Red blood cell oxidative metabolism induced by hydroxypyruvaldehyde

Hydroxypyruvaldehyde is a substrate for the red cell glyoxalase system. It was metabolized by glyoxalase I with reduced glutathione to S-glyceroyl glutathione which was subsequently enzymatically hydrolyzed to reduced glutathione and glycerate by glyoxalase II. There was a competing spontaneous reaction of hydroxypyruvaldehyde with oxygen, which produced hydrogen peroxide, inducing oxidative metabolism in hydroxypyruvaldehyde-treated red cells. The incubation of red cells with hydroxypyruvaldehyde produced a stimulation in the flux of glucose oxidized through the hexose monophosphate shunt pathway, a stimulation in lactate production with a decrease in pyruvate production in the Embden-Meyerhoff pathway, an oxidation of reduced pyridine nucleotides and reduced glutathione to their oxidized cogeners, and changes in the oxidative status of hemoglobin. Overall, the majority of hydroxypyruvaldehyde consumption in red cell suspensions appeared to occur via non-oxidative routes, e.g. glyoxalase and/or 2-ketoaldehyde dehydrogenase, and non-enzymic protein binding. Although the observed oxidative metabolism induced by hydroxypyruvaldehyde in red cells was not severe (reduced glutathione levels in hydroxypyruvaldehyde-treated red cells were ca. 80% of the control values in untreated cells), the oxidative effects may be important in red cell ageing processes.