抄録
Phosphofructokinase (PFK) defect has been demonstrated in erythrocyte as well as in muscle of patients with glycogenosis VII, which is characterized by a genetic defect of muscle type PFK. Pathogenesis of the shortened life span of the erythrocytes was studied by the determination of behaviors in glycolytic intermediates and nucleotides, glycolytic capacity and kinetic properties of PFK of the affected erythrocytes. Enzymatic analyses showed a 80% increase of fructose-6-phosphate and a 60% decrease of fructose-1, 6-diphosphate with a decline of triose phosphates and monoglyceric acids, being attributed to a block at the site of PFK in the glycolytic pathway. 2, 3-Diphosphoglyceric acid in the erythrocytes was decreased to 50% which resulted in the increased affinity of the hemoglobin for oxygen. The ATP content was slightly decreased with a three to four fold increase of AMP and ADP. The low rate of glycolysis in the erythrocytes was demonstrated in vitro by the reduced production of lactate from glucose. The pH dependency of the lactate production was observed in control and affected erythrocytes, and lactate production was 25%, 37% and 38% of normal at pH 6.7, 7.4 and 8.0, respectively. Concomitant mesurement of fructose-1, 6- diphosphate and glucose-6-phosphate in the erythrocytes revealed that the ratio of fructose-1, 6-diphosphate to glucose-6-phosphate was closely related to the rate of glycolysis, suggesting the significant contribution of residual PFK to the control of the glycolysis even in the affected erythrocytes. PFK in the deficient erythrocytes differed from normal in its kinetic properties: altered pH dependency and increased affinity for ATP. It may be concluded that the diminished life span of the PFK deficient erythrocytes is caused by the impairment of glycolysis due to the block at the site of PFK. Furthermore not only the low activity but also the kinetic aberration of the residual PFK might accout for the matabolic block in the affected erythrocytes.
