Modification of phospholipid metabolism in human red cells by primaouine A possible mechanism in drug-induced hemolysis

Abstract

Primaquine stimulated the incorporation of 1- 14C-labeled long chain fatty acids into lecithin of the intact red cell but inhibited their incorporation into phosphatidylethanolamine. This differential effect of primaquine on phospholipid synthesis was shown to be controlled by the amount of the specific lysophospholipid available to the red cell. In this capacity the lysophospholipids functioned as substrates rather than as physical agents. Based on their accessibility or binding affinity to albumin, two pools of lysolecithin could be defined in the intact red cell. Removal of the accessible lysolecithin from the red cell resulted in a marked increase of osmotic fragility in the presence of primaquine. Virtual restoration of osmotic resistance could be effected by the replacement of the lysolecithin. It is proposed that a pool of lysolecithin bound to the red cell contributes to the osmotic stability of the cell and that primaquine induced hemolysis is related to a depletion of this pool consequent to an enhanced rate of conversion of lysolecithin to lecithin.