INHIBITION OF THE PENTOSE-PHOSPHATE SHUNT BY LEAD - A POTENTIAL MECHANISM FOR HEMOLYSIS IN LEAD-POISONING

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  • 1 January 1984
    • journal article
    • research article
    • Vol. 63  (3) , 518-524
Abstract
Recent investigations have disclosed a decrease in pentose phosphate shunt activity in hereditary pyrimidine 5''-nucleotidase deficiency. Clinical Pb poisoning is associated with an acquired decrease in pyrimidine 5''-nucleotidase activity. Investigations were undertaken to determine if pentose shunt activity was decreased in erythrocytes exposed to Pb, and to compare the mechanism of inhibition to that seen in hereditary pyrimidine 5''-nucleotidase deficiency. Normal erythrocytes incubated with Pb acetate in vitro demonstrated increased Heinz body formation, decreased reduced glutathione, a positive ascorbate cyanide test and a reversible suppression of pentose shunt activity in the intact erythrocyte. Pb acetate added to normal red cell hemolysates markedly inhibited the activities of glucose-6-phosphate dehydrogenase (G6PD) and phosphofructokinase. The mean Ki of Pb for G-6-P and NADP for G6PD were 1.5 and 2.1 .mu.M, respectively, which is within the range of intraerythrocytic Pb concentrations found in clinical Pb poisoning. Mg enhanced the ability of lead to inhibit G6PD. The shortened erythrocyte survival in Pb poisoning appears to be due, in part, to increased oxidant sensitivity secondary to inhibition of G6PD and the pentose shunt. The mechanism of shunt inhibition is, in part, similar to that seen in hereditary pyrimidine 5''-nucleotidase deficiency.