Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0002878 (hemolytic anemia)
 7,530 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The severity of enzyme deficiency often does not correlate well with the clinical severity of genetic diseases. Thus, some G6PD variants associated with severe enzyme deficiency, such as Union and Markham, cause no hemolytic problem, while some variants associated with less severe deficiency, such as Manchester, Alhambra, and Tripler, cause chronic hemolytic anemia. The kinetic characteristics of these variant enzymes have not explained the discrepancy. However, examination of the normal and variant enzymes under simulated physiologic conditions, with the effects of various intermediate metabolites and co-enzymes in red cells being taken into consideration, reveal that the G6PD's from hemolytic variant subjects are strongly inhibited by a physiologic concentration of NADPH because of their high Michaelis constant for NADP or low inhibition constant for NADPH, and they are more sensitive to inhibition by ATP. These variant enzymes cannot generate enough NADPH in red cells to maintain an adequate concentration of reduced glutathione. The nonhemolytic variant enzymes are far less sensitive to the inhibition by NADPH because of their low Michaelis constant for NADP and high inhibition constant for NADPH. The physiologic activity of these nonhemolytic variant enzymes is estimated to be more than 30 percent of the activity of the normal G6PD, and this activity is adequate to maintain the red cells unhemolyzed.
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PMID:Hemolytic anemia and G6PD deficiency. 440 5

Acetylsalicylic acid (ASA) is known to cause severe hemolytic anemia in some glucose-6-phosphate-dehydrogenase-deficient (G-6-PD-deficient) individuals. To study its mechanism, erythrocytes from an ASA-sensitive patient were transfused into a normal compatible recipient. The administration of 2,5-dihydroxybenzoic (gentisic) acid, a known ASA metabolite with redox properties, to the recipient resulted in a marked decrease in the survival of the patient's erythrocytes. Similar studies with red cells from individuals with A- and Mediterranean variants of G-6-PD revealed no alteration in the erythrocytes' survival. Further studies disclosed that both salicylate and gentisate competitively inhibited the G-6-PD from the ASA-sensitive patient resulting in a marked change in the K(m) for NADP. These drugs also inhibited the A- and Mediterranean variants of G-6-PD. The magnitude of inhibition, however, was comparatively small and not different from that observed with a normal enzyme. The above studies suggested that enzyme inhibition by salicylate and gentisate may play an important role in ASA-induced hemolysis. Such an inhibition would further curtail NADPH regeneration, rendering the cells more vulnerable to oxidants. In this connection, gentisate seems to play a major role in ASA-induced hemolysis for it is both a G-6-PD inhibitor and an "oxidant."
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PMID:Acetylsalicylic acid--induced hemolysis and its mechanism. 543 68

We evaluated the erythrocytes of two patients with hereditary pyrimidine 5'-nucleotidase deficiency. Significant findings included an increased reduced glutathione content, increased incubated Heinz body formation, a positive ascorbate cyanide test, and decreased intraerythrocytic pH. The pentose phosphate shunt activity of the patients' red cells as measured by the release of 14CO2 from 14C-1-glucose was decreased compared to high reticulocyte controls. Glucose-6-phosphate dehydrogenase (G6PD) activity in hemolysates from control erythrocytes was inhibited 43% by 5.5 mM cytidine 5'-triphosphate (CTP) and 50% by 5.5 mM in uridine 5'-triphosphate (UTP) at pH 7.1. CTP was a competitive inhibitor for G6P (Ki = 1.7 mM) and a noncompetitive inhibitor for NADP+ (Ki = 7.8 mM). Glutathione peroxidase, glutathione reductase, and 6-phosphogluconate dehydrogenase were not affected by these compounds. Pentose phosphate shunt activity in control red cell hemolysate at pH 7.1 was inhibited to a similar degree by 5.5 mM CTP or UTP. Since the intracellular concentrations of G6P and NADP+ are below their KmS for G6PD, these data suggest that high concentrations of pyrimidine 5'-nucleotides depress pentose phosphate shunt activity in pyrimidin 5'-nucleotidase deficiency. Thus, this impairment of the pentose phosphate pathway appears to contribute to the pathogenesis of hemolysis in pyrimidine 5'-nucleotidase deficiency hemolytic anemia.
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PMID:Hemolytic anemia in hereditary pyrimidine 5'-nucleotidase deficiency: nucleotide inhibition of G6PD and the pentose phosphate shunt. 628 44

Red cell glucose-6-phosphate dehydrogenase (G6PD) deficiency is an X-chromosomal-linked abnormality often associated with hemolytic anemia. The G6PD variants obtained from 2 unrelated males, one associated with enzyme deficiency and history of hemolytic jaundice, and the other associated with enzyme deficiency but no hemolytic problems, were examined. Although the 2 subjects have no known consanguinity, the two enzymes could not be distinguished from each other in respect to their electrophoretic mobilities and kinetic properties, both exhibiting slower than normal anodal electrophoretic mobility, lower Km for G6P and NADP and higher rate of utilization of 2-deoxy-G6P and deamino-NADP. An unique double-banded pattern was observed in starch gel electrophoresis at pH 7.0 and pH 8.6. The variant is distinguished from all reported Gd variants, and it is designated Gd(-) Santamaria.
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PMID:A glucose-6-phosphate dehydrogenase variant, Gd(-) Santamaria found in Costa Rica. 643 30

