Haemoglobin synthesis

The most popular bioassay of EPO involves a mouse-based bioassay (EPO stimulates red blood cell production, making it useful in the treatment of certain forms of anaemia Chapter 10). Basically, the EPO-containing sample is administered to mice along with radioactive iron (57Fe). Subsequent measurement of the rate of incorporation of radioactivity into proliferating red blood cells is undertaken. (The greater the stimulation of red blood cell proliferation, the more iron taken up for haemoglobin synthesis.)... 

Physiologically, body stores are maintained by extracting approximately 10% of the iron provided in a balanced diet and this corresponds to 1.5 mg each day for males and slightly more for females to compensate for pregnancy and menses. The trace element is derived from food by peptic digestion and after reduction the ferrous form crosses the enterocyte to be released at the serosal pole via the ferroportin-hepcidin mechanism to be transported, by plasma transferrin, to developing red cells in the marrow for haemoglobin synthesis. At the end of their life span effete erythrocytes are removed by the reticuloendothelial system in the spleen, bone marrow and the liver. 

C. May, S. Rivella, J. Callegari, G. Heller, K. M. L. Gaensler, L. Luzzatto, and M. Sadelain, Therapeutic Haemoglobin Synthesis in p-Thalassaemic Mice Expressing Lentivirus-Encoded Human p-Globin, Nature 2000,406, 82. 

Non-thresholded chemicals that are not carcinogens are less frequently identified. For many years lead was considered to be thresholded because its effects on haemoglobin synthesis were not seen at low doses. However, recent work into the effects of lead on mental development suggest that there may be no threshold for this end-point. Food is a relatively minor source of lead exposure compared with air and dust in urban environments. For chemicals that relate to toxicological end-points that do not show thresholds it is not possible to identify a NOAEL or PTWI. In such cases it is desirable to estimate the level of risk associated with a given level of exposure. 

Blastoderm Birds only Embryonic Haemoglobin synthesis... 

Spleen, liver, blastoderm 5/3-DHT 5/3-Reductase Haemoglobin synthesis The response does not primarily involve genetic transcription... 

Manganese ions, Mn2+ Present in some enzymes, it activates blood haemoglobin synthesis, urea formation, growth, reproduction processes and release of insulin. Manganese ions also take part in enzyme control in the brain Zinc ions, Zn2+ Small quantities help carbon dioxide metabolism and removal. Zinc is... 

Q2 Amino acids are needed to produce the plasma membrane Bi2 (cyanocobal-amine), which is stored in the liver, is required for synthesis of DNA. Folic acid is also needed for synthesis of DNA (it is a component of thymine, adenine and guanine) and for RNA synthesis. Other B vitamins are required for haem synthesis and oxidative metabolism. Iron is required in ferrous form for haemoglobin synthesis vitamin C helps maintain iron in its ferrous form. 

Q4 When the supply of iron is greatly diminished, haemoglobin synthesis is restricted. Erythropoiesis continues and is controlled by erythropoietin from the kidney. Release of this hormone is increased in anaemia, in response to a reduced concentration of circulating haemoglobin. The bone marrow will then be stimulated to produce more red cells, but of smaller size and with smaller haemoglobin content a blood film may show red cells of unequal sizes this is known as anisocytosis. 

Q4 The water-soluble vitamins (B and C) and essential minerals, such as iron, are absorbed in the small intestine. The reabsorption of iron in the duodenum and proximal jejunum involves a complex active transport process. When there is a large reduction in the surface area of this part of the gut, there is a marked reduction in reabsorption of iron (and B vitamins). Haemoglobin synthesis is decreased, leading to development of anaemia, which is a common symptom in celiac disease. 

Microcytic anaemia is primarily a result of a failure or deficiency of haemoglobin synthesis, which may be caused by several aetiologies ... 

Gaburro, D., Volpato, S., and Vigi, V., Diagnosis of beta thalassaemia in the newborn by means of haemoglobin synthesis. Acta Paediat. Scand. 59, 523-528 (1970). 

Normal haemoglobin has a Pjg of 3.4 kPa and n of 2.6-3.0 at pH 7.4. Values of both P50 and n are affected by genetic abnormalities in haemoglobin synthesis that alter the amino acid sequence. Over 190 such variants are known, with a wide range of Pjg and n values. 

May C, Rivella S, Callegari J, Heller G, Gaensler KM, et al. 2000. Therapeutic haemoglobin synthesis in beta-thalassae-mic mice expressing lentivirus-encoded human beta-globin. Nature 406 82-86... 

Effective haemoglobin synthesis and red blood cell production also depends on the action of a growth factor, erythropoietin, produced by the kidneys. In chronic renal failure lack of this growth factor results in anaemia. Replacement therapy is by intravenous or subcutaneous injection of epoetin. 

Housman, D., M. Jacobs-Lorena, U. L. Rajbhandary, and H. F. Lodish. 1970. Initiation of haemoglobin synthesis by methionyl-tRNA. Nature (London), 227 913. 

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