Pathway: HDL assembly
Reactions in pathway: HDL assembly :
HDL assembly
HDL particles play a central role in the reverse transport of cholesterol, the process by which cholesterol in tissues other than the liver is returned to the liver for conversion to bile salts and excretion from the body and provided to tissues such as the adrenals and gonads for steroid hormone synthesis (Tall et al. 2008).
HDL particles are heterogeneous and can be fractionated into sub-populations based on their electrophoretic mobility, their density, or their content of various apolipoproteins (Kontush and Chapman 2006). All HDL particles share two key features: they are assembled on a protein scaffold provided by apolipoprotein A-I (apoA-I), and they are recycled to allow a net flow of lipids from peripheral tissues to the liver and steroidogenic tissues while allowing apoA-I molecules to be re-used.
Here, the assembly of nascent (discoidal) HDL particles on newly synthesized apoA-I, a process that in the body occurs primarily in the liver, and the loading of discoidal HDL with additional lipid through interaction with cells carrying excess cholesterol (transformation to spherical HDL) are annotated.
HDL particles are heterogeneous and can be fractionated into sub-populations based on their electrophoretic mobility, their density, or their content of various apolipoproteins (Kontush and Chapman 2006). All HDL particles share two key features: they are assembled on a protein scaffold provided by apolipoprotein A-I (apoA-I), and they are recycled to allow a net flow of lipids from peripheral tissues to the liver and steroidogenic tissues while allowing apoA-I molecules to be re-used.
Here, the assembly of nascent (discoidal) HDL particles on newly synthesized apoA-I, a process that in the body occurs primarily in the liver, and the loading of discoidal HDL with additional lipid through interaction with cells carrying excess cholesterol (transformation to spherical HDL) are annotated.
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.