Reverse cholesterol transport
The reverse cholesterol transport is a pathway in vertebrates in which using HDL ( high density lipoprotein excess) cholesterol from the cells in the body to the liver is transported. It is then dismantled there. So it is part of catabolism . Since too much cholesterol is harmful to the cells, the cholesterol that is transported away and packed in HDL is called good cholesterol .
Single steps
The spherical HDL bound to the HDL receptor (SR-BI) of the liver is broken down into pre-beta-HDL, which circulates again in the blood in a decoupled state and absorbs new cholesterol. Also in the plasma of a precursor using the bone morphogenetic protein 1 (BMP1), a peptidase , the apolipoprotein A1 split.
Transport of cholesterol out of the cell
Apo A1 first binds to a tetramer of the ABCA 1 transporter on the outside of the cell membrane. This complex catalyzes the transport of cholesterol, which is carried in vesicles , out of the cell using ATP . Phospholipids are transported out in the same way . Further Apo A1 from the plasma binds both cholesterol and lipids - a small disk-shaped HDL particle is created. Pre-beta HDL can also form disk HDL with cholesterol and lipids, so HDL is recycled. Another membrane transporter for cholesterol is ABCG1 . The cholesterol transported by ABCG1 collects in puddles on the cell membrane.
Transformation from disc HDL to sphere HDL
The HDL discs, which already contain cholesterol and fat, form a complex with lecithin cholesterol acyltransferase (LCAT). This complex now collects the cholesterol floating in puddles on the membrane and esterifies this and the lipids to cholesterol esters and 2-lysophosphatidylcholine. Then the LCAT separates from HDL again. The now spherical HDL is also called ripe .
On the way to the liver
Before the globular HDL is broken down by the liver, it can undergo various reactions. For example, chylomicrons are able to exchange apolipoprotein CII , -CIII and -E with HDL. HDL can apparently take these up from other cells; Details are not known. HDL also continues to take up cholesterol and lipids, especially from foam cells ; the phospholipid transfer protein (PLTP) plays a role here. Cholesterol esters can be released to LDL via the cholesterol ester transfer protein (CETP) .
Dismantling
HDL particles bind to the HDL receptor (SR-B1) on the outside of the liver . At the same time, HDL is broken down into its components. The exact process is unclear. In any case, pre-beta-HDL is released back into the blood, and cholesterol, cholesterol esters and triacylglycerols are absorbed into the cells. Apo A1 binds to the Cubilin : Amnionless complex and is absorbed via Cubilin endocytosis .
literature
Christopher J. Fielding: High-Density Lipoproteins: From Basic Biology to Clinical Aspects. Wiley-VCH, 2007 ISBN 3527317171
Individual evidence
- ↑ d'Eustachio / Jassal / reactome: HDL-mediated lipid transport
- ↑ d'Eustachio / Jassal / Reactome: Transformation of discoidal HDL to spherical HDL
- ↑ d'Eustachio / Jassal / reactome: Remodeling of spherical HDL
- ↑ d'Eustachio / Jassal / reactome: Disassembly of SR-BI-bound spherical HDL