Clinical Biochemistry of Domestic Animals (Sixth Edition) - UMK ...

Chapter 9
Iron Metabolism and Its Disorders
John W. Harvey
Department of Physiological Sciences
College of Veterinary Medicine
University of Florida
Gainesville, Florida
I. INTRODUCTION
II. IRON DISTRIBUTION
A. Hemoglobin
B. Storage Iron
C. Myoglobin
D. Tissue Iron
E. Plasma Iron
III. IRON ABSORPTION
IV. PLASMA IRON TRANSPORT
V. REGULATION OF IRON METABOLISM
A. Intracellular Regulation of Iron Metabolism
B. Systematic Regulation of Iron Metabolism
VI. IRON METABOLISM IN CELLS
A. Iron Metabolism in Erythroid Cells
B. Iron Metabolism in Macrophages
C. Iron Metabolism in Hepatocytes
VII. TESTS FOR EVALUATING IRON METABOLISM
A. Hematology
B. Serum Iron
C. Serum Total Iron-Binding Capacity
D. Serum Ferritin
E. Bone Marrow Iron
F. Erythrocyte Zinc Protoporphyrin
G. Tissue Nonheme Iron
H. Ferrokinetics
VIII. DISORDERS OF IRON METABOLISM
A. Iron Deficiency
B. Anemia of Inflammatory Disease
C. Portosystemic Shunts
D. Copper Deficiency
E. Iron Overload
F. Siderotic Inclusions in Erythroid Cells
REFERENCES
I. INTRODUCTION
Iron is an essential nutrient required in a wide variety of
metabolic processes. In solution, iron exists in two oxidation
states, ferrous (Fe 2 ) and ferric (Fe 3 ), which can donate
or accept electrons, respectively. Iron is typically in the
Fe 2 state for transport across membranes and in the Fe 3
state when bound to transport and storage proteins. Iron
may be in either oxidation state when present in heme and
iron-sulfur (Fe-S) cluster-containing proteins. The ability
of iron to vary in oxidation state and redox potential,
depending on the ligands it forms, enables iron to serve
multiple functions. Iron-containing proteins are critical for
oxygen transport and storage, respiration, DNA synthesis,
citric acid cycle function, and various enzymatic reactions.
Unfortunately, the same physical characteristics that allow
iron to function as a cofactor in controlled redox biochemistry
also makes iron potentially toxic to cells, because
of its ability to catalyze the formation of reactive oxygen
species. The binding of iron to coordinating ligands, such
as O, N, and S, in proteins and the tight regulation of iron
uptake, transport, and storage tends to shield iron from
reactions with molecular oxygen that generate free radicals
and injure tissues ( Ryan and Aust, 1992 ).
Iron is absorbed from the diet in the small intestine and
transferred to plasma, where it is bound to transferrin for
transport to cells within the body. Once inside the body,
iron cycles in a nearly closed system ( Fig. 9-1 ) because
little iron is lost in domestic animals unless hemorrhage
occurs ( Finch et al ., 1978 ). About 75% of the iron present
in plasma will be transported to the bone marrow for incorporation
into hemoglobin in developing erythroid cells
( Smith, 1997 ). The remaining plasma iron is taken up by
nonerythroid tissues, primarily the liver ( Koury and Ponka,
2004 ). Erythrocytes containing hemoglobin normally circulate
for several months before being phagocytized by macrophages
when senescent. After phagocytosis, erythrocytes
are lysed, hemoglobin is degraded, and iron is released.
Most iron from degraded hemoglobin is quickly released
back into plasma, but a small amount may be stored as ferritin
or hemosiderin within macrophages, which is released
more slowly into plasma. The vast majority of iron entering
plasma each day comes from macrophage release.
Clinical Biochemistry of Domestic Animals, 6th Edition 259
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