CETP-mediated lipid exchange: LDL gains cholesterol ester

Stable Identifier
R-HSA-266350
Type
Reaction [transition]
Species
Homo sapiens
Compartment
Synonyms
CETP:cholesterol ester complex + LDL <=> LDL:cholesterol ester complex + CETP:triacylglycerol complex
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CETP (cholesterol ester transfer protein) complexed with cholesterol esters interacts with an LDL (low density lipoprotein) particle, acquiring triacylglycerol molecules and donating cholesterol ester to the LDL (Swenson et al. 1988; Morton and Zilversmit 1983). This process is reversible but in the body proceeds in the direction annotated here. A model for the lipid exchange process has been proposed based on recent studies of the structure of CETP:lipid complexes (Qiu et al. 2007).

Apolipoprotein F (APOF) can be associated with HDLs and LDLs. It can inhibit cholesteryl ester transfer protein (CETP) activity, thus inhibiting CETP-mediated transfer events specifically involving the LDL particle (Wang et al. 1999). The function of HDL-associated APOF, which represents >75% of the total plasma pool, is currently unknown. Although over-expression of mouse ApoF can accelerate plasma clearance of HDL (Lagor et al. 2009), physiological levels of ApoF do not affect HDL clearance (Lagor et al. 2012).

Apolipoprotein C-I (APOC1) is an Inhibitor of lipoproteins binding to their respective low density lipoprotein LDL receptor (LDLR), LDL receptor-related protein, and very low density lipoprotein receptor (VLDLR). It directly binds circulating fatty acids therby inhibiting their cellular uptake and is also the major plasma inhibitor of CETP (Westerterp et al. 2007).

Literature References
PubMed ID Title Journal Year
22363685 The effects of apolipoprotein F deficiency on high density lipoprotein cholesterol metabolism in mice

Fields, DW, Drazul-Schrader, D, Rader, DJ, Rothblat, GH, Kumaravel, A, Wu, K, Weintraub, N, Lagor, WR, de la Llera-Moya, M, Khetarpal, SA, Lin, W, Hamm-Alvarez, SF

PLoS ONE 2012
17237796 Crystal structure of cholesteryl ester transfer protein reveals a long tunnel and four bound lipid molecules

Danley, DE, Hoth, LR, Mistry, A, Culp, JS, Ammirati, MJ, Griffor, MC, McGrath, KM, Zhao, H, Wang, IK, Qiu, X, Subashi, AK, Seddon, AP, Freeman, TB, Karam, GA, Hawrylik, SJ, Lloyd, DB, Subashi, TA, Clark, RW, Stutzman-Engwall, KJ, Chrunyk, BA, Cong, Y, Hensley, P, Lira, ME, Hayward, CM, Thompson, JF, Geoghegan, KF

Nat Struct Mol Biol 2007
9880564 Molecular cloning and expression of lipid transfer inhibitor protein reveals its identity with apolipoprotein F

Wang, X, Driscoll, DM, Morton, RE

J. Biol. Chem. 1999
17339654 Apolipoprotein C-I binds free fatty acids and reduces their intracellular esterification

Dahlmans, VE, Jong, MC, Havekes, LM, Offerman, EH, Rensen, PC, Berbée, JF, Westerterp, M, Romijn, JA, Delsing, DJ, Gijbels, MJ

J. Lipid Res. 2007
19008531 Overexpression of apolipoprotein F reduces HDL cholesterol levels in vivo

Billheimer, JT, Rothblat, G, Toh, SA, Rader, DJ, Brown, RJ, Fuki, IV, Lagor, WR, Yuen, T, Millar, JS, de la Llera-Moya, M

Arterioscler. Thromb. Vasc. Biol. 2009
2833496 Plasma cholesteryl ester transfer protein has binding sites for neutral lipids and phospholipids

Brocia, RW, Swenson, TL, Tall, AR

J Biol Chem 1988
6619141 Inter-relationship of lipids transferred by the lipid-transfer protein isolated from human lipoprotein-deficient plasma

Zilversmit, DB, Morton, RE

J Biol Chem 1983
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