Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0019045 (hemoglobinopathies)
 2,704 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We believe that on the basis of all available data, severe oxidative damage occurs in alpha- and beta-thalassemic RBCs, as depicted schematically in Fig 6. The differences in the severity and pattern of the oxidative damage may be related to the type and, perhaps, quantity of precipitated globin chains. The detrimental effect of the excess chains is multifold. In the process of globin-chain precipitation, free radicals are generated. The end product of the precipitated hemoglobin chains is heme, from which eventually iron and globin are liberated. Globin chains have been found to interact and disrupt the RBC membrane, damaging the cytoskeleton. The role of heme has not yet been studied in detail in thalassemic RBCs. However, there is some evidence that it participates in damaging RBCs in other types of hemoglobinopathies. Excess of iron is known to be a catalyst of peroxidation via the Fenton reaction, causing damage to the various RBC membrane components (lipids, proteins, etc). The denatured hemaglobin, in the form of hemichromes, aggregates with protein 3, forming Actual proof of excessive free radical production in thalassemia is still warranted. It will not be easy to document since the amount of superoxide dismutase in RBCs is above and beyond that required for neutralizing excess amount of superoxide. The more active radicals, particularly hydroxyl free radical, are difficult to measure because they are so active an interact immediately with any given substrate in their vicinity. In addition, we have to better understand the finding of excess membrane lipids in thalassemic RBCs and whether there are changes in the formation and propagation of lipid peroxidation in these cells compared with normal RBCs. Regarding the proteins, further understanding is required concerning the exact type and sites of oxidation that occurs in the beta-thalassemia 4.1 protein, and whether the damage found in alpha-thalassemia is due to oxidation of ankyrin itself or its entrapment within the complex of the precipitated hemichromes of beta chains. What is the role of the different globin chain oxidation and precipitation in generating such different cytoskeletal protein alterations? Another point that needs to be elucidated is the role of different kinds of antibodies that are attached to the newly exposed antigenic sites on the thalassemic RBC membranes.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Oxidative denaturation of red blood cells in thalassemia. 240 97

Unstable hemoglobin disorders are due to substitutions or deletions of amino acids which alter the normal tertiary structure of hemoglobin and/or decrease heme-binding to globin. These changes result in enhanced oxidation to methemoglobin, rapid conversion of methemoglobin to hemichrome and sometimes heme loss, which leads to denaturation and precipitation as Heinz bodies. This process is associated with marked oxidative membrane damage, such as crosslinking of membrane proteins, membrane lipid peroxidation, hemin-induced destabilization of cytoskeletal protein interactions, and increased permeability to potassium ions. The damaged erythrocytes are sequestered in the spleen, where Heinz bodies are "pitted" or the entire cell is phagocytized by macrophages. The precise mechanisms leading to hemolysis are not fully understood. However, one hypothesis involves hemichrome binding to the cytoplasmic domain of band 3, leading to clustering of band 3 in the membrane and immunologic recognition of the redistributed band 3 by autologous senescent antibodies. This theory is based on immunologic findings rather than deformability changes, and it is consistent with many features of unstable hemoglobins.
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PMID:[Effects of abnormal Hb on red cell membranes]. 1022 88