Reactome | VLDLR binds VLDL

VLDLR binds VLDL

Stable Identifier

R-HSA-8854462

Type

Reaction [binding]

Species

Homo sapiens

Compartment

extracellular region, plasma membrane

ReviewStatus

5/5

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Very low-density lipoproteins (VLDLs) are produced in the liver to transport endogenous triglycerides, phospholipids, cholesterol, and cholesteryl esters in the hydrophilic environment of the bloodstream. They comprise triglycerides (50-60%), cholesterol (10-12%), cholesterol esters (4-6%), phospholipids (18-20%), and apolipoprotein B (8-12%). Of the protein content, two other apolipoproteins are constituents; apolipoprotein C-I (APOC around 20%) (Westerterp et al. 2007) and apolipoprotein C4 (APOC4, minor amount) (Kotite et al. 2003). After release from the liver, circulating VLDL particles can bind very low-density lipoprotein receptors (VLDLR) (Sakai et al. 1994) on extra-hepatic target cells and undergo endocytosis (Go & Mani 2012). VLDL uptake by VLDLR represents a minor contribution towards VLDL metabolism. The majority of VLDL is catalysed by lipoprotein lipase (LPL) which hydrolyses TAGs from VLDL, converting it to intermediate-density lipoprotein (IDL). IDL can be further hydrolysed by hepatic lipase to cholesterol-rich low-density lipoprotein (LDL).

VLDLR consists of five functional domains that resemble the LDL receptor. It is highly expressed in tissues that actively metabolise fatty acids as a source of energy. Binding of VLDLs to VLDLR appears to be inhibited by apolipoprotein C-I (APOC1), therby slowing the clearance of triglyceride-rich lipoproteins from the circulation (Westerterp et al. 2007). The APOE/C1/C4/C2 gene cluster is closely associated with plasma lipid levels, atherosclerotic plaque formation, and thereby implicated in the development of coronary artery disease and Alzheimer’s disease (Xu et al. 2015).

Literature References

PubMed ID	Title	Journal	Year
12700345	Human apoC-IV: isolation, characterization, and immunochemical quantification in plasma and plasma lipoproteins Kotite, L, Zhang, LH, Yu, Z, Burlingame, AL, Havel, RJ	J. Lipid Res.	2003
17339654	Apolipoprotein C-I binds free fatty acids and reduces their intracellular esterification Westerterp, M, Berbée, JF, Delsing, DJ, Jong, MC, Gijbels, MJ, Dahlmans, VE, Offerman, EH, Romijn, JA, Havekes, LM, Rensen, PC	J. Lipid Res.	2007
22461740	Low-density lipoprotein receptor (LDLR) family orchestrates cholesterol homeostasis Go, GW, Mani, A	Yale J Biol Med	2012
8294473	Structure, chromosome location, and expression of the human very low density lipoprotein receptor gene Sakai, J, Hoshino, A, Takahashi, S, Miura, Y, Ishii, H, Suzuki, H, Kawarabayasi, Y, Yamamoto, T	J. Biol. Chem.	1994
26129832	The association of APOC4 polymorphisms with premature coronary artery disease in a Chinese Han population Xu, S, Cheng, J, Li, NH, Chen, YN, Cai, MY, Tang, SS, Huang, H, Zhang, B, Cen, JM, Yang, XL, Chen, C, Liu, X, Xiong, XD	Lipids Health Dis	2015