Synthesis globin chain

Fig. 5. The switch in human globin chain synthesis at birth.

B68. Braverman, A. S., and Bank, A., Changing rates of globin chain synthesis during erythroid cell maturation in thalassemia. J. Mol. Biol. 42, 57-64 G969). 

P-Thalassemia major results from mutations that interfere with translation or are involved in the initiation, elongation, or termination of globin chain synthesis. Mutations that interfere with translation account for almost 50% of ail die p-thalassemia mutations. Included in this are frame shift or nonsense mutations that produce premature termination codons that result in incomplete translation of the P-globin gene and nonproduction of the P-globin chain resulting in P -thalassemia. 

The thalassemias are classified according to which chains are deficient. The most important types are the a- and /8-thalassemias. In each type, globin chain synthesis may be reduced ( +, /T ") or absent (a°, /3°). By the use of probes to detect the presence or absence of specific globin genes, thalassemias due to deletion of globin genes have been distinguished from nondeletion varieties. (5-, 3-/8-, and j/-3-/8-Thalassemias are extremely rare. 

Figure 3. Globin chain synthesis in the immature blood cells of an adult with no globin abnormality (top), a patient with Cooley s anemia (middle), arid a newborn with no globin abnormality (bottom) for experimental details see Ref. 7...

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-... 

Circulating RBCs lack the enzymes to produce either haem groups or globin chains so the synthesis of haemoglobin is a defining feature of early RBC maturation. Globin chain production is like the formation of any other protein, but a and 3 chain synthesis is closely linked with haem synthesis. 

The thalassemias are hereditary hemolytic diseases in which an imbalance occurs in the synthesis of globin chains. As a group, they are the most common single gene disorders in humans. Normally, synthesis of the a- and p-globin chains are coordinated, so that each a-globin chain has a p-globin chain partner. This leads to the forma... 

Thalassemias are hereditary hemolytic diseases in which an imbalance occurs in the synthesis of either a or 3 globin chains. Each thalassemia can be classified as either a disorder in which no globin chains are produced (a0- or p°-thalassemia), or in which some chains are synthesized but at a reduced rate (a+- or p+-thalassemia). [Note In p-thalassemias, synthe sis of p globin chains is decreased or absent, whereas in a-thalassemias, synthesis of a globin chains is decreased or absent.]... 

R18. Rieder, R. F., Synthesis of hemoglobin Gun Hill increased synthesis of the heme-free jS globin chain and subimit exchange with a free a-chain pool. J. Clin. Invest. 50, 388-400 (1971). 

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... 

Changes in human globin chain concentration during development. [Reproduced with permission from W. G. Wood, Hemoglobin synthesis during human fetal development. Br. Med. Bull. 32, 282 (1976).]... 

The thalassemias are a heterogeneous group of hypochromic, microcytic anemias caused by unbalanced synthesis of globin chains. In Southeast Asia, the Philippines, China, the Hawaiian Islands, and the Mediterranean countries, thalassemia syndromes are relatively common and... 

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. 

The term hemoglobinopathies refers to hemoglobin disorders caused by normal synthesis of qualitatively abnormal globin chains. Transcription and translation of mutant genes usually proceed at a normal rate, but the products denature rapidly or function abnormally. 

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