Apolipoprotein E Is the Major Physiological Activator of Lecithin−Cholesterol Acyltransferase (LCAT) on Apolipoprotein B Lipoproteins

29 December 2004

journal article
research article
Published by American Chemical Society (ACS) in Biochemistry

Vol. 44 (3) , 1013-1025
https://doi.org/10.1021/bi0481489

Abstract

Our previous studies have indicated that lecithin−cholesterol acyltransferase (LCAT) contributes significantly to the apoB lipoprotein cholesteryl ester (CE) pool. Cholesterol esterification rate (CER) in apoA-I^-^/^-apoE^-^/^- mouse plasma was apoA-I^-^/^-apoE^-^/^- plasma retained ¹/₃ the amount of B6 LCAT activity. This suggested that lack of LCAT enzyme did not explain the low CER in apoA-I^-^/^-apoE^-^/^- mice and indicated that apoE and apoA-I are the only major activators of LCAT in mouse plasma. Deleting apoE on low-density lipoprotein (LDL) reduced CER (1% free cholesterol (FC) esterified/h) compared to B6 (6% FC esterified/h) and apoA-I^-^/^- (11% FC esterified/h) LDL. Similar sized LDL particles from all four genotypes were isolated by fast protein liquid chromatography (FPLC) after radiolabeling with [³H]-free cholesterol (FC). LDLs (1 μg FC) from each genotype were incubated with purified recombinant mouse LCAT; LDL particles from B6 and apoA-I^-^/^- plasma were much better substrates for CE formation (5.7% and 6.3% CE formed/30 min, respectively) than those from apoE^-^/^- and apoE^-^/^-apoA-I^-^/^- plasma (1.2% and 1.1% CE formed/30 min). Western blot analysis showed that the amount of apoA-I on apoE^-^/^- LDLs was higher compared to B6 LDL. Adding apoE to incubations of apoA-I^-^/^-apoE^-^/^- very low density lipoprotein (VLDL) resulted in a 3-fold increase in LCAT CER, whereas addition of apoA-I resulted in a more modest 80% increase. We conclude that apoE is a more significant activator of LCAT than apoA-I on mouse apoB lipoproteins.

Keywords

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