Binding Affinity and Reactivity of Lecithin Cholesterol Acyltransferase with Native Lipoproteins

Kosek, Anne Burkybile; Durbin, Diane M.; Jonas, Ana

doi:10.1006/bbrc.1999.0690

Cited by 45 publications

(30 citation statements)

References 15 publications

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“…Several studies indicate that LCAT activity decreases upon enlargement of the HDL particle, particularly on large apoE-rich HDL 1 particles (49)(50)(51)(52). This might be a direct effect of the fact that LCAT is subject to product inhibition ( 45 ), but it has also been suggested that sphingomyelin enrichment of HDL prevents binding of LCAT to the lipoprotein ( 49,53 ). Importantly, upon esterifi cation of cholesterol in HDL, LCAT maintains the gradient of free cholesterol between the cellular membrane and the surface of the HDL particle, which is thought to generate a continuous fl ow of cholesterol from the cell to lipoproteins and prevent the transfer of cholesterol back to the cell (54)(55)(56).…”

Section: Downloaded Frommentioning

confidence: 99%

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Lecithin:cholesterol acyltransferase: old friend or foe in atherosclerosis?

Kunnen

Eck

2012

Journal of Lipid Research

153

124

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Section: Downloaded Frommentioning

confidence: 99%

“…V max /app. K m ) of 100, 16, 1, 6%, respectively ( 45 ). Hence, only a minority of LCAT in the circulation is bound to apoB-containing lipoproteins.…”

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confidence: 98%

Lecithin:cholesterol acyltransferase: old friend or foe in atherosclerosis?

Kunnen

Eck

2012

Journal of Lipid Research

153

124

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“…We suggest that there may be several metabolic advantages to the altered lipid flux among HDL subfractions that occurs in the presence of LTIP. LCAT prefers HDL 3 as a substrate (26) and its activity is stimulated by CETP (10,11), presumably because CETP removes CE and minimizes product inhibition of the enzyme (58). Our studies show that LTIP stimulates this function of CETP, and thus would improve the reactivity of these particles with LCAT.…”

Section: Ltip Binding To Ldl Hdlmentioning

confidence: 99%

“…The two most abundant HDL subpopulations, HDL 2 and HDL 3 , differ not only in terms of particle size, but also in lipid content, lipid/protein ratio, apoprotein A-I/apoprotein A-II ratio, and, presumably, in apoprotein conformation (22)(23)(24)(25). These structural differences of HDL subspecies lead to functional diversity, such as in their interaction with lecithin cholesterol acyltransferase (LCAT) (26,27), hepatic lipase (28 -30), CETP (27,31,32), and the scavenger receptor-BI receptor (33).…”

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confidence: 99%

Lipid Transfer Inhibitor Protein Defines the Participation of High Density Lipoprotein Subfractions in Lipid Transfer Reactions Mediated by Cholesterol Ester Transfer Protein (CETP)

Paromov

Morton

2003

Journal of Biological Chemistry

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Cholesterol ester transfer protein (CETP) moves triglyceride (TG) and cholesteryl ester (CE) between lipoproteins. CETP has no apparent preference for high (HDL) or low (LDL) density lipoprotein as lipid donor to very low density lipoprotein (VLDL), and the preference for HDL observed in plasma is due to suppression of LDL transfers by lipid transfer inhibitor protein (LTIP).Given the heterogeneity of HDL, and a demonstrated ability of HDL subfractions to bind LTIP, we examined whether LTIP might also control CETP-facilitated lipid flux among HDL subfractions. CETP-mediated CE transfers from [ 3 H]CE VLDL to various lipoproteins, combined on an equal phospholipid basis, ranged 2-fold and followed the order: HDL 3 > LDL > HDL 2 . LTIP inhibited VLDL to HDL 2 transfer at one-half the rate of VLDL to LDL. In contrast, VLDL to HDL 3 transfer was stimulated, resulting in a CETP preference for HDL 3 that was 3-fold greater than that for LDL or HDL 2 . Long-term mass transfer experiments confirmed these findings and further established that the previously observed stimulation of CETP activity on HDL by LTIP is due solely to its stimulation of transfer activity on HDL 3 . TG enrichment of HDL 2 , which occurs during the HDL cycle, inhibited CETP activity by ϳ2-fold and LTIP activity was blocked almost completely. This suggests that LTIP keeps lipid transfer activity on HDL 2 low and constant regardless of its TG enrichment status. Overall, these results show that LTIP tailors CETP-mediated remodeling of HDL 3 and HDL 2 particles in subclass-specific ways, strongly implicating LTIP as a regulator of HDL metabolism.Cholesteryl ester transfer protein (CETP) 1 promotes the net transfer of lipids among lipoproteins (1, 2). Because of its unique capacity to mediate net exchange of triglyceride (TG) and cholesteryl ester (CE) between TG-rich VLDL and CE-rich lipoproteins, such as LDL and HDL, CETP plays an essential role in regulating plasma cholesterol levels. By altering lipoprotein core lipid composition, CETP participates in the catabolism of VLDL to LDL (1, 3, 4) and affects the level of LDL subfractions (5-7). Additionally, CETP facilitates HDL metabolism by promoting the formation of larger TG-rich HDL 2 from smaller HDL 3 subspecies (8, 9), stimulating LCAT activity (10, 11), and enhancing the formation of pre␤-HDL (12). These processes influence the reverse transport of peripheral tissue cholesterol to the liver (2,13,14).In a previous study (15), we demonstrated that CETP possesses no functional preference for HDL over LDL. Consequently, in the absence of other factors, LDL is the most active donor of CE to VLDL due to the relative abundance of CE in this lipoprotein in normal plasma. However, CETP activity is controlled by several apolipoproteins including lipid transfer inhibitor protein (LTIP) (15-19). LTIP has been purified and characterized as an acidic glycoprotein with a molecular mass of 33 kDa (17,20). Molecular cloning of LTIP had determined its identity with apolipoprotein F (20). LTIP prevents CETP activi...

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“…8 Subsequent metabolism of these LCATgenerated cholesterol esters is highly species dependent. Unlike mice, rabbits have a lipoprotein metabolism that shows a significant degree of similarity with human lipoprotein metabolism.…”

Section: Introductionmentioning

confidence: 99%