Mechanisms for the effects of ethanol on hepatic phosphatidate phosphohydrolase

Abstract

The effects of the i.m. administration of glycerol and dihydroxyacetone (40 mmol/kg body wt), sorbitol and glucose (20 mmol/kg body wt) or NaCl (1.5 mmol/kg body wt in 10 ml of water/kg body wt) were investigated on soluble phosphatidate phosphohydrolase (EC 3.1.3.4) and certain metabolites in rat liver. The effects of ethanol and glycerol on phosphatidate phosphohydrolase were also studied in isolated perfused livers. The administration of glycerol, sorbitol and dihydroxyacetone in vivo increased hepatic phosphatidate phosphohydrolase activity by 137, 63 and 32%, respectively in 4 h. A significant positive correlation was found between the hepatic sn-glycerol 3-phosphate concentration and phosphatidate phosphohydrolase after the administration of various substrates in vivo. The soluble phosphatidate phosphohydrolase activity tended to increase during perfusions of isolated rat livers without added substrates, and neither ethanol nor glycerol produced additional effects. The activity of soluble phosphatidate phosphohydrolase was 2.5 .times. higher in the livers of hyperthyroid rats than in normal rats. This activity was not influenced by intragastric ethanol or glycerol administration, nor was the concentration of sn-glycerol 3-phosphate changed by these compounds. The ethanol-induced increase in hepatic phosphatidate phosphohydrolase may at least in part be mediated by the hepatic concentration of metabolites, probably by the concentration of sn-glycerol 3-phosphate.