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)

The mass concentrations of whole blood reduced glutathione and catalytic activity concentrations of the enzymes, glucose-6-phosphate dehydrogenase (EC 1.1.1.49), glutathione reductase (EC 1.6.4.2) and glutathione peroxidase (EC 1.11.9) were analysed in 25 cases of homozygous beta-thalassaemia, 20 cases of heterozygous beta-thalassaemia and 10 controls. The results showed a significant elevation of reduced glutathione and enzymes of the pentose phosphate pathway in homozygous beta-thalassaemia, indicating the existence of an enzyme-regulated glutathione turnover system in the overt state to combat the augmented red cell membrane damage due to auto-oxidant threat. However, in heterozygous beta-thalassaemia, reduced glutathione was increased, but there was no similar elevation of enzymes except for glutathione peroxidase.
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PMID:Enzymes of the pentose phosphate pathway in glutathione-regulated membrane protection in beta-thalassaemia. 144 62

FAD-dependent methaemoglobin reductases (MHR) were studied in red cells in heterozygous beta-thalassaemia to investigate how they related to low FAD-dependent glutathione reductase (GR). In contrast to GR, MHR activities were usually normal or increased. In particular, whether expressed in relation to haemoglobin or number of red cells, NADPH-MHR activity was markedly increased in most subjects, probably being a response to increased oxidative stress. Oral riboflavin had no effect on MHR activities, indicating saturation with FAD even though GR was deficient. A strong correlation between percent stimulation of GR by FAD and NADPH-MHR activity indicates that FAD is utilized by MHR at the expense of GR. This could be an important influence on GR in heterozygous beta-thalassaemia. Thus, the low activity resulting from an inherited deficiency of FAD is decreased further.
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PMID:Utilization of red-cell FAD by methaemoglobin reductases at the expense of glutathione reductase in heterozygous beta-thalassaemia. 204 24

Generally, individuals who are heterozygous to haemoglobin S (Hb AS) are asymptomatic and do not present any haematological or clinical manifestations. However, other associated genetic abnormalities may influence the presentation in Hb AS cases. This study was conducted on twenty children heterozygous for HB S who presented clinical manifestations similar to those of sickle cell anaemia. All these children had anaemia associated with several red cell morphological abnormalities. The white blood cell counts were elevated in all patients and differential count studies showed a substantial increase in lymphocytes and polymorphonuclear leucocytes in the majority of the cases. Forty-five per cent of the patients had associated alpha-thalassaemia, 60 per cent had beta-thalassaemia, 30 per cent had G-6-PD deficiency and 10 per cent had partial glutathione reductase deficiency. Pyruvate kinase activity was normal in all cases. Riboflavin deficiency was encountered in 30 per cent of the patients and iron deficiency in 15 per cent of these Hb S heterozygotes. The major clinical findings were splenomegaly, hepatomegaly, and vaso-occlusive crisis. The majority of the patients had received blood transfusions. The hand and foot syndrome was identified in three (15 per cent) of the patients. The haematological and clinical findings in these twenty Hb S heterozygotes are presented in this paper and the possible causes for these abnormalities are discussed.
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PMID:Case studies on haemoglobin S heterozygotes with severe clinical manifestations. 228 93

In 18 beta-thalassaemia families from the Ferrara area the incidence of an inherited low flavin mononucleotide (FMN)-dependent pyridoxine phosphate (PNP) oxidase activity, a sensitive indicator of red-cell FMN deficiency, is higher in related members in these families than in the unrelated spouses and controls subjects without family history of thalassaemia. This suggests slower red-cell riboflavin metabolism in thalassaemia families, which may have resulted from selection in combination with thalassaemia by malaria. However, there was a markedly higher incidence of red-cell flavin adenine dinucleotide (FAD) deficiency in thalassaemia heterozygotes than in their normal relatives. This was indicated by higher stimulation of FAD-dependent glutathione reductase (GR) activity by FAD and lower GR activity per red cell, and suggests a marked additive effect by thalassaemia on the red cell FAD deficiency that results from the inherited slow riboflavin metabolism. There is evidence that diversion of FAD to other FAD-dependent enzymes might be an important factor.
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PMID:Genetic and other influences on red-cell flavin enzymes, pyridoxine phosphate oxidase and glutathione reductase in families with beta-thalassaemia. 272 60

Certain aspects of the metabolism of centrifuged young and old erythrocytes in hemoglobin H disease have been examined and compared with similar studies of beta thalassemia and normal cells. Glycolysis, hexose monophosphate shunt activity (HMPS), potassium flux, and glutathione (GSH) content were measured. The distributions of hemoglobins H and F, as well as the activities of erythrocyte glucose-6-phosphate dehydrogenase (G6PD) and glutamic oxalacetic transaminase (GOT), were utilized for estimations of the relative ages of the cell samples. The young erythrocytes in hemoglobin H disease differed in several respects from older hemoglobin H cells. They contained more soluble hemoglobin H and GSH and, after splenectomy, fewer inclusions. HMPS activity was subnormal in hemoglobin H young cells and rose to normal activity in old cells. Potassium flux tended to increase in old cells when inclusions were present.Beta thalassemia young cells contained less hemoglobin F and, after splenectomy, more inclusions than old cells. In addition, they had markedly increased glycolysis and HMPS activity. GSH was randomly distributed. Potassium flux was increased in younger cells and particularly increased when inclusions appeared in younger cells after splenectomy. The results are interpreted to indicate that inclusion formation is associated with increased erythrocyte cation permeability in the thalassemia syndromes. This is not related to the level of intracellular GSH. The decreased HMPS activity in young hemoglobin H cells may be due to the presence of the extra thiols of soluble hemoglobin H which can act as a reducing agent. The substitution of hemoglobin H for glutathione in this capacity would then spare the NADPH-requiring glutathione reductase system. As a consequence, HMPS activity would decline. However, in older cells the oxidized hemoglobin H precipitates; these must rely upon GSH and glutathione reductase activity for thiol reduction capacity. Accordingly, HMPS activity increases to normal in the old cell population.
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PMID:Influence of hemoglobin precipitation on erythrocyte metabolism in alpha and beta thalassemia. 576 25

