Joseph E. Smith

Iron Metabolism and Its Disorders

Publisher Summary Iron is the second most abundant metal and the fourth most common element. Unfortunately, it is chemically unstable and is easily oxidized to an insoluble ferric form, which is the form found in rocks and soils. Ferric iron is unavailable for most biological systems. All living organisms, except possibly Lactobacillus, require iron. It is important for biological processes because it can exist in two oxidation states: Fe 2+ and Fe 3+, which can be easily interconverted. Iron is so inaccessible that organisms use a variety of mechanisms to get iron from their environments. Because free iron can catalyze free radicals from molecular oxygen and hydrogen ions, it can have disastrous consequences for biological materials. So, intracellular iron is bound to or incorporated into various proteins or other chelates to reduce its toxicity. Those proteins or chelates are responsible for the absorption, storage, and biological activity of iron. Study of iron metabolism involves a study of the physiological compounds associated with it.

Serum Ferritin and Total Iron-Binding Capacity to Estimate Iron Storage in Pigs

The inability to accurately determine storage iron in baby pigs limits the development of new treatment programs. In pigs treated neonatally with iron dextran, serum ferritin had increased dramatically at ten days of age and then returned to near preinjection levels by 50 days of age. In contrast, serum ferritin in untreated pigs declined until they were offered creep feed at 21 days of age. When serum ferritin, serum iron, serum total iron-binding capacity, erythrocyte number, packed cell volume, and blood hemoglobin were measured in three-week-old pigs, serum ferritin combined with serum total iron-binding capacity correlated significantly with the total nonheme iron in the liver and spleen. The nonheme iron (in mg) could be predicted (r2 = 0.71) by the following expression: 8.7 + 0.6 (ferritin in ng/ml).

Enzyme-linked immunosorbent assay to measure serum ferritin and the relationship between serum ferritin and nonheme iron stores in cats

Serum ferritin concentration correlates with tissue iron stores in humans, horses, calves, dogs, and pigs but not in rats. Because serum iron and total iron-binding capacity can be affected by disorders unrelated to iron adequacy (such as hypoproteinemia, chronic infection, hemolytic anemia, hypothyroidism, and renal disease), serum ferritin is probably the most reliable indicator of total body iron stores in larger species. To test the hypothesis that serum ferritin might be correlated with tissue iron levels in cats, we developed a quantitative enzyme-linked immunosorbent assay that uses two monoclonal antibodies in a sandwich arrangement to measure feline serum ferritin. The recovery of purified ferritin added to feline sera ranged from 94% to 104%; the within-assay coefficient of variability was 8.4%, and the assay-to-assay variability was 13.2%. Mean serum ferritin from 40 apparently healthy cats was 76 ng ml (SD = 24 ng/ml). Serum ferritin concentration was significantly correlated (P < 0.001, n = 101, r = 0.365) with the nonheme iron in the liver and spleen (expressed as milligrams of iron per kilogram of body weight), as determined by Pearson product-moment correlation analysis. Because serum iron can decrease in diseases other than iron deficiency, the combination of serum iron and serum ferritin should provide sufficient evidence to differentiate anemia of chronic inflammation from anemia of iron deficiency in the cat.

Reactivity of lectins with feline erythrocytes

Blood groups A, B and AB of cats (not related to human blood groups) are defined serologically with feline antisera. Five cats were blood typed and used in this study. Three cats were type B; two were type A. Two per cent suspensions of red blood cells (RBCs) from each cat were prepared and used in agglutination tests with 11 commercial lectins. Lectins are carbohydrate-binding proteins of non-immune origin. Most of these lectins agglutinated either all or none of the five samples of RBCs. However, wheat germ lectin (WGL) strongly agglutinated feline type B RBCs, but did not agglutinate type A RBCs. Thus WGL may be useful in feline blood typing, especially because the naturally occurring anti-B isoagglutinin is of low incidence and low titre.

Influence of erythrocyte age on enzyme activity in the bovine.

