Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0039730 (thalassemia)
 10,305 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Interaction of acetylphenylhydrazine with oxyhemoglobin A in a hemolysate or in intact red cells resulted in the formation of ferrihemochromes as shown by a characteristic optical spectrum. The same optical spectrum was observed in a suspension of red cell ghosts containing numerous Heinz bodies. Electron paramagnetic resonance of actylphenylhydrazine-incubated red cells disclosed the presence of previously identified reversible ferrihemochromes, which can be reduced to functional hemoglobin, and irreversible ferrihemochromes, which cannot be reduced to functional hemoglobin. (Ferrihemochromes are defined as low spin forms of ferric hemoglobin having heme ligands endogenous to the protein structure). In contrast, only irreversible ferrihemochromes could be observed in ghosts containing Heinz bodies. In addition both optical and magnetic features of sulfhemoglobin were observed in an acetylphenylhydrazine-treated red cell hemolysate. Similar optical features are produced by the interaction of aromatic nitrogen-containg reductants with purified oxyhemoglobin in the presence of (NH4)2S. This reaction is not effected by the presence of catalase, suggesting that H2O2 is not an intermediate of the reaction. It is concluded that the mechanism of action of acetylphenylhydrazine with oxyhemoglobin is two-fold, ultimate reduction to high spin ferric hemoglobin followed by ferrihemochrome formation. Thus it appears that the pathway of denaturation of hemolytic anemias and thalassemia or induced by chemical reagents, entails a common route involving the formation of ferric hemoglobin by a reductive mechanism, followed by reversible ferrihemochromes, irreversible ferrihemochromes, and ultimately, precipitation.
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PMID:The demonstration of ferrihemochrome intermediates in heinz body formation following the reduction of oxyhemoglobin A by acetylphenylhydrazone. 16 36

Superoxide ions (O2-) oxidized oxyhaemoglobin to methaemoglobin and reduced methaemoglobin to oxyhaemoglobin. The reactions of superoxide and H2O2 with oxyhaemoglobin or methaemoglobin and their inhibition by superoxide dismutase or catalase were used to detect the formation of superoxide or H2O2 on autoxidation of oxyhaemoglobin. The rate of autoxidation was decreased at about 35% in the presence of both enzymes. The copper-catalysed autoxidation of Hb (haemoglobin) was also shown to involve superoxide production. Superoxide was released on autoxidation of three unstable haemoglobins and isolated alpha and beta chains, at rates faster than with Hb A. Reactions of superoxide with Hb Christchurch and Hb Belfast were identical with those with Hb A, and occurred at the same rate. Hb Koln contrasted with the other haemoglobins in that the thiol groups of residue beta-93 as well as the haem groups reacted with superoxide. Haemichrome formation from methaemoglobin occurred very rapidly with Hb Christchurch and Hb Belfast, as well as the isolated chains, compared with Hb A. The process did not involve superoxide production or utilization. The relative importance of autoxidation and superoxide production compared with haemichrome formation in the haemolytic process associated with these abnormal haemoglobins and thalassaemia is considered.
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PMID:Reactions involving superoxide and normal and unstable haemoglobins. 18 28

The effect of H2O2 on ferrous human haemoglobin subunits (alphash-, betash-, alphapmb- and betapmb-chains) was studied. These chains were easily transformed to haemichrome by the addition of H2O2 or H2O2-generating systems, including glucose oxidase (EC 1.1.3.4) AND XANTHINE OXIDASE (EC 1.2.3.2), and this was ascertained by e.p.r. measurements and by absorption spectra. The changes in these haemoglobin subunits were not inhibited by superoxide dismutase (EC 1.15.1.1), but were decreased by catalase (EC 1.11.1.6). The rate of oxidation of alphapmb-chains was higher than that of alphash-chains, and the rate of oxidation of betapmb-chains was higher than that of betash-chains. Haemichrome was demonstrated to be formed directly from these ferrous chains by the attack by H2O2, and this process did not involve formation of methaemoglobin. On the basis of these findings the kinetics of the reaction between the haemoglobin subunits and H2O2 was studied, and the pathological significance of H2O2 in disorders of erythrocytes such as thalassaemia was discussed.
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PMID:Haemichrome formation from haemoglobin subunits by hydrogen peroxide. 20 62

Erythrocyte antioxidant enzymes, superoxide dismutase, catalase and glutathione peroxidase were found to be significantly high in subjects with alpha-thalassaemia and Hb Lepore trait, as a consequence of the increased oxidant stress which is known to exist in these conditions. Among the serum trace elements present in these enzymes, selenium was increased in subjects with Hb Lepore trait and significantly low in those with alpha-thalassaemia trait, while selenium erythrocyte content was significantly increased in alpha-thalassaemic subjects.
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PMID:Antioxidant system and serum trace elements in alpha-thalassaemia and Hb Lepore trait. 365 68

The activities of erythrocyte antioxidative enzymes were measured in two groups of patients with different genotypes of haemoglobin (Hb) H disease: 21 with alpha-thalassaemia 1 or alpha-thalassaemia 2 (alpha-thalassaemia 1/2) and 21 with alpha-thalassaemia 1/Hb Constant Spring (HbCS). They were compared with 21 normal subjects. Both genotypes of Hb H disease had increased activities of erythrocyte superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and catalase when compared with those of controls. Comparison of the two genotypes showed that subjects with alpha-thalassaemia 1/Hb CS, the more severe disease, had higher SOD and GSH-Px activities but lower catalase activity than those with alpha-thalassaemia 1/2. This indicates that there are compensatory mechanisms in Hb H erythrocytes to cope with increased generation of oxygen free radicals as a result of increased excess beta chain.
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PMID:Comparison of erythrocyte antioxidative enzyme activities between two types of haemoglobin H disease. 380 16