The activity of 18 red blood cell (RBC) enzymes and reduced glutathione (GSH) content were measured in 70 normal subjects, in 50 heterozygous beta-thalassaemia carriers and in 50 non-thalassaemic patients with haemolytic anaemia and high reticulocyte counts. In addition, pyrimidine 5'nucleotidase (P5N) activity was also determined in 34 patients with hypochromic, microcytic, iron deficiency anaemia. beta-Thalassaemia trait was associated with an increase in almost all of the enzyme activities, except for 2,3-bisphosphoglycerate synthetase (BPGS) and glutathione reductase (GR) which were normal and for acetylcholinesterase (AChE) and P5N which were slightly and markedly decreased respectively. The increases in enzyme activities were similar to those observed in patients with non-thalassaemic reticulocytosis except for glyceraldehydephosphate dehydrogenase (GAPD), phosphoglyceratekinase (PGK), pyruvate kinase (PK), glutathione peroxidase (GPX) and adenylate kinase (AK) which were higher than in non-thalassaemic group of patients with increased number of reticulocytes. No correlation was found between the severity of P5N deficiency and the intensity of basophilic stippling which was present in 46 of 50 thalassaemic carriers here studied. In addition, GSH content and UV absorption spectra of deproteinized thalassaemic RBC extracts were also found to be normal. The present findings provide further information on the metabolic status of RBC in beta-thalassaemia trait and suggest a possible molecular explanation for the frequently observed basophilic stippling in this disease.
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PMID:Pyrimidine 5'nucleotidase and several other red cell enzyme activities in beta-thalassaemia trait. 632 Aug 62

It was demonstrated in heterozygous alpha 1- and beta-thalassaemia, that the slow rate of red-cell metabolism of vitamin B6, previously shown to be inherited, is regulated by the FMN-dependent pyridoxine (pyridoxamine) phosphate oxidase, as in control subjects. In this study, 60% of the patients with thalassaemia had a low B6 oxidase activity. An inverse correlation with the stimulation of the FAD-dependent glutathione reductase activity by FAD confirmed that red-cell riboflavin status was responsible. The inherited nature and lack of signs of nutritional riboflavin deficiency led to the conclusion that this was the result of a slow rate of red-cell metabolism of riboflavin. Stimulation of glutathione reductase activity by FAD correlated inversely with its basic activity in thalassaemia and control subjects. There was a high incidence of a low activity of this enzyme per red cell in patients with thalassaemia. The possibility that a low activity of glutathione reductase and a slow metabolism of B6 and riboflavin in the red-cell might play a part in the degree of severity of the thalassaemic disease is discussed.
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PMID:Low red cell activity of pyridoxine (pyridoxamine) phosphate oxidase and glutathione reductase associated with thalassaemia. 733 97

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

In two areas in Italy where malaria was endemic--in the Po delta and Maremma on the west coast--we have found a high prevalence of an inherited flavin-deficient red cell in the normal population, suggesting selection by malaria. This study in Sardinia enabled a direct comparison of red-cell activities of FAD-dependent glutathione reductase (EGR) and FMN-dependent pyridoxine phosphate (PNP) oxidase in an ethnically homogeneous population, between two coastal villages where malaria was endemic from 300 B.C. and two mountain villages with no history of malaria. Both enzyme activities were significantly lower on the coast, and it did not seem that this could be explained by possible small differences in dietary riboflavin. As was thought to be the case in Ferrara and Grosseto, it is probable that a genetically controlled flavin-deficient red cell was selected for by malaria. Low EGR apoenzyme activity was more common on the coast, usually explaining the accompanying low basic EGR activity, and may also have been selected for by malaria. This adds to evidence from others that the mechanism of defence of a flavin-deficient red cell against malaria may be through EGR deficiency. It could also play a part in the protection given by heterozygous beta-thalassemia. The multifactorial protection of the population against malaria is discussed.
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PMID:Deficiency of two red-cell flavin enzymes in a population in Sardinia: was glutathione reductase deficiency specifically selected for by malaria? 766 97

There is a high prevalence of a familial flavin-deficient red blood cell in Ferrara province in the Po delta in northern Italy, believed to have been selected for by malaria which was endemic from the 12th century. In the present study, activities of FAD-dependent red-cell glutathione reductase (EGR) in the Grosseto area of Maremma on the west coast of Italy where malaria was endemic from 300 B.C. are compared both with activities in the Ferrara area and with activities where there was no history of endemic malaria--in the Florence area and in London in people of Anglo-Saxon origin. EGR activities were similar in Grosseto and Ferrara and were significantly lower than in Florence and London. As previously found in Ferrara, low EGR activity in Grosseto was shown to be unrelated to low dietary riboflavin intake. These findings in Grosseto, suggesting selection by malaria, are particularly interesting because, unlike the situation in Ferrara and most other malarial areas, the prevalence of thalassemia and glucose-6-phosphate dehydrogenase deficiency is very low, and they do not appear to have been selected for in Maremma. It is possible that a flavin-deficient red cell, known to inhibit growth of the malaria parasite, was an important protecting factor in the population of this area over the centuries.
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PMID:Is the flavin-deficient red blood cell common in Maremma, Italy, an important defense against malaria in this area? 797 61


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