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Red Cell Glycolysis in a Case of 3‐Phosphoglycerate Kinase Deficiency
Author(s) -
Arese P.,
Bosia A.,
Gallo E.,
Mazza U.,
Pescarmona G. P.
Publication year - 1973
Publication title -
european journal of clinical investigation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.164
H-Index - 107
eISSN - 1365-2362
pISSN - 0014-2972
DOI - 10.1111/j.1365-2362.1973.tb00333.x
Subject(s) - phosphoglycerate kinase , pyruvate kinase , glycolysis , lactate dehydrogenase , hexokinase , glyceraldehyde , phosphofructokinase , biochemistry , dehydrogenase , red cell , population , pyruvate dehydrogenase kinase , biology , chemistry , enzyme , pyruvate dehydrogenase complex , medicine , environmental health
. A severe deficiency in red cell 3‐phosphoglycerate kinase was observed in a 62‐year‐old woman with haemolytic anaemia. Compared with a normal “young” red cell population with the same degree of reticulocytosis (6–7%) the 3‐phosphoglycerate kinase activity was reduced to 27%. A concomitant decrease of hexokinase and pyruvate kinase (both reduced by about 30%) was observed. The activities of glucoses‐phosphate dehydrogenase, phosphofructokinase, fructose‐1,6‐di‐phosphate aldolase, gIyceraIdehyde‐3‐phosphate dehydrogenase and lactate dehydrogenase were slightly increased (7 to 15%). The total glycolytic output of the deficient cells was decreased by 28% at pH 7.0, by 36% at pH 7.4 and by 34% at pH 7.6. Compared with a normal “adult” red cell population the 3‐phosphoglycerate kinase activity was reduced to 42% of the control values. Hexokinase, glyceraldehyde‐3‐phosphate dehydrogenase and lactate dehydrogenase activities were increased by approximately 20–50%. Phosphofructokinase activity was unchanged and pyruvate kinase only slightly increased. The steady state levels of the intermediates preceding the 3‐phosphoglycerate kinase step were increased 2–3 fold. The subsequent metabolites were decreased or practically unmodified. ATP, ADP, NAD+, and NADH were not affected. The reduced glutathione level was increased and the ratio of reduced to oxidized glutathione was doubled. The glycolytic output and its pH‐dependency were normal. The metabolic significance of the enzyme defect was assessed by the in vitro creation of cell stressing conditions, i.e. low pH and high pyruvate levels. In both cases, the 3‐phosphoglycerate kinase activity became limiting at low pH, glucose‐6‐phosphate accumulated at a faster rate and fructose‐ 1,6‐diphosphate and dihydroxyacetone phosphate disappeared more slowly in the deficient cells. After pyruvate loading these cells showed: a faster, more pronounced rise in 1,3‐diphosphoglycerate and a decrease in 2,3‐diphosphoglycerate (slightly increased in the controls): a drop in reduced glutathione (constant in the controls): constant ATP and slightly increased 3‐phosphoglycerate concentrations (both strongly increased in the controls): a slight increase in NADH (dropped to nil in the controls). Steady state glycolysis under normal conditions seemed to be affected by the enzyme deficiency. 3‐phosphoglycerate kinase however, became more severely limiting a low pH or after the addition of pyruvate. In these conditions, the flow was diverted to the 2,3‐diphosphoglycerate bypass, less ATP was produced and the concentration of reduced glutathione decreased. This may be assumed to have led to impairment of the ionic pump and may thus explain the increased haemolysis.