A new glucose 6-phosphate dehydrogenase (G6PD) variant associated with chronic nonspherocytic hemolytic anemia was discovered in Japan. The patient showed hemolytic crises after upper respiratory infections. The enzyme activity was about 3.8% of the normal. The partially purified enzyme revealed slow anodal electrophoretic mobility, high Km NADP, marked thermal-instability, and increased affinity for a substrate analogue (deamino-NADP). A particular characteristic of this enzyme was a biphasic pH curve with a greatly increased activity at low pH values. From these results, this variant was clearly different from hitherto observed G6PD variants, and was designated G6PD Asahikawa.
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PMID:A unique electrophoretic slow-moving glucose 6-phosphate dehydrogenase variant (G6PD Asahikawa) with a markedly acidic pH optimum. 650 May 58

A new glucose-6-phosphate dehydrogenase (G6PD) variant associated with chronic nonspherocytic hemolytic anemia was discovered. It was found in a 2-year-old male who had a hemolytic crisis after an upper respiratory tract infection. The enzyme activity of the variant was 8.4% of that of the normal enzyme. The enzymatic characteristics were slower than normal anodal electrophoretic mobility, low Km G6P, normal Km NADP, increased utilization of substrate analogues, high Ki NADPH, decreased heat stability, and an alkaline pH optimum. From these results, this was considered to be a new variant and was designated G6PD Sendagi.
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PMID:G6PD Sendagi: a new glucose-6-phosphate dehydrogenase variant associated with congenital hemolytic anemia. 665 37

A new variant of G6PD associated with chronic nonspherocytic hemolytic anemia (CNSHA) in a Japanese male is described. This variant is unique in that it has a normal electrophoretic mobility, normal Km for glucose-6-phosphate and NADP, and a normal utilization of the substrate 2-deoxyglucose-6-phosphate and deamino-NADP. It also shows a decreased thermal stability and a biphasic pH curve. These characteristics distinguish this variant from previously reported variants associated with CNSHA and we have called it G6PD Kanazawa.
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PMID:G6Pd Kanazawa: a new variant of glucose-6-phosphate dehydrogenase associated with congenital nonspherocytic hemolytic anemia. 681 68

Pentose phosphate shunt activity was studied by the release of 14CO2 from 14C-1-glucose and 14C-2-glucose in the red cells of five patients with pyruvate kinase deficiency and found to be significantly decreased after new methylene blue stimulation when compared to high reticulocyte controls. Incubated Heinz body formation was increased and the ascorbate cyanide test was positive in blood from these patients. The activity of glucose-6-phosphate dehydrogenase (G6PD) as well as that of 6-phosphogluconate dehydrogenase (6PGD) was inhibited to 20% of baseline in normal red cell haemolysate by 4 mM 2,3-diphosphoglycerate at pH 7.1. 2,3-Diphosphoglycerate was a competitive inhibitor with 6-phosphogluconate (Ki=1.05 mM) and a noncompetitive inhibitor with NADP (Ki=3.3 mM) for 6PGD. Since the intracellular concentrations of glucose-6-phosphate, 6-phosphogluconate and NADP are below their Kms for G6PD and 6PGD, the kinetic data suggest that increased concentrations of 2,3-diphosphoglycerate in pyruvate kinase deficient red cells are sufficiently high to suppress pentose phosphate shunt activity. This suppression may be an additional factor contributing to the haemolytic anaemia of pyruvate kinase deficiency, particularly during periods of infection or metabolic stress.
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PMID:Inhibition of the pentose phosphate shunt by 2,3-diphosphoglycerate in erythrocyte pyruvate kinase deficiency. 686 May 90

This paper describes a new G-6-PD variant designated Guadalajara, which was found in a Mexican boy suffering from chronic hemolytic anemia. The red cell enzyme activity of the subject is about 14%. The mutant enzyme showed rapid electrophoretic mobility, slightly increased affinity for glucose-6-phosphate, slightly decreased affinity for NADP+, moderately elevated utilization of substrate analogues, and normal heat stability, pH curve, and inhibition by NADPH. G-6-PD Guadalajara differs from all previously reported variants and is the first variant associated with chronic hemolysis found in Mexico.
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PMID:G-6-PD Guadalajara. A new mutant associated with chronic nonspherocytic hemolytic anemia. 712 46

A new glucose-6-phosphate dehydrogenase (G6PD) variant associated with chronic nonspherocytic hemolytic anemia was reported. The patient, a 6-year-old Japanese male, was noticed to have hemolytic anemia soon after birth, and a diagnosis of G6PD deficiency was made at the age of 2. He had episodes of hemolytic crisis several times after upper respiratory infection. G6PD activity of the patient was 5.5% of normal. The enzymatic characteristics were examined when he was 5 years old, and his G6PD showed faster-than-normal electrophoretic mobility, low Km G6P, high Km NADP, low Ki NADPH, normal utilization of substrate analogues, heat instability, and a normal pH optimum curve. From these results, this was considered to be a new variant and was designated G6PD Nagano. Infection-induced hemolysis and chronic hemolytic anemia seem to be due to markedly impaired enzyme activity and thermal instability.
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PMID:A new glucose-6-phosphate dehydrogenase variant (G6PD Nagano) associated with congenital hemolytic anemia. 716 14


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