Utilization of Alpha-Ketoglutarate by Red Blood Cells for Glutathione Synthesis

Abstract

INVESTIGATIONS in this laboratory have indicated that glutamic-oxaloacetic transaminase activity is increased in young red blood cells. Subsequent ageing is associated with a marked decrease in activity^1–3. In an attempt to provide some understanding of the possible physiological role of this enzyme in red cells, we were led to an examination of the metabolism of glutathione. Sufficient information has already become available to indicate that erythrocytes possess the enzymatic machinery for synthesizing glutathione^4–6. The relatively rapid half-turnover time of glutathione, 65 and 96 h respectively in rat and human red cells^4,7, suggests that this mechanism plays some part in their metabolic economy. In addition, it indicates that adequate supplies of substrate amino-acids are available to the erythrocyte. In view of the relative impermeability of red cells to glutamic acid⁸ there is some doubt as to the exact mechanism by which supplies of this amino-acid are made available to the red cell under physiological conditions. Consideration was therefore given to the possibility that glutamic acid might be supplied through transamination of another metabolic intermediate after its entry into the erythrocyte. This communication gives data indicating that α-ketoglutarate, the most obvious possibility, can be incorporated into glutathione in vitro by human red cells.