Abstract
The purpose of this study was to test the hypothesis that lipid fluidity regulates lecithin:cholesterol acyltransferase (LCAT) activity. Phosphatidylcholine (PC) species were synthesized that varied in fluidity by changing the number, type (cis vs. trans), or position of the double bonds in 18 or 20 carbon sn-2 fatty acyl chains and recombined with [3H]cholesterol and apolipoprotein A-I to form recombinant high density lipoprotein (rHDL) substrate particles. The activity of purified human plasma LCAT decreased with PC sn-2 fatty acyl chains containing trans versus cis double bonds and as double bonds were moved towards the methyl terminus of the sn-2 fatty acyl chain. The decrease in LCAT activity was significantly correlated with a decrease in rHDL fluidity (measured by diphenylhexatriene fluorescence polarization) for PC species containing 18 carbon (r2 = 0.61, n = 18) and 20 carbon (r2 = 0.93, n = 5) sn-2 fatty acyl chains. rHDL were also made containing 10% of the 18 carbon sn-2 fatty acyl chain PC species and 90% of an inert PC ether matrix (sn-1 18:1, sn-2 16:0 PC ether) to normalize rHDL fluidity. Even though fluidity was similar among the PC ether-containing rHDL, the order of PC reactivity with LCAT was significantly correlated (r2 = 0.71) with that of 100% PC rHDL containing the same 18 carbon sn-2 fatty acyl chain species, suggesting that PC structure in the active site of LCAT determines reactivity in the absence of measurable differences in bilayer fluidity. We conclude that PC fluidity and structure are major regulators of LCAT activity when fatty acyl chain length is constant.—Parks, J. S., K. W. Huggins, A. K. Gebre, and E. R. Burleson. Phosphatidylcholine fluidity and structure affect lecithin:cholesterol acyltransferase activity. J. Lipid Res. 2000. 41: 546–553.
Highlights
The purpose of this study was to test the hypothesis that lipid fluidity regulates lecithin:cholesterol acyltransferase (LCAT) activity
Three of the PC species used in the second experiment contained isomers of eicosatrienoic acid (⌬5,8,11, ⌬8,11,14, and ⌬11,14,17) in the sn-2 position to determine the effect of double bond position on LCAT activity and PC fluidity
These recombinant high density lipoprotein (rHDL) were used to determine whether LCAT reactivity for the 18 carbon sn-2 fatty acyl PC substrates was similar when rHDL fluidity was normalized by the 90% OPPC ether matrix
Summary
The purpose of this study was to test the hypothesis that lipid fluidity regulates lecithin:cholesterol acyltransferase (LCAT) activity. Phosphatidylcholine (PC) species were synthesized that varied in fluidity by changing the number, type (cis vs trans), or position of the double bonds in 18 or 20 carbon sn-2 fatty acyl chains and recombined with [3H]cholesterol and apolipoprotein A-I to form recombinant high density lipoprotein (rHDL) substrate particles. Jonas et al [12] have shown a 100-fold variation in initial reaction velocity of human plasma LCAT among recombinant HDL (rHDL) with PC species consisting of fatty acyl groups that differed in chain length and degree of unsaturation. A study by Jonas and Matz [15] has shown that the gel to liquid-crystalline transition of PC had little impact on the activity of LCAT None of these studies has systematically investigated the effect of lipid fluidity on LCAT reactivity when PC fatty acyl chain length is controlled
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