The use of newly synthesized phospholipids for assembly into secreted hepatic lipoproteins

We have recently shown (Vance, J.E. (1988) Biochim. Biophys. Acta 963, 70-81) that the percent distribution of molecular species of phosphatidylcholine (PC) derived from [methyl-3H]choline and [3-3H]serine, and phosphatidylethanolamine (PE) derived from [3-3H]serine were different in secreted lipoproteins and in the cultured hepatocytes from which the lipoproteins were produced. The species 1-stearoyl-2-arachidonoyl PC and PE were selectively not secreted. How this selection occurs is not known. One possible explanation is that secreted phospholipids are representative of the newly synthesized pool, whereas the molecular species composition of bulk cellular phospholipids has been altered by selective deacylation or by deacylation-reacylation. This hypothesis has been tested. The percent distribution of radioactivity from [1-3H]ethanolamine, [3-3H]serine and [methyl-3H]choline in nascent cellular and secreted PE and PC molecular species was examined by high-performance liquid chromatography. From [3H]serine labeling, the percent distribution of [3H]PE species in the medium after 4 h resembled closely that in cells 0.5 h, but not 4 h, after labeling. Thus, nascent phosphatidylserine-derived PE was immediately earmarked for secretion before remodeling occurred. Similarly, newly made rather than 'old' PE and PC from alternative biosynthetic sources may be preferred for assembly into lipoproteins. In addition, PE methyltransferase apparently preferred newly made, rather than remodelled, serine-derived PE for methylation to PC. In no instance (i.e., neither for any phospholipid nor any precursor) was there evidence that 'old' rather than 'new' phospholipid was specifically selected for secretion.