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Inhibition of the pentose phosphate shunt by 2,3‐diphosphoglycerate in erythrocyte pyruvate kinase deficiency
Author(s) -
Tomoda Akio,
Lachant Neil A.,
Noble Nancy A.,
Tanaka Kouichi R.
Publication year - 1983
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.1365-2141.1983.tb02122.x
Subject(s) - pentose phosphate pathway , pyruvate kinase , dehydrogenase , chemistry , pyruvate kinase deficiency , biochemistry , diphosphoglycerate , endocrinology , enzyme , medicine , glycolysis , biology , hemoglobin
S ummary . Pentose phosphate shunt activity was studied by the release of 14 CO 2 from 14 C‐1‐glucose and 14 C‐2‐glucose in the red cells of five patients with pyruvate kinase deficiency and found to be significantly decreased after new methylene blue stimulation when compared to high reticulocyte controls. Incubated Heinz body formation was increased and the ascorbate cyanide test was positive in blood from these patients. The activity of glucose‐6‐phosphate dehydrogenase (G6PD) as well as that of 6‐phosphogluconate dehydrogenase (6PGD) was inhibited to 20% of baseline in normal red cell haemolysate by 4 mM 2,3‐diphosphoglycerate at pH 7·1. 2,3‐Diphosphoglycerate was a competitive inhibitor with 6‐phosphogluconate ( K i = 1·05 mM) and a noncompetitive inhibitor with NADP ( K i = 3·3 mM) for 6PGD. Since the intracellular concentrations of glucose‐6‐phosphate, 6‐phosphogluconate and NADP are below their K m s for G6PD and 6PGD, the kinetic data suggest that increased concentrations of 2,3‐diphosphoglycerate in pyruvate kinase deficient red cells are sufficiently high to suppress pentose phosphate shunt activity. This suppression may be an additional factor contributing to the haemolytic anaemia of pyruvate kinase deficiency, particularly during periods of infection or metabolic stress.