Iron Metabolism

398 Pages·1983·8.895 MB·English

by  Iván Bernát M.D., D.Sc. (auth.)

IRON METABOLISM
IRON METABOLISM
IV AN BERNAT, M.D., D.Se.
PROFESSOR OF HEMATOLOGY
PLENUM PRESS, NEW YORK
TRANSLATED BY
EVA GOSZTONYI
PUBLISHED IN THE U.S.A. BY
PLENUM PRESS
A DIVISION OF
PLENUM PUBLISHING CORPORATION
233 SPRING STREET, NEW YORK, N.Y. 10013
ISBN-13: 978-1-4615-7310-4 e-ISBN-13: 978-1-4615-7308-1
DOl: 10.1007/978-1-4615-7308-1
JOINT EDITION PUBLISHED WITH
AKADEMIAI KIADO, BUDAPEST, HUNGARY
© AKADEMIAI KIADO, BUDAPEST 1983
Softcover reprint of the hardcover 1st edition 1983
CONTENTS
Chapter 1. The Distribution of Iron in Nature 9
The basic physical, chemical, and biochemical properties
of iron 9
Bibliography 12
Chapter 2. Biochemical Evolution of the Heme-Type Enzymes 15
Bibliography 17
Chapter 3. The Biological Significance of Iron-Containing Compounds 19
Bibliography 22
Chapter 4. Distribution and Function of the Iron-Containing Complexes
of the Human Organism 23
Heme iron compounds 23
Storage iron 24
Transport iron 24
Other non-heme iron compounds 24
Bibliography 26
Chapter 5. Dietary Iron 27
Iron intake 27
Bibliography 34
Chapter 6. Iron Absorption 37
Factors influencing iron absorption 38
The control of iron absorption 47
Measurement of iron absorption 60
Bibliography 64
Chapter 7. Iron Transport 71
Plasma iron 71
Transferrin 78
Bibliography 85
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Chapter 8. Storage Iron 91
Ferritin and hemosiderin 91
Deposition and mobilization of iron 95
Quantitative aspects of iron stores 97
Clinical methods used for the estimation of available iron
stores 103
Bibliography 108
Chapter 9. Iron Loss and Iron Requirement 113
Iron loss in women 119
Iron requirements for newborns, infants, and children 124
Bibliography 134
Chapter 10. Erythropoiesis 141
Bibliography 145
Chapter 11. Hemoglobin Synthesis 147
Biosynthesis of heme 149
Biosynthesis of globin 155
Bibliography 155
Chapter 12. Red Cell Destruction 159
Bibliography 160
Chapter 13. Hemoglobin Catabolism 161
Bibliography 164
Chapter 14. Ferrokinetics 167
Survey 167
Plasma iron clearance and plasma iron transport rate 170
Incorporation of radioiron into the erythroblasts and
reticulocytes. Iron utilization in the course of red cell
production. Effective erythropoiesis 173
Distribution of iron among the bone marrow, liver, and
spleen 176
Bibliography 179
Chapter 15. Erythrokinetics 183
Red cell production 184
Red cell destruction 185
Bibliography 197
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Chapter 16. Cytochemical Stains and Microscopy 201
Siderocytes 201
Sideroblasts 202
Sideromacrophages 203
Bibliography 203
Chapter 17. Electron Microscopic Investigations 205
Ferritin 205
Hemosiderin 205
Erythrophagocytosis 206
Iron transport 207
Rhopheocytosis 209
Sideroblasts and siderocytes 211
Bibliography 213
Chapter 18. Iron Deficiency 215
Incidence 215
The clinical picture of iron deficiency 218
Laboratory findings 233
Ferrokinetics 238
The diagnosis of iron deficiency 239
Differential diagnosis of iron deficiency 242
Etiology and pathogenesis of iron deficiency 242
Therapy of iron deficiency 245
Acute iron intoxication 257
Bibliography 258
Chapter 19. Anemia of Infection 275
Differential diagnosis 279
Treatment 280
Bibliography 280
Chapter 20. Anemia of Thermal Injury 285
Development, type, and course of the anemia of thermal
injury 285
Therapy 295
Bibliography 295
Chapter 21. Protein~Deficiency Anemia 299
Vitamin E deficiency 300
Bibliography 300
Chapter 22. Pernicious Anemia 301
Bibliography 303
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Chapter 23. Hemolytic Anemias 305
Bibliography 306
Chapter 24. Refractory Hypochromic Anemias 309
The sideroblastic anemias 309
Pyridoxine-responsive anemias 313
The disturbance of heme synthesis in thalassemia 315
Pathological heme synthesis associated with lead and
other toxic substances 317
Sideroblastic anemias arising in connection with anti-
tuberculous drugs 319
Shahidi-Nathan-Diamond anemia 319
Fanconi's anemia 320
Genetically determined microcytic hypochromic anemias 320
Bibliography 321
Chapter 25. Disturbed Iron Metabolism in Acute Radiation Injury 327
Bibliography 333
Chapter 26. Iron Metabolism in Polycythemia Vera and Secondary
Polycythemias 335
Bibliography 337
Chapter 27. Iron Overload .339
Idiopathic hemochromatosis (Iron storage disease) 340
Secondary hemochromatosis associated with cirrhosis of
the liver 356
Congenital atransferrinemia 358
Congenital (familial) hypersiderosis 360
Nutritional siderosis - Bantu siderosis 360
Siderosis developing in refractory anemias associated
with ineffective erythropoiesis 364
Transfusional siderosis 364
Renal hemosiderosis 367
Idiopathic pulmonary hemosiderosis 368
Goodpasture syndrome 370
Bibliography 371
Author Index 383
Subject Index 399
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CHAPTER I
THE DISTRIBUTION OF IRON IN NATURE
THE BASIC PHYSICAL, CHEMICAL, AND BIOCHEMICAL
PROPERTIES OF IRON
