Cell and molecular biology of the assembly and secretion of apolipoproteinB-containing lipoproteins by the liver

Triglycerides are one of the most efficient storage forms of free energy. B ecause of their insolubility in biological fluids, their transport between cells and tissues requires that they be assembled into lipoprotein particle s. Genetic disruption of the lipoprotein assembly/secretion pathway leads t o several human disorders associated with malnutrition and developmental ab normalities. In contrast, patients displaying inappropriately high rates of lipoprotein production display increased risk for the development of ather osclerotic cardiovascular disease. Insights provided by diverse experimenta l approaches describe an elegant biological adaptation of basic chemical in teractions required to overcome the thermodynamic dilemma of producing a st able emulsion vehicle for the transport and tissue targeting of triglycerid es. The mammalian lipoprotein assembly! secretion pathway shows an absolute requirement for: (1) the unique;amphipathic protein: apolipoprotein B, in a form that is sufficiently large to assemble a lipoprotein particle contai ning a neutral lipid core; and, (2) a lipid transfer protein (microsomal tr iglyceride transfer protein-MTP). In the endoplasmic reticulum apolipoprote in B has two distinct metabolic fates: (1) entrance into the lipoprotein as sembly pathway within the lumen of the endoplasmic reticulum; or, (2) degra dation in the cytoplasm by the ubiquitin-dependent proteasome. The destiny of apolipoprotein B is determined by the relative availability of individua l lipids and level of expression of MTP. The dynamically varied expression of cholesterol-7 alpha-hydroxylase indirectly influences the rate of lipid biosynthesis and the assembly and secretion lipoprotein particles by the li ver. (C) 1999 Elsevier Science B.V. All rights reserved.