Comparisons were made of drug-induced oxidation of purified hemoglobins A, S, E, and F. Repetitive spectral scans of reaction mixtures containing menadione showed that Hb E was the most reactive and Hb F was the least reactive of the hemoglobins studied. Hb E oxidation was only slightly faster than normal, but it produced much larger relative quantities of low-spin ferric hemoglobin (hemichromes). Hb F oxidation was considerably slower than normal but produced normal amounts of hemichromes relative to methemoglobin. Precipitation occurred in the order E greater than S greater than A greater than F. The abnormally slow rate of Hb F oxidation was even more striking when the oxidant was acetylphenylhydrazine (APH), and the sensitivity of the reaction to catalase was severely diminished. These hemoglobins thus exhibit entirely different reaction profiles during drug-induced oxidation. The amino acid substitution in Hb E alters the globin tertiary structure, so that hemichromes can more readily form, whereas the decreased susceptibility to oxidative denaturation of Hb F appears related to the absence of a site that normally reacts with hydrogen peroxide to increase oxidation rate. Such Hb F stability is consistent with the mild phenotypic expression of doubly heterozygous beta-thalassemia/HPFH and Hb S/HPFH. The role of Hb E instability in altered red cell morphology relative to the thalassemia-like deficit of beta globin mRNA has not been entirely resolved. Nevertheless, the clinical repercussions of the abnormal properties of Hb E are mild, and they may be involved with the prevalence of this hemoglobin in Southeast Asia as a balanced polymorphism in which the advantage to heterozygotes is, as yet, unclear.
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PMID:Differences in the reaction sequences associated with drug-induced oxidation of hemoglobins E, S, A, and F. 619 77

Hemoglobin fractions were studied in 80 patients suffering from nephroblastoma (Wilms' tumor). 10 out of 80 children had an elevated fetal hemoglobin value, higher than 2.5%, but as there was no other evidence for a thalassemia, we could not refer these patients to delta beta-thalassemia heterozygotes. An electrophoretic study of hemolyzates showed that 4 children had a uniform "quickly-proceeding" anomalous hemoglobin fraction localized in front of HbA2 which decreased in time. In one case, this anomaly was discovered in propositus and also in his father and paternal grandmother. A child suffering from unilateral sporadic Wilms' tumor and his mother had a Negro type hereditary persistence of fetal hemoglobin (HPHF). This complex of Wilms' tumor and HPHF is described for the first time. HPHF and nephroblastoma complex as a possible variant of intersticial deletion of the short arm of chromosome 11 is discussed. The diagnostic value of the study of hemoglobin fractions and the activity of enzymes (catalase, LDH-A), whose genes are localized on the short arm of chromosome 11, are also discussed. It would be useful for genetic counselling to select a group of children with high risk for nephroblastoma.
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PMID:[Changes in the hemoglobin fractions of nephroblastoma patients]. 620 Mar 83

Glucose-6-phosphate dehydrogenase (G-6-PD) deficient erythrocytes are particularly sensitive to oxidant stress. In order to evaluate if these cells are protected against oxidant damage, we assayed the antioxidant enzymes superoxide dismutase (SOD), catalase and glutathione peroxidase (GSH-Px) in erythrocytes of G-6-PD deficient (hemizygous and heterozygous) subjects. Normal levels of antioxidant enzymes were found in all subjects examined both with positive and negative histories of haemolytic crisis after fava bean or drug ingestion. In contrast, high levels of catalase and GSH-Px were found in a small group of G-6-PD deficient subjects (hemizygous and heterozygous) with beta-thalassaemia trait, probably by reason of the chronically enhanced oxidant stress which is present in beta-thalassaemia.
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PMID:Erythrocyte superoxide dismutase, catalase and glutathione peroxidase in glucose-6-phosphate dehydrogenase deficiency. 713 87

The activities and subcellular distribution of enzymes implicated in the protection of cells from free-radical mediated damage were determined in liver biopsy specimens from control and iron-overloaded patients. 2. There was a small but insignificant decrease in the activity of glutathione reductase in patients with secondary iron overload due to multiple transfusion therapy for thalassaemia major. 3. The activities of superoxide dismutase, catalase and glutathione peroxidase were similar in both patient groups. 4. Subcellular fractionation studies indicated a major cytosolic localization of these enzymes with a minor mitochondrial component. The relative proportions of the enzymes in the two locations was similar in both control and iron-overloaded patients. 5. Approximately 80% of the hepatic glutathione was present in the reduced form in both patient groups and it is concluded that although free-radical mediated damage might be implicated in the pathogenesis of tissue damage due to iron overload no significant defect in these protective mechanisms can be demonstrated.
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PMID:Activities of some free-radical scavenging enzymes and glutathione concentrations in human and rat liver and their relationship to the pathogenesis of tissue damage in iron overload. 736 62

The 'antioxidant' enzymes superoxide dismutase (SD), catalase and glutathione peroxidase (GSH-Px) were found greatly elevated in red blood cells of subjects with beta-thalassaemia minor and similar to normal values in red blood cells of subjects with beta-thalassaemia major. These findings allows us to speculate that red cells in beta-thalassaemia minor react to the increased oxidant threat with augmented antioxidant enzyme activities. The normal levels of antioxidant enzymes in beta-thalassaemia major seem to be due to the presence of normal red cells owing to multiple transfusions.
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PMID:Erythrocyte superoxide dismutase, catalase and glutathione peroxidase activities in beta-thalassaemia (major and minor). 744 78


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