Effect of liposomes on substrate uptake by isolated guinea-pig liver mitochondrial and microsomal membranes.

Abstract

The effect of adding small unilamellar lecithin liposomes, prepared in the presence of cytidine-diphosphoryl-1,2-diglycerides (CDP-diglycerides) or cytochrome c, on microsomal biosynthesis of phosphatidylinositol and NADPH-cytochrome c reduction and on mitochondrial biosynthesis of polyglycerophosphatides and succinate-cytochrome c reduction was studied in isolated guinea-pig liver subcellular membranes. Both microsomal biosynthesis of phosphatidylinositol and mitochondrial biosynthesis of phosphatidylglycerol were significantly reduced when CDP-diglycerides associated with liposomes were used, suggesting that some CDP-diglycerides were entrapped by liposomal membranes and were not available to subcellular membranes as substrates. The degree of decrease in phospholipid biosynthesis depended on the membrane and the nature of fatty acids in CDP-diglycerides. The composition of mitochondrial polyglycerophosphatides synthesized in the presence of CDP-diglycerides-liposomes was also affected in respect to the amount of phosphatidylglycerol formed. The reduction of cytochrome c in both microsomal and mitochondrial membranes was also decreased when liposomes were present in the assay system, but to a lesser degree than the phospholipid biosynthesis. These results indicate that the cytochrome c liposome association did not provide efficient protection of this substrate from the subcellular reduction. When chlorpromazine was also present with liposomes in the assay system, the NADPH-cytochrome c reduction in microsomes was scarcely affected, while the succinate-cytochrome c reduction in mitochondria was dependent on the concentration of chlorpromazine and could be completely abolished. These results were interpreted in terms of liposomal interaction with substrates in competition with subcellular membranes for the same substrates.