Meta-Biol

• Pathways

Very low-density lipoprotein (VLDL) is synthesised in the liver in two steps. First, apolipoprotein B-100 (APOB-100) is co- and post-translationally lipidated in the rough ER lumen. After transfer to the smooth ER lumen, lipidated APOB-100 acquires lipids to become bona fide VLDL. Lipid composition of VLDL - triglycerides (50-60%), cholesterol (10-12%), cholesterol esters (4-6%), phospholipids (18-20%), and apolipoprotein B (8-12%). When VLDL assembly is complete, it travels along the Golgi apparatus to be eventually secreted from the liver into general circulation. In circulation, VLDL can acquire more lipoproteins. At least two other apolipoproteins are constituents; apolipoprotein C-I (APOC1, around 20%) and apolipoprotein C4 (APOC4, minor amount) (Gibbons et al. 2004; Olofsson et al. 2000).

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.