Hormonal Control of Apolipoprotein Synthesis

BIOCHEMICAL STUDIES The simplest and most thoroughly studied model of apolipoprotein synthesis to date comes from an avian apoprotein. ApoVLDL-II is a major apolipoprotein in VLDL of the laying hen (13). It is an 82-amino acid peptide, the sequence of which is shown in Figure 1 (14, 15, 20). It exists in blood as a dimer, the two monomers being connected by a disulfide bond at residue 75. Under the influence of estrogen, apoVLDL-II becomes a very major protein synthesized by the liver (see below). The protein is thus relatively easy to isolate in large quantities, and antisera can be readily generated against it. These facts aided tremendously in the initial studies on the biosynthesis of apoVLDL-II. When apoVLDL-II is translated in vitro (from either total liver mRNA or from liver polysomal RNA), the initial translation product has an appar­ ent molecular weight of approximately 11,000 whereas that of apo VLDL-II is approximately 9,500 (13). Further analysis of the product (10, 12, 13, 16), together with subsequent data from DNA sequencing (see below), indicates that the initial product has an N-terminal peptide extension of 24 amino acids. The sequence of this signal peptide is shown in Figure 1 (10, 16). The main features in this sequence are very similar to those reported by others