The
acyltransferase LCAT mediates FA esterification of plasma
cholesterol. In vitro studies have shown that LCAT also FA-esterifies several
oxysterols, but in vivo evidence is lacking. Here, we measured both free and FA-esterified forms of
sterols in 206 healthy volunteers and 8 individuals with genetic
LCAT deficiency, including familial
LCAT deficiency (FLD) and
fish-eye disease (FED). In the healthy volunteers, the mean values of the
ester-to-total molar ratios of the following
sterols varied: 4β-hydroxycholesterol (4βHC), 0.38; 5,6α-epoxycholesterol (5,6αEC), 0.46; 5,6β-epoxycholesterol (5,6βEC), 0.51;
cholesterol, 0.70; cholestane-3β,5α,6β-triol (CT), 0.70;
7-ketocholesterol (7KC), 0.75;
24S-hydroxycholesterol (24SHC), 0.80;
25-hydroxycholesterol (25HC), 0.81;
27-hydroxycholesterol (27HC), 0.86; and 7α-hydroxycholesterol (7αHC), 0.89. In the individuals with
LCAT deficiency, the plasma levels of the FA-esterified forms of
cholesterol, 5,6αEC, 5,6βEC, CT, 7αHC, 7KC, 24SHC, 25HC, and 27HC, were significantly lower than those in the healthy volunteers. The individuals with FLD had significantly lower FA-esterified forms of 7αHC, 24SHC, and 27HC than those with FED. It is of note that, even in the three FLD individuals with negligible plasma
cholesteryl ester, substantial amounts of the FA-esterified forms of 4βHC, 5,6αEC, 7αHC, 7KC, and 27HC were present. We conclude that LCAT has a major role in the FA esterification of many plasma
oxysterols but contributes little to the FA esterification of 4βHC. Substantial FA esterification of 4βHC, 5,6αEC, 7αHC, 7KC, and 27HC is independent of LCAT.