Y-Globin chain

Hb Bart s. Hb Bart s results from deletion of aU four a-globin genes with the subsequent inability to produce any a-globin chains that leads to failure of synthesis of Hbs A, F, or A2. In the fetus there is an excess of y-globin chains that join together to form unstable tetramers known as Hb... 

The continued absorption of iron causes its deposition in various tissues starting with liver and spleen and followed by myocardium. Deposition of iron in the myocardium usually results in death by intractable cardiac failure. Patients suffer from hypoparathyroidism and hypogonadism. Patients with the severe form of thalassemia are more susceptible to bacterial infection, possibly due to the increase in serum iron, which may favor bacterial growth. Iron overload is less common in the adult forms of Q -thalassemia. This is most likely the result of a fundamental difference between a and -thalassemia. As mentioned, the excess of Q -globin chains cannot form viable tetramers and causes red-cell destruction. The excess jS-chains present in a-thalassemia are able to form solnble homodimers and do not precipitate in the bone marrow. This is paralleled in the fetal state when excess y-chains form solnble homodimers. Hence, a-thalassemia is characterized by a severe degree of inefficient erythropoiesis and a milder degree of anemia. 

Fig. 12. The separation of globin chains prepared from cells incubated with leucine- H by chromatography on a column of CM-cellulose. Solid line represents the optical density at 280 nm, and the dotted line, the radioactivity. (A) A normal subject the P chain is eluted in tubes 20-30 and the a chain in tubes 42-52. The a p ratio of radioactivity is 1.0. (B) A patient with /3-thalassemia major the y chain is found in tubes 10-20, the p chain in tubes 22-32, and tiie a chain in tubes 38-50. The a. p ratio of radioactivity is greater than 60. (C) A patient with Hb-S-/3-thalassemia the normal p chain is found in tubes 25-33, the p chain in tubes 35-42, and the a chain in tubes 46-55. The a -P ratio of radioactivity is 2.9. From Marks and Bank (M7) with permission of the authors and publisher.

Sugano M, Hidaka H, Yamauchi K, Nakabayashi T, Higuchic Y, Fujita K, et al. Analysis of hemoglobin and globin chain variants by a commonly used capillary isoelectric focussing method. Electrophoresis 2000 21 3016-9. 

A. Jacquet, T. Kleinschmidt, T. Dubois, A. G. Schnek, Y. Looze, and G. Braunitzer. The thiol proteinases from the latex of Carica papaya L. IV. Proteolytic specificities of chymopapain and papaya proteinase omega determined by digestion of alpha-globin chains. Biol. Chem. Hoppe-Seyler 370 819 (1989). 

Inoue H, Maeno Y, Iwasa M, et al. (1997) Sensitive detection of human globin chains by microbore high-performance liquid chromatography and its forensic applications. Journal of Chromatography B, Biomedical Sciences Applications 688 221-227. 

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... 

Regulation at the translational level can also affect Hb synthesis. It is known that globin chain synthesis is reduced when heme and its precursors (ferrum) are absent. The addition of ferrum to reticulocytes stimulates Hb synthesis. Moreover, the a-chains are not released from the polysomes until the jS-chains are synthesized (Baglioni, 1966 Colombo and Baglioni, 1966). Also, the composition of methionine and leucine tRNA populations differs in embryonic and adult reticulocytes of chickens. It is possible that the transition from y to P polypeptide synthesis occurs at the translation level and depends upon the composition of the tRNA pop-... 

Fetal hemoglobin (HbF) HbF is a tetramer consisting of two a chains identical to those found in HbA, plus two gamma (y) chains (0272, see Figure 3.13). The y chains are members of the p-globin gene family (see p. 35). 

In thalassemias of the jS-globin gene family, there is reduced synthesis of chains, with or without reduced synthesis of y or 5 chains. An isolated decrease in y- or 5-globin synthesis would probably be benign and likely to be detected only by chance. Hemoglobin Lepore is usually included with the jS-thalassemias, since synthesis of normal chains is reduced or absent. 

The y- and 5-chain mutants are difficult to study because of the small fraction of HbF and HbA2 present in adult erythrocytes. Overt clinical symptoms associated with y- and 5-chain variants are rare. By routine screening, 14 5-globin variants have been discovered but are of no clinical consequence. Thirty-five mutant y sequences (involving the Gy or the Ay chains) have been identified. They are all benign except for HbF Poole [Gyl30(H8) Tyr —> Gly], an unstable hemoglobin that causes hemolytic disease in the newborn. 

Figure 12-1. Maturation of hemoglobin from the fetal form to the adult form. In P-thalassemias, because of a defect in the p-globin gene, the y-chain cannot be effectively replaced with the p-chain.

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