HDL remodeling

Stable Identifier
R-HSA-8964058
Type
Pathway
Species
Homo sapiens
ReviewStatus
5/5
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HDL (high-density lipoprotein) 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).
ABCG1 mediates the movement of intracellular cholesterol to the extracellular face of the plasma membrane where it is accessible to circulating HDL (Vaughan & Oram 2005). Spherical (mature) HDL particles can acquire additional molecules of free cholesterol (CHOL) and phospholipid (PL) from cell membranes.
At the HDL surface, LCAT (lecithin-cholesterol acyltransferase) associates strongly with HDL particles and, activated by apoA-I, catalyzes the reaction of cholesterol and phosphatidylcholine to yield cholesterol esterified with a long-chain fatty acid and 2-lysophosphatidylcholine. The hydrophobic cholesterol ester reaction product is strongly associated with the HDL particle while the 2-lysophosphatidylcholine product is released. Torcetrapib associates with a molecule of CETP and a spherical HDL particle to form a stable complex, thus trapping CETP and inhibiting CETP-mediated lipid transfer between HDL and LDL (Clark et al. 2006).
Spherical HDL particles can bind apoC-II, apoC-III and and apoE proteins.
Literature References
PubMed ID Title Journal Year
16326978 Description of the torcetrapib series of cholesteryl ester transfer protein inhibitors, including mechanism of action

Cunningham, D, Clark, RW, Ruggeri, RB, Bamberger, MJ

J Lipid Res 2006
18460328 HDL, ABC Transporters, and Cholesterol Efflux: Implications for the Treatment of Atherosclerosis

Yvan-Charvet, L, Wang, N, Pagler, T, Terasaka, N, Tall, AR

Cell Metab 2008
15994327 ABCG1 redistributes cellular cholesterol to domains removable by high density lipoproteins but not by lipid-depleted lipoproteins

Oram, JF, Vaughan, AM

J Biol Chem 2005
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