Formation of glycerol from glucose in rat brain and cultured brain cells. Augmentation with kainate or ischemia

An increase in the concentration of glycerol in the ischemic brain is assumed to reflect degradation of phospholipids of plasma membranes. However, glycerol could, theoretically, be formed from glucose, which after glycolytic conversion to dihydroxyacetone phosphate, could be converted to glycerol-3-phosphate and hence to glycerol. We show here that C-13-labeled glycerol accumulate in incubation media of cultured cerebellar granule cells and astrocytes incubated with [C-13]glucose, 3 mmol/L, demonstrating the formation of glycerol from glucose. Co-incubation of cerebellar granule cells with kainate, 50 mu mol/L, led to increased glucose metabolism and increased accumulation of [C-13]glycerol. Accumulation of [C-13]glycerol and its precursor, [C-13]glycerol-3-phosphate, was evident in brain, but not in serum, of kainate-treated rats that received [U-C-13]glucose, 5 mu mol/g bodyweight, intravenously and survived for 5 min. Global ischemia induced by decapitation also caused accumulation of [C-13]glycerol and [C-13]glycerol-3-phosphate. These results show that glycerol can be formed from glucose in brain; they also demonstrate the existence of a cerebral glycerol-3-phosphatase activity. Ischemia-induced increases in brain glycerol may, in part, reflect an altered metabolism of glucose, in which glycerol formation, like lactate formation, acts as a redox sink.