Cell and molecular biology of the assembly and secretion of apolipoprotein B-containing lipoproteins by the liver.
Triglycerides are one of the most efficient storage forms of free energy. Because of their insolubility in biological fluids, their transport between cells and tissues requires that they be assembled into lipoprotein particles. Genetic disruption of the lipoprotein assembly/secretion pathway leads to several human disorders associated with malnutrition and developmental abnormalities. In contrast, patients displaying inappropriately high rates of lipoprotein production display increased risk for the development of atherosclerotic cardiovascular disease. Insights provided by diverse experimental approaches describe an elegant biological adaptation of basic chemical interactions required to overcome the thermodynamic dilemma of producing a stable emulsion vehicle for the transport and tissue targeting of triglycerides. 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 containing a neutral lipid core; and, (2) a lipid transfer protein (microsomal triglyceride transfer protein-MTP). In the endoplasmic reticulum apolipoprotein B has two distinct metabolic fates: (1) entrance into the lipoprotein assembly pathway within the lumen of the endoplasmic reticulum; or, (2) degradation in the cytoplasm by the ubiquitin-dependent proteasome. The destiny of apolipoprotein B is determined by the relative availability of individual lipids and level of expression of MTP. The dynamically varied expression of cholesterol-7alpha-hydroxylase indirectly influences the rate of lipid biosynthesis and the assembly and secretion lipoprotein particles by the liver.
Davis
R A
RA
Mammalian Cell and Molecular Biology Laboratory, Department of Biology, The Molecular Biology Institute, San Diego State University, San Diego, CA 92182-0057, USA. rdavis@sunstroke.sdsu.edu
D001055:Apolipoproteins B / Q000378:metabolism*; D006801:Humans; D008099:Liver / Q000378:metabolism*; D011499:Protein Processing, Post-Translational
D001055:Apolipoproteins B