B-14. 先天性及び後天性赤血球ホスホフルクトキナーゼ活性低下症

抄録

The control mechanism of glycolysis in human erythrocytes was analysed placing an emphasis upon the relationship between phosphofructokinase (PFK) activity and 2, 3-bisphosphoglycerate (2, 3-DPG) level. The blood sample was directly taken into a syringe containing the perchloric acid in order to minimize the changes in metabolite levels after venopuncture. Alterations in glycolysis in erythrocytes in the patients with hereditary eythrocyte PFK deficiency (PFK activity was 30% of normal control), diabetic ketoacidosis and chronic renal failure in acidosis were investigated by the enzymatic analysis of glycolytic intermediates and adenine nucleotides. The following results were obtained.
1) In PFK deficiency, the levels of glucose-6-phosphate (G6P) and fructose-6-phosphate (F6P) were increased, while those of fructose-1, 6-bisphosphate (FDP), dihydroxyacetone phosphate (DHAP) plus glyceraldehyde-3-phosphate (GAP) and 2, 3-DPG were decreased.
2) In diabetic ketoacidosis, the level of F6P was significantly higher than normal control and levels of FDP, DHAP plus GAP, 2, 3-DPG and 3-phosphoglycerate were significantly lowered. In chronic renal failure, the similar patterns in the levels of glycolytic intermediates were demonstrated when the levels were compared with those of the non-azotemic patients with comparable anemia and reticulocytosis.
These findings indicate that glycolysis in erythrocytes in these genetic and aquired diseases is inhibited at PFK step. It was demonstrated in experiments using human erythrocyte suspension and purified PFK preparations that the inhibition in acidosis was mainly due to the increased hydrogen ion concentration. Thus, a reduction in erythrocyte PFK activity is caused not only by the hereditary defect of enzyme protein but also by the elevated concentration of hydrogen ion in blood. The marked fall in 2, 3-DPG level is caused by the reduction of PFK activity in erythrocytes, indicating an important role of this enzyme in the regulation of the 2, 3-DPG level.