REGULATION OF THE ASSEMBLY AND SECRETION OF VERY-LOW-DENSITY LIPOPROTEINS BY THE LIVER

Recent studies have suggested that there are three sites at which VLDL secretion by the liver may be controlled: (i) Newly synthesised apo-B either remains associated with the RER membrane and is degraded by th e ubiquitin/proteasome system, or is translocated into the lumen and i ncorporated into lipid poor VLDL precursors; (ii) the lumenal apo-B is either degraded or moves on, and (iii) acquires the remaining VLDL li pids in the SER/cis-Golgi. Newly synthesised apo-B, at the cytosolic s ide of the RER, is stabilised and protected from degradation by the ch aperone protein, hsp-70, Triacylglycerol, cholesterol ester and phosph olipids have all been implicated in the translocation of apo-B and mic rosomal triglyceride protein plays a major role. If translocation does not occur then the apo-B is degraded, Dietary fish-oils, but not sunf lower oil, inhibit movement of apo-B containing precursors from the RE R and their assembly with lipids and target lumenal apo-B to degradati on. This effect is reversed by inhibition of lumenal proteolysis, but not by inhibition of cytosolic proteolysis. Therefore lumenal degradat ion of apo-B and secretion appear to be in balance, so that if assembl y of VLDL precursors is slowed, then degradation becomes predominant, If however, degradation is inhibited then VLDL assembly can proceed. T hese observations suggest that movement of VLDL precursors from the RE R lumen to the second stage of assembly may be a further regulated ste p.