Globin chains from blood

Masala and Manca [1269] characterized and identified globin chains from red blood cells with RP HPLC using a wide pore C4 column (X = 220 nm) and an 80-min 20/80-> 60/40 acetonitrile/water (0.1% TEA) gradient. Blood sample lysates were analyzed. The general elution order was heme < pce-fi < P < d < a < y < < yj. Variants such as (, Sp, a, and y were also... 

These tests use either heat or isopropanol to precipitate the unstable Hb and must be performed on fresh blood. There are more than 100 unstable Hbs resulting mainly from the interchange of nonpolar amino acid residues for polar amino acid residues in positions in either the a- or P-globin chain associated with the heme cleft. Hb Hasharon (a47(CD) P ), an Hb variant found in Ashkenazi Jews,... 

One or more abnormal a-globin chains can combine with Hb S. In African-Americans and West Africans the combination of Hb G Philadelphia (a68(E17) " > ) with Hb S is prevalent. HPLC analysis (Figure 31-12, i) on blood samples from these individuals shows at least two major peaks and two smaller peaks. The two major peaks are due to the combination of the normal a-chain with the normal P-chain and the abnormal a-chain with the normal P-chain. The two smaller peaks are due to the combination of the normal a-chain with the abnormal P-chain and the abnormal a-chain with the abnormal P-chain. Electrophoresis at alkaline pH shows major bands in the A and S positions with a minor band in the C position. At acid pH, bands are seen in the A and S positions. CBC analysis gives a slightly decreased Hb level with normal MCV and MCH. a- or p-thalassemia can be co-inherited with Hb G Philadelphia and Hb S. In these cases, CBC analysis results in markedly decreased MCV and MCH with reduced Hb concentration. 

Characteristics of the more common /3-thalassemia syndromes are summarized in Table 28-4. Not included are two different abnormal heterozygotes. Anemia results from precipitation of excess a-globin chains, premature red cell destruction in bone marrow and the circulation, and deficiency of functional hemoglobin tetramer. /S-Thalassemia major, or Cooley s anemia, occurs when /3-globin synthesis is markedly depressed or absent. The ineffective erythropoiesis causes massive erythroid proliferation, skeletal deformities, and extramedullary erythropoiesis. The usual treatment is frequent blood transfusion. 

Phagocytic breakdown destroys older blood cells, primarily in the spleen, but also in the marrow (Fig. 99-2). Amino acids from the globin chains return to an amino acid pool heme oxygenase acts on the porphyrin heme structure to form biliverdin and to release its iron. Iron returns to the iron pool to be reused while biliverdin is further catabolized to bilirubin. The bilirubin is then released into the... 

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