Apolipoproteins of the orotic acid fatty liver: implications for the biogenesis of plasma lipoproteins.

Abstract

Rats fed orotic acid develop fatty livers characterized by triglyceride-laden, membrane-bounded vesicles designated ''liposomes.'' We have measured the levels of apolipoproteins in isolated liposomes and other subcellular fractions by SDS-polyacrylamide gel electrophoresis, electrotransfer, and immunodecoration. Apolipoproteins Bh, Bl, E, and C appear to cofractionate; for these proteins, the liposomal pool represents a large portion of their total intracellular mass. However, liposomes are deficient in both variants of apoB relative to apoE and apoC when compared with rat plasma very low density lipoprotein (VLDL). Albumin and apolipoproteins A-I and A-IV are also found in liposomes, but this organelle represents a minor fraction of their total intracellular mass. The liposomal apolipoproteins show varying degrees of association with cisternal lipid and with organelle membranes. Orotic acid may selectively block VLDL production at the level of particle assembly or transorganellar movement. We conclude that liposomal contents probably represent exaggerated accumulations of VLDL assembly intermediates, and that the intracellular partitioning of high density lipoprotein-destined from VLDL-destined components occurs at an early stage in particle biogenesis. Moreover, some unique structural feature of apoB may effect movement of VLDL assembly intermediates through secretory organelles.