BIOSYNTHESIS OF 2 MOLECULAR-FORMS CERULOPLASMIN IN RAT-LIVER - POLAR SECRETION INTO BLOOD AND BILE

This work was undertaken to elucidate the role of ceruloplasmin (CP) i n the distribution, transport, and clearance of copper. Biosynthesis a nd secretion of CP in rat liver were studied The topography. of intrac ellular transport and secretion of CP was studied in pulse-chase exper iments. The synthesis of cp was confined to membrane-bound polyribosom es; newly synthesized molecules were found in association with the end oplasmic reticulum membranes. In a separate series of experiments cath eters were inserted into the right carotid artery and the common bile duct of each rat. This approach demonstrated that the secretion of cp was polar: two distinct molecular farms of the protein were detected, which differed both in the rate of secretion and in physicochemical pr operties. The slowly secreted isoform corresponded to serum CP; its ra pidly secreted counterpart was found in bile. Liver slices incubated u nder conditions favoring protein synthesis and secretion released into the medium S-35CP. The secretion appeared as a two-stage process: a similar to 200 kD CP-like protein was released within 30 min of incub ation; CP (similar to 130 kD molecular weight) appeared in the medium 2 h later. A possible physiological role of biliary CP and its implica tions in Wilson's disease are discussed.