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Red cell metabolism in hereditary pyrimidine 5′‐nucleotidase deficiency: effect of magnesium
Author(s) -
Lachant Neil A.,
Tanaka Kouichi R.
Publication year - 1986
Publication title -
british journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.907
H-Index - 186
eISSN - 1365-2141
pISSN - 0007-1048
DOI - 10.1111/j.1365-2141.1986.tb07545.x
Subject(s) - magnesium , chemistry , red cell , biochemistry , enzyme , hexokinase , metabolism , nucleotidase , cytidine , 5' nucleotidase , endocrinology , medicine , glycolysis , biology , organic chemistry
S ummary Since pyrimidine nucleotides avidly bind magnesium, we tested the hypothesis that the haemolytic anaemia in hereditary pyrimidine 5′‐nucleoti∼ dase (P5N) deficiency is due to a state of functional magnesium depletion in the red cell (RBC). In haemolysates from normal subjects, cytidine triphos‐phate (CTP) inhibited the activity of pyruvate kinase in a competitive manner for magnesium. The CTP K i was 0.4 mmol/1. CTP inhibited the activity of hexokinase in a competitive manner for ATP (Mg‐ATP 2‐ ) with a K i of 4 mmol/1. The inhibitory effect of CTP on both enzymes was overcome by increasing the magnesium content of the test system. Since CTP appeared to inhibit enzymes which required magnesium as a cofactor or Mg‐ATP 2‐ as a substrate, we tested the effect of exogenous magnesium on the metabolism of P5N deficient RBC. The autohaemolysis test, the incubated Heinz body assay and the rate of glucose oxidation by the pentose phosphate shunt were abnormal in the intact RBC from a patient with hereditary P5N deficiency. The addition of MgCl 2 (6–10 mmol/1) did not improve these abnormal in vitro measures of metabolism in the P5N deficient RBC. This lack of effect of exogenous magnesium may be due to the slow uptake of magnesium by the human RBC.