Primaquine-mediated oxidative metabolism in the human red cell. Lack of dependence on oxyhemoglobin, H2O2 formation, or glutathione turnover.

Stimulation of the hexose monophosphate shunt by primaquine results from the oxidation of NADPH by primaquine. This conclusion was based on the observations that primaquine lowered cellular NADPH but not GSH and that, in red cells in which the GSH was unavailable for reaction, primaquine still stimulated the rate of the hexose monophosphate shunt. In a non-cellular system, primaquine interacted with NADPH, but not GSH, to produce H2O2. Stimulation of the hexose monophosphate shunt by primaquine does not primarily involve H2O2 accumulation since stimulation of the pathway by primaquine was also observed in red cells containing methemoglobin, a red cell preparation in which no H2O2 accumulates. Methemoglobin prevented the formation and/or accumulation of H2O2 in intact red cells incubated with primaquine as well as in a non-cellular system containing primaquine plus Fe2+-EDTA as an H2O2 source. Methemoglobin probably acts by scavenging reactive intermediates since oxyhemoglobin was formed from methemoglobin in the non-cellular experiments. In the red cell, primaquine stimulated glucose-dependent conversion of methemoglobin to oxyhemoglobin.