounds in Cells and Tissues 320 14.3 Arsenic Deficiency and Interaction with Other Nutrients 323 14.4 Arsenic Function 327 14.5 Arsenic Metabolism 328 14.6 Arsenic Toxicity 334 14.7 Summary 335 References 336

15. Cadmium 341 Harry A. Smith 15.1 Introduction 341 15.1.1 Historical Perspectives and Properties of Cadmium 341 15.1.2 Metallothionein and Its Interactions with Cadmium 342 15.2 Chemistry of Cadmium: Biological Perspectives 345 15.2.1 General Chemical Properties of Cadmium 345 15.2.2 Biological Implications 345 Contents xvii

IS.3 Evidence for the Possible Essentiality of Cadmium 346 IS.4 Metabolism of Cadmium 348 IS.4.1 Absorption of Cadmium 348 IS.4.2 Transport of Cadmium in Blood 3S0 IS.4.3 Organ, Tissue, and Subcellular Distribution of Cadmium 3S1 IS.4.4 Cadmium Excretion 3S2 IS.S Biochemical Effects of Cadmium 3S4 IS.S.1 Nucleic Acid and Protein Synthesis 3S4 IS.S.2 Induction of Thionein by Cadmium 3S7 IS.S.3 Other Biochemical Effects of Cadmium 360 IS.6 Summary 362 References 363

16. Lead 367 A. M. Reichlmayr-Lais and M. Kirchgessner 16.1 Introduction and History 367 16.2 Metabolism of Lead 368 16.2.1 Occurrence and Intake 368 16.2.2 Absorption of Lead 369 16.2.3 Excretion of Lead 370 16.2.4 Transport and Distribution 370 16.2.S Interactions 373 16.3 Lead Deficiency 37S 16.4 Toxicity of Lead 376 16.4.1 Hematologic Effects of Toxic Lead Doses 377 16.4.2 Neurotoxic Effects of Lead 379 16.4.3 Renal Effects of Toxic Lead 381 16.4.4 Intranuclear Inclusion Body 382 16.4.S Mutagenic, Mitogenic, and Teratogenic Effects of Lead 382 16.S Conclusions 383 References 384

17. Boron 389 Carol J. Lovatt and W. M. Dugger 17.1 Boron in Biology 389 17.1.1 Introduction 389 17.1.2 Criteria for Essentiality 389 l7.1.3 Effect of Boron on the Growth of Organisms 390 l7.1.4 Plant Evolution and an Essential Role for Boron 392 xviii Contents

17.1.5 Boron Toxicity 393 17.1.6 Problems Associated with Studies of Boron Metabolism 394 17.1.7 lOB (n, ex) 7Li Nuclear Reaction 394 17.1.8 Therapeutic Uses for Boron and Organoborates in Medicine 395 17.2 Carbohydrate Metabolism 396 17.2.1 Boron Complexes 397 17.2.2 Sugar Translocation 398 17.2.3 Photosynthesis 398 17.2.4 Respiration 399 17.2.5 Starch 399 17.2.6 Cellulose and Cell Wall Glucans 400 17.2.7 Phenols 401 17.2.8 Lignin 402 17.2.9 Boron in Enzymic Reactions 402 17.2.10 Pollen Germination 404 17.2.11 Conclusions 405 17.3 Hormone Action 405 17.4 Membrane Structure and Function 409 17.5 Nucleic Acid Biosynthesis 410 17.6 Summary 414 References 415

Index 423