Pyrimidine 5′nucleotidase and several other red cell enzyme activities in <i>β</i>‐thalassaemia trait

Corrons, Joan‐Lluís Vives; Pujades, M. A.; Bascompte, Jordi; Jou, Josep M.; Rozmán, C; Ester, A.

doi:10.1111/j.1365-2141.1984.tb03978.x

Cited by 25 publications

(20 citation statements)

References 15 publications

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“…In thalas sémie red blood cells PK and AK activities are nor mal or higher than normal. The only enzyme which shows marked decrease is P5'N [5]. The same pattern is described in subjects with occupational lead over load [13].…”

supporting

confidence: 50%

“…Acquired defi ciency of P5' N has been described in subjects with oc cupational lead overburden and in normal red cell in vitro exposed to very low lead concentrations [2]. De creased P5'N activity has also been demonstrated in several cases of lympho-and myeloproliferative dis orders [3], in the erythroblastopenia of childhood [4] and in the p-thalassemic trait [5]. P5'N has been de scribed recently by Beutler [6] as the unique age-re lated red blood cell enzyme whose activity steadily decreases during the whole red blood cell life.…”

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confidence: 99%

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Pyrimidine 5′-Nucleotidase Acquired Deficiency in β-Thalassemia: Involvement of Enzyme-SH Groups in the Inactivation Process

David¹,

Vota²,

Piga³

et al. 1989

Acta Haematol

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Pyrimidine 5′-nucleotidase (P5′N) partial deficiency has been described in several hematological disorders and also in the β-thalassemic trait. To check if the P5’N deficiency in thalassemia was acquired we used thalassemic red cells (from either homo- or heterozygous subjects), whose P5′N activity was lower than in control cells. After separation on a density gradient, activity in lighter cells was similar to controls and less than 50% in denser cells. The most probable mechanism for this faster inactivation involves enzyme -SH groups modification by oxidation and reaction with monofunctional aldehydes produced by membrane lipid peroxidation. In vitro challenge of thiol enzymes as pyruvate kinase (PK), adenylate kinase (AK) and P5′N with increasing concentrations of GSSG, hexanal (HEX) and 4-hydroxynonenal (HNE), showed that HNE is the most powerful among the enzyme inhibitors tested and that P5′N activity is a more sensitive index of -SH groups damage, when compared to PK and AK.

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confidence: 99%

Pyrimidine 5′-Nucleotidase Acquired Deficiency in β-Thalassemia: Involvement of Enzyme-SH Groups in the Inactivation Process

David¹,

Vota²,

Piga³

et al. 1989

Acta Haematol

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“…These results allowed us to conclude that: (1) P5N was highly sensitive to the effect of RBC peroxidation, probably through the peroxide radicals involved in the production of MDA, and (2) the assay system used provided a means for measuring the sensitivity of the different RBC enzymes to an oxidative threat. In addition, our results supported the hypothesis of a probable in vivo oxidative stress mechanism as the cause of the acquired P5N deficiency observed in P-thalassaemia trait [3]. Although the evidence presented by David et al [1] strongly confirms our results, no mention has been made of our paper, published in Enzyme one year ago [2], In our opinion, the results of David et al [1] stress the fact that P5N-SH groups are more sensi tive to 4-hydroxynonenal than to other aldehydes, but neither the importance of these compounds in p-thal assaemia nor their possible in vivo effect on P5N activity has been elucidated.…”

supporting

confidence: 76%

Pyrimidine 5′-Nucleotidase Acquired Deficiency in Beta-Thalassaemia: Involvement of Enzyme-SH Groups in the Inactivation Process

Jl¹,

Ma²,

Colomer³

1990

Acta Haematol

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“…Previous studies were made difficult by the acquired deficiency of P5ЈN-1 associated with ␤ thalassemia trait. 19,30 It is also possible that genetic analysis will identify atypical forms of P5ЈN-1 deficiency that may not produce the classical phenotype but could explain some of the many cases of inherited hemolysis with no identifiable cause. 5 Database searches show expression of P5ЈN-1 cDNA in various tumors (lung, ovary, colon, bladder), fetal tissues (lung, heart, spleen, liver), adult testis, and brain.…”

