Meta-Biol

• Pathways

LDL (low-density lipoproteins) are complexes of a single molecule of apoprotein B-100 (apoB-100) non-covalently associated with triacylglycerol, free cholesterol, cholesterol esters, and phospholipids.Clearance of LDL from the blood involves binding to LDL receptors associated with coated pits at the cell surface, forming complexes that are internalized and passed via clathrin-coated vesicles to endosomes, where they dissociate. The LDL particles move into lysosomes and are degraded while the LDL receptors are returned to the cell surface. This process occurs in most cell types but is especially prominent in hepatocytes. It plays a major role in returning cholesterol from peripheral tissues to the liver (Hobbs et al. 1990).

Because of their hydrophobicity, lipids are found in the extracellular spaces of the human body primarily in the form of lipoprotein complexes. Chylomicrons form in the small intestine and transport dietary lipids to other tissues in the body. Very low density lipoproteins (VLDL) form in the liver and transport triacylglycerol synthesized there to other tissues of the body. As they circulate, VLDL are acted on by lipoprotein lipases on the endothelial surfaces of blood vessels, liberating fatty acids and glycerol to be taken up by tissues and converting the VLDL first to intermediate density lipoproteins (IDL) and then to low density lipoproteins (LDL). IDL and LDL are cleared from the circulation via a specific cell surface receptor, found in the body primarily on the surfaces of liver cells. High density lipoprotein (HDL) particles, initially formed primarily by the liver, shuttle several kinds of lipids between tissues and other lipoproteins. Notably, they are responsible for the so-called reverse transport of cholesterol from peripheral tissues to LDL for return to the liver.

Three aspects of lipoprotein function are currently annotated in Reactome: chylomicron-mediated lipid transport, LDL endocytosis and degradation, and HDL-mediated lipid transport, each divided into assembly, remodeling, and clearance subpathways.

By definition cells have a critical separation between inner (cytoplasmic) and outer (extracellular) compartments. This separation provides for protection, gradient assembly, and environmental control but at the same time isolates the interior compartments of the cell from energy resources, oxygen, and raw materials. Cells have evolved a myriad of mechanisms to regulate, and enable transportation of small molecules ascross plasma membranes and between cellular organelle compartments within cells.