Hemoglobin, biosynthesis

Like folate and vitamin C, vitamin B6 (pyroxidine) is water soluble and like folate has several vitamers. Vitamin B6 may be involved in more bodily functions than any other nutrient (Tambasco-Studart et al., 2005), is a cofactor for many enzymes, especially those involved in protein metabolism, and is also a cofactor for folate metabolism. Vitamin B6 has anticancer activity (Theodoratou et al., 2008), is a strong antioxidant (Denslow et al., 2005), is involved in hemoglobin biosynthesis, lipid and glucose metabolism and immune and nervous system function. Possible consequences of deficiency include anemia, impaired immune function, depression, confusion, and dermatitis (Spinneker et al., 2007). Vitamin B6 deficiency is generally not a problem in the developed world, but there could be as yet poorly defined consequences of suboptimal intake particularly for the elderly. 

Hemoglobin H and Hb Barts are usually found in pathologic conditions, where normal hemoglobin biosynthesis is diminished. This occurs, for instance, in certain types of thalassemias (see Chapter 14). 

In conclusion, we befieve there is now ample evidence that the copper protein of serum, ceruloplasmin, is a molecular link between copper and iron metabohsm. It has been shown both in vitro and in vivo to be directly involved in iron mobilization, the rate of formation of Fe(III) transferrin, and perhaps ultimately of hemoglobin biosynthesis. While the precise mechanism of this effect is still under investigation, we believe that it is directly related to the ferroxidase activity of this serum enzyme. 

Blood lead levels are the primary criteria by which health professionals determine whether a child is currently suffering from lead poisoning (10). However, it is important to note that BLLs only provide a marker of very recent exposure, because the half-life for lead in blood is 2-3 weeks (5). To determine long-term exposure to lead, effects on hemoglobin biosynthesis (see below) or total bone lead must be used (10). The Centers for Disease Control recommend that all children should have their BLL screened at ages 1 and 2 if they meet one or more of the following criteria (17) ... 

From blood, iron is transferred to tissue, where it may be (1) used for hemoglobin biosynthesis (hematopoietic tissue) (2) stored in a variety of tissues (about 100-300 mg of the iron) or (3) used for the biosynthesis of such enzymes as cytochromes, peroxidases, and catalases. 

In iron deficiency anemia, Zn2+ may be used instead of iron by ferro-chelatase in the biosynthesis of heme. Red blood cell lysates in such instances contain increased quantities of Zn-hemoglobin. In addition, red cells from iron-deficient patients also contain increased amounts of protoporphyrin IX. Zinc-hemoglobin and protoporphyrin IX determinations are thus used in the diagnosis of iron deficiency anemia. 

Transferrin is a single-chain glycoprotein that binds 2 g-atoms of ferric iron per mole of protein. The iron is chelated via tyrosyl and histidyl residues, and the complex is extremely stable at physiologic pH. The function of transferrin is to transport iron throughout the human organism, especially to the immature red cells, which cannot effectively acquire iron for the biosynthesis of hemoglobin unless it is presented to them in combination with transferrin. Specific transferrin receptors are present on the surface of such immature red cells as well as in all other tissues. Receptor-mediated endocytosis (see Chapter 9) is believed to be the main means of transferrin-bound iron entry into cells. Transferrin is also believed to be antimicrobial because it withholds iron from microorganisms. 

Probably the most intriguing and important properties of transferrin are those involved in its physiological role as the source of iron for the biosynthesis of hemoglobin by the immature red blood cell. About 30 mg of iron are incorporated into hemoglobin synthesized by the normal adult bone marrow each day, or about 10 times the amount of non-hemoglobin iron in the circulation at any time. Transferrin is the shuttle for this traffic. Since the half-life in serum iron bound to transferrin is 1-2 hr while the half-life of the protein is about 7-8 days (51), the protein must be conserved during its interaction with the immature red cell and re-... 

The hematopoietic system is affected by both short- and long-term arsenic exposure. Arsenic is known to cause a wide variety of hematological abnormalities like anemia, absolute neutropenia, leucopenia, thrombocytopenia, and relative eosinophilia - more common than absolute esino-philia, basophilic stippling, increased bone marrow vascularity, and rouleau formation (Rezuke et al, 1991). These effects may be due to a direct hemolytic or cytotoxic effect on the blood cells and a suppression of erythropoiesis. The mechanism of hemolysis involves depletion of intracellular GSH, resulting in the oxidation of hemoglobin (Saha et al, 1999). Arsenic exposure is also known to influence the activity of several enzymes of heme biosynthesis. Arsenic produces a decrease in ferrochelatase, and decrease in COPRO-OX and increase in hepatic 5-aminolevulinic acid synthetase activity (Woods and Southern, 1989). Subchronic... 

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