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Genetic basis of hemolytic anemia caused by pyrimidine 5′ nucleotidase deficiency

Marinaki

Escuredo

Duley

et al. 2001

Blood

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Pyrimidine 5 nucleotidase (P5N-1) deficiency is an autosomal recessive condition causing hemolytic anemia characterized by marked basophilic stippling and the accumulation of high concentrations of pyrimidine nucleotides within the erythrocyte. It is implicated in the anemia of lead poisoning and is possibly associated with learning difficulties. Recently, a protein with P5N-1 activity was analyzed and a provisional complementary DNA (cDNA) sequence published. This sequence was used to study 3 families with P5N-1 deficiency. This approach generated a genomic DNA sequence that was used to search GenBank and identify the gene for P5N-1. It is found on chromosome 7, consists of 10 exons with alternative splicing of exon 2, and produces proteins 286 and 297 amino acids long. Three homozygous mutations were identified in this gene in 4 subjects with P5N-1 deficiency: codon 98 GAT3GTT, Asp3Val (linked to a silent polymorphism codon 92, TAC3TAT), codon 177, CAA3TAA, Gln3termination, and IVS9-1, G3T. The latter mutation results in the loss of exon 9 (201 bp) from the cDNA. None of these mutations was found in 100 normal controls. The DNA analysis was complicated by P5N-1 pseudogenes found on chromosomes 4 and 7. This study is the first description of the structure and location of the P5N-1 gene, and 3 mutations have been identified in affected patients from separate kindreds. ( IntroductionPyrimidine 5Ј nucleotidase (P5ЈN-1, also known as uridine-5Ј-monophosphate hydrolase-1) catalyzes the dephosphorylation of the pyrimidine 5Ј monophosphates UMP and CMP to the corresponding nucleosides. A deficiency of this enzymatic activity was first identified by Valentine et al 1,2 in erythrocyte stroma while investigating patients with hemolytic anemia characterized by marked basophilic stippling. Initial studies showed very high concentrations of what were assumed to be adenine nucleotides in the erythrocytes, but these were later found to be pyrimidine nucleotides; the red blood cells (RBCs) also contained high levels of glutathione and reduced activity of ribose-phosphate pyrophosphokinase. Studies on 3 additional kindreds with hemolytic anemia and basophilic stippling demonstrated absent or markedly reduced pyrimidine 5Ј nucleotidase activity in their RBCs. 3 Reports of 40 patients with this condition have been published, with presumably large numbers undetected. However, because of the lack of a simple and reliable test for carriers, the exact prevalence of the condition is unknown. Reported numbers of homozygotes suggest that it is the third most common RBC enzymopathy-after glucose-6-phosphate dehydrogenase and pyruvate kinase deficiency-causing hemolysis. 4 Although the first 6 patients reported were all female, a number of affected males have been reported since then, and the pattern of inheritance is typical of an autosomal recessive disorder. 5 Additional studies have suggested that there are 2 isozymes of P5ЈN in RBCs, one with a preference for UMP and CMP, referred to as P5ЈN-1, and one able to hydrolyze deoxypyrimid...

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Pyrimidine 5′nucleotidase and several other red cell enzyme activities in β‐thalassaemia trait

Cited by 25 publications

References 15 publications

Pyrimidine 5′-Nucleotidase Acquired Deficiency in β-Thalassemia: Involvement of Enzyme-SH Groups in the Inactivation Process

Pyrimidine 5′-Nucleotidase Acquired Deficiency in β-Thalassemia: Involvement of Enzyme-SH Groups in the Inactivation Process

Pyrimidine 5′-Nucleotidase Acquired Deficiency in Beta-Thalassaemia: Involvement of Enzyme-SH Groups in the Inactivation Process

Genetic basis of hemolytic anemia caused by pyrimidine 5′ nucleotidase deficiency

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