Generation and Remodeling of Phospholipid Molecular Species in Rat Hepatocytes

In order to assess the relationship between de novo phospholipid synthesis and remodeling by deacylation-reacylation, we have pulse-labeled glycerolipids by incubating rat hepatocytes in media containing either [U-14C]glycerol or (H218O. Further incubation for up to 2 h in the absence of the labeled substrates and analysis of phosphatidylcholine (PC) and phosphatidylethanolamine (PE) provided information on the remodeling of newly synthesized molecular species by deacylation-reacylation at the sn-1 or sn-2 positions of glycerol. We conclude that de novo synthesis of PC and PE yields primarily four molecular species: 16:0-18:2 (n-6), 16:0-18:1, 16:0-22:6 (n-3), and 18:1-18:2 (n-6). Remodeling occurs in both lipid classes by replacement of the fatty acids at the sn-1 position with stearic acid, 18:0, or at the sn-2 position with arachidonic acid, 20:4 (n-6). A major molecular species of both PC and PE, 18:0-20:4 (n-6), appears to be produced by deacylation-reacylation at both the sn-1 and sn-2 positions and not to be further remodeled. De novo synthesis and remodeling of PC and PE in rat hepatocytes occur at similar rates, involve precursor-product relationships among newly synthesized molecular species, and therefore may be regulated as a single metabolic process.