Intra- and extracellular modifications of apolipoproteins.
This chapter outlined the methods used to study intra- and extracellular modifications of apolipoproteins. These and other related studies have shown that several of the apolipoproteins undergo a series of intra- and extracellular modifications as follows: All apolipoproteins studied contain an 18-26 long signal peptide which is cleaved cotranslationally by the signal peptidase of the rough endoplasmic reticulum. ApoE is further modified intracellularly with carbohydrate chains containing sialic acid and is secreted in the modified form designated apoEs. The modified apoE is subsequently desialated in plasma. ApoA-I is secreted in a proapoA-I form, which consists of 249 amino acids. The N-terminal hexapeptide of proapoA-I is cleaved extracellularly by a proapoA-I to plasma apoA-I converting protease. This cleavage generates the plasma apoA-I form which consists of 243 amino acids. Other known apolipoprotein modifications include the modification of apoB, apoC-III, and apoD with carbohydrate chains that contain sialic acid and the proteolytic cleavage of the proapoA-II segment. At the present time we are able to distinguish several isoprotein forms for a particular apolipoprotein. In addition, we began to understand the biochemical changes which lead to a few of these isoproteins. Future research should be directed toward a better understanding not only of the structure but most importantly of the physiological significance of the different apolipoprotein forms.
D000595:Amino Acid Sequence; D001053:Apolipoproteins / Q000097:blood / Q000235:genetics*; D006528:Carcinoma, Hepatocellular; D002460:Cell Line; D002478:Cells, Cultured; D006801:Humans; D008099:Liver / Q000378:metabolism; D008113:Liver Neoplasms; D009924:Organ Culture Techniques; D014176:Protein Biosynthesis; D012333:RNA, Messenger / Q000235:genetics
D001053:Apolipoproteins; D012333:RNA, Messenger