The in vivo ageing of red cell enzymes: direct evidence of biphasic decay from polycythaemic rabbits with reticulocytosis.

Abstract

The rate at which the activities of red cell enzymes decay during maturation of the reticulocyte and ageing of the erythrocyte is poorly understood. It has recently been suggested that loss of enzyme activity may be rapid during reticulocyte maturation and occur slowly thereafter. We have now devised a rabbit model in which reticulocytosis is combined with transfusional polycythaemia. This makes it possible to follow the enzymatic activity of a cohort of reticulocytes without the interfering effect of newly formed cells. In this model the reticulocyte count of the experimental animals falls from about 60% to subnormal levels within 4 d. Red cell hexokinase activity declined rapidly with more than half of the activity being lost within 7 d, little change occurring thereafter. Glucose-6-phosphate dehydrogenase activity declined more gradually, but also followed a biphasic course. The fall of pyrimidine 5' nucleotidase activity was the slowest of the three age-dependent enzymes studied. This is consistent with our observations in children with transient erythroblastopenia of childhood, in which this enzyme, alone of the age-dependent enzymes, was found to be decreased in a senescent red cell population. In contrast to the three age-dependent enzymes studied, the activity of lactate dehydrogenase remained unchanged during the course of the experiment. These studies provide direct verification of the suggestion that the decline of red cell enzyme activities may be biphasic. They show, moreover, that enzyme decay is not only rapid in reticulocytes, but also in young erythrocytes.