Enzymatic pattern of glucose metabolic pathways in pyruvate kinase-deficient erythrocytes.

It has been shown that in some cases of congenital non-spherocytic haemolytic anaemia (CNSHA) with pyruvate kinase deficiency, the primary defect may be related to diminished magnesium-stimulated ATPase activity, followed by elevation of the erythrocyte ATP level. ATP as the end product of glycolysis inhibits by negative feedback control the activities of key glycolytic enzymes involved in energy production, i.e. pyruvate kinase (PK) and phosphofructokinase (PFK). Erythrocyte-deficient PK, however, is insensitive to the stimulating effect of fructose 1,6-diphosphate (FDP), which is normally a positive effector of PK. Both competing effectors, i.e. ATP and FDP, seem to show specific interaction. PK, inactive in the presence of high concentrations of ATP, seems to lose its sensitivity to FDP. This effect persists until ATP molecules are present in excess. In vitro incubation of deficient PK with ATPase resulted in increased PK activity as well as in recovery of its sensitivity to the stimulating effect of FDP. The same effects were obtained in vivo by administering magnesium levulinate intravenously to CNSHA patients with PK deficiency. This may indicate that magnesium ions stimulate deficient ATPase activity and lead to diminution of ATP as a negative effector for other regulatory enzymes.