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)

Pyrimidine 5' nucleotidase (P5'N) acquired deficiency has been found in several hematologic disorders including beta-thalassemia. Our previous studies suggested that the aldehydes produced during membrane lipid peroxidation could play a role in P5'N inactivation in thalassemia. To evaluate the effects of the thalassemic "environment" on transfused red blood cells, we tested P5'N, pyruvate kinase (PK), glucose 6-phosphate dehydrogenase (G-6PD) activity, creatine content, reduced glutathione (GSH) levels and the hexose monophosphate shunt (HMS) in the red cells of homozygous transfusion-dependent thalassemic children, immediately following and again one month after transfusion. In red cells aged in thalassemic plasma, P5'N activity, creatine level, GSH stability and stimulated HMS flux were significantly decreased. These results fit in with the presence in thalassemic plasma of molecules interfering with antioxidant red cell defenses. Normal red cells incubated in thalassemic plasma display a significant stimulation of the basal HMS (p less than 0.01). Transfused red cell metabolic alterations could be explained by the plasma pro-oxidant activity and may contribute to reducing red cell survival in the host plasma.
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PMID:Pyrimidine 5'-nucleotidase and oxidative damage in red blood cells transfused to beta-thalassemic children. 227 76

A Bangladeshi family is described in which the genes for both hemoglobin E (Hb E) and pyrimidine 5' nucleotidase deficiency are segregating. An individual homozygous for both these conditions has a severe hemolytic anemia, whereas family members who are homozygous for Hb E are asymptomatic and those homozygous for pyrimidine 5' nucleotidase deficiency have the mild hemolytic anemia that is characteristic of this disorder. Globin-chain synthesis experiments have shown that the mechanism underlying the interaction between these two genotypes is a marked decrease in the stability of Hb E in pyrimidine 5' nucleotidase-deficient red blood cells (RBCs). It has also been found that in the enzyme-deficient RBCs in which Hb E is highly unstable, free alpha-chains, though not beta E-chains, acoumulate on the membrane. In view of the increasing evidence that the hemolysis associated with pyrimidine 5' nucleotidase deficiency results not only from an increase in the level of erythrocyte pyrimidines, but also from inhibition of the hexose monophosphate shunt activity in young erythrocytes, it is likely that the marked instability of Hb E in the enzyme-deficient cells results from oxidant damage acting on a mildly unstable Hb variant. These observations may have important implications for the better understanding of the pathophysiology of Hb E/beta-thalassemia, globally the commonest important form of thalassemia.
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PMID:Interaction of hemoglobin E and pyrimidine 5' nucleotidase deficiency. 926 98