Inhibition of hexose monophosphate shunt in young erythrocytes by pyrimidine nucleotides in hereditary pyrimidine 5‘ nucleotidase deficiency

Abstract

Recent reports have suggested that haemolytic anaemia in pyrimidine 5′ nucleotidase (P5′N) deficiency might be due to impaired erythrocyte hexose monophosphate shunt (HMS). To investigate the relationship between pyrimidine accumulation, HMS impairment and shortened red‐cell survival, we tested glucose 6‐phosphate deydrogenase (G‐6PD), HMS, P5′N activities and the UV spectrum in whole red cells and in red cells of different age from 2 P5′N‐deficient patients with different degrees of haemolytic anaemia. In whole red cells we found a reduction of both GdPD and stimulated HMS activity in the presence of a variable amount of pyrimidine nucleotides (37.79 and 17.88 pmol/gHb respectively). A drastic inhibition of stimulated HMS activity was already present in the lightest red‐cell fractions from patient 1, who presented a more severe haemolytic anaemia. The variable degree of pyrimidines found among red cell fractions, with a minor accumulation in the older red cells, supports the hypothesis that pyrimidine accumulation and HMS impairment occur in the younger erythrocytes of P5′N‐deficient patients.

Proteomics reveals reduced expression of transketolase in pyrimidine 5′‐nucleotidase deficient patients

“…Reticulocytes exhibit very high P5N activity that declines rapidly in young RBCs, while matured RBCs show very low P5N activity . Mutations in the NT5C3A gene can result in the subsequent accumulation of pyrimidine nucleotides in the RBC, which has been previously described to adversely affect key metabolic pathways .…”