Influence of Serum Amyloid A on Human Lecithin : Cholesterol Acyltransferase Activity
Lecithin: cholesterol acyltransferase (EC 22.214.171.124, LCAT) is responsible for the formation of the bulk of cholesteryl ester in plasma by transferring a fatty acid group from the carbon-2 position of phosphatidylcholine to the 3-hydroxyl group of unesterified cholesterol. The LCAT-reaction requires an apoprotein as activator and besides apolipoprotein (apo) AI several other potent apoproteins (AIV, E and CI) were identified as activators.
As Serum Amyloid A (SAA) was shown to also be an apolipoprotein mainly associated with high density lipoprotein (HDL) we tested its potention to activate LCAT.
LCAT activity was measured by conversion of (4-14C)-cholesterol to (4-14C)-cholesteryl ester using artificial dimyristorylglycerophospho-choline (DMPC)/cholesterol/(4-14)-cholesterol/apolipoprotein substrates. The substrates were prepared either by a detergent dialysis procedure or by addition of apoprotein to a sonicated aqueous dispersion of lipid. In addition two different molar ratios of apoprotein: phospholipid (PC) (1:50 and 1: 310) were chosen at a constant molar ratio of total cholesterol: PC of 1:20. The various substrates were incubated with purified LCAT enzyme at 37°C
DMPC or egg yolk lecithin/cholesterol (4-14C)-cholesterol/SAA complexes per se did not stimulate LCAT activity significantly. However apo SAA incorporated together with apo AI by the detergent dialysis procedure lead to a marked increase in cholesteryl ester formation as compared to apo AI alone. The known stimulating effect of apo All together with apo AI on LCAT activity was used as control. The degree of activation depended upon the molar ratio of apo SAA and apo AI. Thus a twofold increase in cholesteryl ester formation occured at equal molar ratios.
We conclude that apo SAA together with apo AI modulates LCAT activity in vitro. We postulate that apo SAA also influences HDL metabolism in vivo.
KeywordsCholesteryl Ester Cholesterol Acyltransferase LCAT Activity Density Gradient Ultracentrifugation Unesterified Cholesterol
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