Iron, in the form of various combined ores, is one of the most common elements,
constituting about 5% of the earth's crust. The most important iron-containing
minerals are the oxides and sulfides. Hematite (red iron ore, Fe20 3), magnetite
(loadstone, Fe30 4), and goethite (hydrous iron oxide, Fe02H) belong to the former
group, whereas pyrite (FeS2) and marcasite (formerly crystallized iron pyrite, FeS2)
belong to the latter. Iron is also present in meteorites, in other planets, and in the
sun. Iron is found in both sea and fresh water but only those springs whose water
contains at least 10 mg/kg of iron are regarded as medicinal iron springs. Euthermic
or hyperthermic springs of high iron content in which blue algae and iron bacteria
are present are classified as iron thermae (siderophytathermae or F-thermae), e.g.,
Yamagataken, Yiraka, Yamazaki in Japan.
Pure metallic iron is rare in nature; it is bluish white and strongly magnetic. It is
unstable, being di-, tri-, or occasionally sexvalent. Its atomic number is 26, its atomic
weight 52-61. Thus its nucleus contains 26 protons and 26-35 neutrons. The four
stable iron isotopes have an atomic weight of 54, 56, 57, and 58, giving an atomic
weight of the naturally occurring iron of 55.847. Around the atomic nucleus of the
iron 2 + 8 + 14 + 2 = 26 electrons circulate in four "shells."
Six of the ten isotopes of iron are radioactive; 52Fe has a half-life of 8.4 hours,
53Fe - 9 minutes, 55Fe - 2.6 years, 59Fe - 45.1 days, 60Fe - 3.105 years, 61Fe_
6.1 minutes. 59Fe, 55Fe and 52Fe are all useful in medical and biological studies,
the first two being the most widely used.
Iron derivatives may be divalent ferrous compounds, e.g., FeS04, trivalent ferric
compounds, e.g., FeZ(S04h, or complex iron compounds, e.g., K4[Fe(CN6)], in
which the iron is a part of a complex anion. The ferrous salts are white in the
dehydrated form while their hydrates and solutions are light green. The ferric salts in
the dehydrated form are white or light violet, their hydrates and solutions being
yellow or brown.
Iron, owing to its oxidoreduction and to its complex forming properties, is a
central constituent of the enzymes that regulate the oxidoreduction processes of
tissues (iron porphyrin proteids, "tissue hemins"). These enzymes were probably
among the first intracellular compounds developed in primitive organisms, and
9
hence they have a general biological significance. The iron porphyrin proteids of
hemoglobin and myoglobin were developed only at a later stage of evolution.
In addition to its role in tissue respiration, iron is also involved in oxidative
phosphorylation, porphyrin metabolism, collagen synthesis, lymphocyte and
granulocyte function, tissue growth, and neurotransmitter synthesis and catabolism
(Pollitt and Leibel, 1976; Leibel et aI., 1978).
Iron may also be involved in the nonspecific defense reactions of the organism.
In the past three decades several iron-containing metabolites (siderochromes) have
been isolated from cultures of microorganisms (Bickel et aI., 1960; Prelog, 1964).
Most of these, even in high dilution, possess considerable biological activity; some
promote growth of bacteria (sideramines), others have an antibiotic effect
(sideromycins).
The first sideromycin (Grisein) was discovered by Reynolds, Schatz, and
Waksman in 1947, and albomycin was isolated by Gause and Brazhnikova in 1951.
In 1952 the isolation of several sideramines was reported. Neilands (1952)
described ferrichrome, Hesseltine et aI. (1952) coprogen, Lochhead and his team
(1952) the terregens factor. The isolation of the ferrioxamines from Actinomyces
cultures was achieved by Bickel and his collaborators (1960a, b, c, d). Zahner et aI.
(1960) recognized the antagonism between the sideramines and sideromycins. This
recognition had a significant influence on the further investigation of these
compounds. Between 1961 and 1963 the structure of the ferrioxamines was
successfully established, and this enabled the complete or partial synthesis of these
compounds (Bickel et aI., 1960; Keller-Schierlein and Prelog, 1962; Prelog and
Walser, 1962). They proved to be ferric complexes with three hydroxamic acid
[CO-N(OH)] groups (Fig. 1/1 and Table 1/1).
Table 1/1
Siderochromes
Sideramines Sideromycins
Ferrichrome Ferrioxamine A Grisein
Coprogen Ferrioxamine B Albomycin
Terregens factor Ferrioxamine C
Ferrioxamine D) Ferrimycin A)
Ferrioxamine D2 Ferrimycin A2
Ferrioxamine E Ferrimycin B
Ferrioxamine F ETH 22765
Ferrioxamine G
F errichrysin LA 5352
F erricrocin LA 5937
Ferrirhodin
Ferrirubine
10
Fig. 1/1. Structural formula of ferrioxamine-B (after Prelog, Y., in: Gross, F.: Iron Metabolism.
Springer, Berlin-Giittingen-Heidelberg 1964)
Fig. 1/2. Effect of different concentrations of ferrioxamine-B upon the growth of Microbacterium
lacticum ATCC 8181 (after Prelog, Y., in: Gross, F.: Iron Metabolism. Springer,
Berlin-Giittingen-Heidelberg 1964)
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