Hemoglobin synthesis

A system of internal iron exchange exists which is dominated by the iron required for hemoglobin synthesis. For formation of red blood cells, iron stores can furnish 10—40 mg/d of iron, as compared to 1—3 mg from dietary sources (74). Only ca 10 wt % of ingested iron actually is absorbed. 

Iron is another vital nutrient in the development of functioning erythrocytes it is essential for the formation of hemoglobin. Lack of iron leads to a decrease in hemoglobin synthesis and ultimately red blood cells. Normal homeostasis of iron transport and metabolism is depicted in Fig. 63-2.7 Approximately 1 to 2 mg of iron is absorbed through the duodenum each day, and the same amount is lost via blood loss, desquamation of mucosal cells, or menstruation. 

Iron appeared to reduce the effects of orally or subcutaneously administered lead on blood enzyme and liver catalase activity (Bota et al. 1982). Treatment of pregnant hamsters with iron- or calcium-deficient diets in conjunction with orally administered lead resulted in embryonic or fetal mortality and abnormalities (ranting, edema) in the litters, while treatment with complete diets and lead did not (Carpenter 1982). Inadequate levels of iron in association with increased body burdens of lead enhanced biochemical changes associated with lead intoxication (Waxman and Rabinowitz 1966). Ferrous iron was reported to protect against the inhibition of hemoglobin synthesis and cell metabolism by lead it has been speculated that iron competes with lead uptake by the cell (Waxman and Rabinowitz 1966). In... 

Waxman HS, Rabinowitz M. 1966. Control of reticulocyte polyribosome content and hemoglobin synthesis by heme. Biochim Biophys Acta 129 369-379. 

The Nobel Prize chemist Linus Pauling related the mechanism of sickle cell anemia to a genetic defect in hemoglobin synthesis and thus defined the first molecular disease. Pauling s groundbreaking paper in 1949 was boldly titled Sickle Cell Anemia A Molecular Disease. Many claim that this discovery laid the foundation for molecular biology. What is the chemistry that is at the heart of this pioneering work ... 

Disorders of hemoglobin synthesis Inadequate production of mature RBCs Deficiency of nutrients (B]2, folic acid, iron, protein)... 

Cell multiplication is inhibited because DNA synthesis is insufficient. This occurs in deficiencies of vitamin Bu or folic acid (macrocytic hyperchromic anemia). 2. Hemoglobin synthesis is impaired. This situation arises in iron deficiency, since Fe + is a constituent of hemoglobin (microcytic hypochromic anemia). 

Iron deficiency is usually due to blood loss, or more rarely to inadequate iron uptake. During pregnancy, increased demand can also cause iron deficiency states. In severe cases, reduced hemoglobin synthesis can lead to anemia ( iron-deficiency anemia ). In these patients, the erythrocytes are smaller and have less hemoglobin. As their membrane is also altered, they are prematurely eliminated in the spleen. 

Lead exposure can produce a number of other effects. One of the most common effects is on the red blood cells, which results in anemia. The red blood cells become fragile and hemoglobin synthesis is impaired. Changes in the red blood cells and some enzymatic changes were used as a marker for lead exposure. Similar to other metals, lead adversely affects kidney function, but this is now rare with reductions in occupational exposure. Several studies have demonstrated that elevated lead exposure is related to elevated blood pressure levels, particularly in men. There appears to be a weak association between lead exposure and increased incidence of lung and brain cancer. Lead exposure is a reproductive hazard for both males and females. In males, lead affects sperm count and sperm motility, resulting in decreased offspring. 

Manganese is a cofactor of enzymes involved in energy metabolism and is required for hemoglobin synthesis, thiamin utilization and tendon and bone formation. Unlike nutrients that fulfil unique func-... 

Haemosiderin An iron-protein molecule inter alia, a source of the iron required for hemoglobin synthesis. 

T8. Relationship between Folic Acid Deficiency and Anemia Folic acid deficiency, believed to be the most common vitamin deficiency, causes a type of anemia in which hemoglobin synthesis is impaired and erythrocytes do not mature properly. What is the metabolic relationship between hemoglobin synthesis and folic acid deficiency ... 

Very toxic to most plants cumulative poison in mammals. Inhibits 6-aimnolevulinate dehydra se and thus hemoglobin synthesis in mammals (see Al). One of the symptoms of lead poisoning is anemia. Toxic to central nervous system. 

Copper was recognized as nutritionally essential by 1924 and has since been found to function in many cellular proteins.470-474 Copper is so broadly distributed in foods that a deficiency has only rarely been observed in humans.4743 However, animals may sometimes receive inadequate amounts because absorption of Cu2+ is antagonized by Zn2+ and because copper may be tied up by molybdate as an inert complex. There are copper-deficient desert areas of Australia where neither plants nor animals survive. Copper-deficient animals have bone defects, hair color is lacking, and hemoglobin synthesis is impaired. Cytochrome oxidase activity is low. The protein elastin of arterial walls is poorly crosslinked and the arteries are weak. Genetic defects in copper metabolism can have similar effects. 

In plasma, ca 90 vvl or copper is in the ineialloprotein ceruloplasmin. also known as ay-globulin, mol wi 151.000. which contains 8 atoms of copper per molecule. Ceruloplasmin has been identified as a ferroxi dasctll which catalyses Ihc oxidation of aromatic amines and of Pc to Fe . The ferric ion is then incorporated inlo iranslcrrin which is necessary lor the transport ol iron to tissues involved in Ihe synthesis or iron-containing compounds, e.g.. hemoglobin. Lowered levels of ceruloplasmin interfere with hemoglobin synthesis. 

The regulation of translation through the phosphorylation of eIF-2 is best understood as it operates in the rabbit reticulocyte. Two protein kinases specific for the a subunit of eIF-2 have been purified from reticulocytes. One of these kinases, termed the heme-regulated inhibitor repressor (HRI), serves to coordinate the rate of hemoglobin synthesis (more than 90% of the total protein synthesized in the reticulocyte is hemoglobin) with the availability of hemin (the... 

The use of chelating or complexing agents to treat metabolic dysfunction. The classical example is the use of D-penicillamine to treat Wilson s disease, which is caused by an inability of the body to metabolize copper in the normal way. Another example is the use of desferrioxamine for iron overload in Cooley s anemia, which is caused by a fault in hemoglobin synthesis. 

Anemia may result from other complications even when iron supply is sufficient. A decrease in hemoglobin synthesis, a fault in transport mechanisms or destruction of erythrocytes have all been noted. Sideroblastic or iron-loading anemias are characterized by a fault in iron metabolism (see Section 62.2.3.2). There are also several other syndromes of iron deficiency known clinically, including pica and Goodpasture s syndrome (an immune-related lung and kidney disease). The different categories of anemia have been discussed in detail by Prasad.48... 

Lin J-L, Kou —T, Leu M-L. 1996. Effect of long-term low-dose aluminum-containing agents on hemoglobin synthesis in patients with chronic renal insufficiency. Nephron 74 33-38. 

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