Abstract 1. 1. Several enzymatic activities—involving nine in the glycolytic pathway, two in the hexose monophosphate pathway and two in other pathways—were measured in bovine erythrocytes using techniques designed to detect erythrocyte aging. 2. 2. Although the activity of most enzymes was increased in the lighter, younger erythrocytes, only glutathione reductase was significantly elevated. 3. 3. In the more osmotically resistant erythrocytes, 6-phosphogluconate dehydrogenase was significantly increased and glyceraldehyde-3-phosphate dehydrogenase significantly decreased. 4. 4. Hexokinase, glucose phosphate isomerase, pyruvate kinase, glucose-6-phosphate dehydrogenase, 6-phosphogluconate dehydrogenase, glutathione reductase and glutamate-oxalacetate transaminase were significantly elevated during erythropoietic response. 5. 5. All enzymes measured, except aldolase, were significantly elevated in the more osmotically resistant erythrocytes produced during erythropoietic response.

Glucose-6-phosphate dehydrogenase deficiency in a dog.

After screening 3,300 dogs, one animal with a mild deficiency of erythrocyte G6PD was detected. Although it had several clinical problems for 2 months, no abnormality could be directly attributable to the reduced enzymatic activity. Biochemically the mutant was electrophoretically slower but within the normal range for Km-G6P, Km-NADP, use of 2-dG6P and deamino NADP, pH optimum, and heat stability.

Species differences in erythrocyte glutathione reduction rates after oxidation with t-butyl hydroperoxide☆

1. 1. Erythrocyte glutathione reduction rates were determined in several animal species and man using t-butyl hydroperoxide as the oxidant. 2. 2. The relative rates for the different species were similar to those reported previously, but the absolute values were considerably higher. 3. 3. This difference was attributed to the specificity of t-butyl hydroperoxide for GSH.

Effect of Copper on Red Cell Glutathione and Enzyme Levels in High and Low Glutathione Sheep

Summary Effects of copper on red cell glutathione and enzyme levels were investigated in sheep of high- and low-glutathione types. No significant differences were observed in copper induced inhibition of glutathione regeneration or erythrocyte enzyme activities in the two groups of sheep. These results, together with those showing the effect of copper on GSH oxidation suggest that low-glutathione sheep should not be more sensitive to small doses of copper, commonly encountered in chronic copper poisoning in sheep than are high-glutathione sheep.

Congenital Anemia, Dyskeratosis, and Progressive Alopecia in Polled Hereford Calves:

A new syndrome of anemia, alopecia, and dyskeratosis was identified in Polled Hereford calves in this study. Cutaneous changes included hyperkeratosis and hair loss around the muzzle and ear margins, which progressed to a generalized alopecia and hyperkeratotic dermatitis. Histologically, orthokeratotic hyperkeratosis with dyskeratosis of epidermal and follicular keratinocytes was present. Alopecia was correlated with dyskeratosis of Huxleys layer and an increasing proportion of follicles in the telogen phase of the hair cycle. Dermatitis was characterized by a mild dermal mononuclear cell infiltrate and mild lymphocytic perivascular dermatitis. The anemia present at birth was nonprogressive and was classified as normochromic and normocytic to macrocytic. Reticulocytosis was absent, but bone marrow was markedly hyperplastic. Nuclear cytoplasmic asynchrony of the rubricyte and metarubricyte stages occurred in the bone marrow. Abnormal rubricyte nuclei and maturation arrest at the late rubricyte stage were common. Cytologic features of the erythroid series are similar to those of type I congenital dyserythropoietic anemia of human beings. Genealogic features suggest that this is a primary hereditary defect. The mode of inheritance, however, remains to be determined.

Elevation rate of glycosylated hemoglobins in dogs after induction of experimental diabetes mellitus

The glycosylated hemoglobin, hemoglobin A1c, (HbA1c), which reflects average plasma glucose of the previous few weeks, has recently been used to monitor humans with diabetes mellitus. Further understanding of the HbA1c elevation rate would improve interpretation of HbA1c. We determined glycosylated hemoglobin elevation rates in 5 dogs with induced diabetes. Hemoglobin A1C was determined by an established column chromatographic technique; plasma glucose by glucose oxidase. Values were determined on 13 normal dogs and compared with values obtained weekly from surgically or chemically induced diabetic dogs. Hemoglobin A1c increased in a fashion that could be predicted by modelling. The model predicts that large changes in Hb A1c will occur within the first few weeks of a sudden change in glucose and that a new plateau will be reached at a time equal to the erythrocyte life span. In the present experiment abnormally elevated HbA1c occurred after 2 wk of hyperglycemia. The results should approximate the elevation rate after acute onset and sustained severe hyperglycemia in humans, because humans and canine are hematologically similar and thus extend previously reported studies on human out-patient diabetics.