Biosynthesis of dolichol and cholesterol during embryonic development of the chicken

Abstract

The polyisoprenol dolichol, in its phosphorylated form, serves as the lipid intermediate in N-linked glycoprotein synthesis, and shares a portion of its biosynthetic pathway with cholesterol. The synthesis of dolichol and cholesterol was followed over the course of development by incubating chicken embryos with [ 3H]acetate for 24-h intervals. Dolichol and cholesterol were isolated from the non-saponifiable lipids and identified by gel filtration and thin-layer chromatography. It was found that the rate of acetate incorporation into these two compounds per g of embryo decreased from days 8 to 14 of development. In the whole embryo, over the course of development the ratio of the rates of acetate incorporation into dolichol to that into cholesterol decreased markedly. These results suggest that mechanisms exist for controlling the differential rates of dolichol and cholesterol synthesis during development. When labeled organs from day 10 embryos were analyzed, it was found that the ratio of the rates of synthesis of dolichol to cholesterol in brain was about 14-fold lower than that in liver and heart. Similar values for the rates of synthesis of these two compounds were obtained when isolated organs were labeled in vitro. These data suggest that these three organs are capable of synthesizing dolichol and cholesterol de novo, and that each organ independently regulates the rates of synthesis of dolichol and cholesterol.