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Journal of Lipid Research, Vol. 45, 2245-2251, December 2004
Copyright © 2004 by American Society for Biochemistry and Molecular Biology

Evidence for altered positional specificity of LCAT in vivo

Papasani V. Subbaiah^1,*,, Jennifer M. Sowa^*, and Michael H. Davidson

^* Departments of Medicine and Biochemistry, University of Illinois at Chicago, Chicago, IL
Molecular Genetics, University of Illinois at Chicago, Chicago, IL
Department of Medicine, Rush University Medical Center, Chicago, IL

¹ To whom correspondence should be addressed. e-mail: psubbaia{at}uic.edu

The percentage of saturated cholesteryl esters (CEs) synthesized by human LCAT is several times higher than expected from the sn-2 acyl composition of plasma phosphatidylcholine (PC), whereas the synthesis of 20:4 CE and 22:6 CE is much lower than expected. To explain these discrepancies, we proposed that LCAT transfers some saturated fatty acids from the sn-1 position of PC species that contain 20:4 or 22:6 at sn-2. The present studies provide in vivo evidence for this hypothesis. We determined the composition and synthesis of CE species in plasma of volunteers before and after a 6 week dietary supplementation with docosahexaenoic acid (22:6; DHA). In addition to an increase in the DHA content of all plasma lipids, there was a significant (+12%; P < 0.005) increase of 16:0 CE, although there was no increase in 16:0 at sn-2 of PC. The increase of DHA in CE was much lower than its increase at sn-2 of PC. Ex vivo synthesis of CE species in plasma showed a significant (+24%; P < 0.005) increase in the synthesis of 16:0 CE after DHA supplementation, which correlated positively with the increase of 22:6, but not of 16:0, at sn-2 of PC.

These results show that the positional specificity of human LCAT is altered when the concentration of 16:0-22:6 PC is increased by DHA supplementation.

Abbreviations: CE, cholesteryl ester; DHA, docosahexaenoic acid; PC, phosphatidylcholine; TG, triacylglycerol

Supplementary key words lecithin:cholesterol acyltransferase • phosphatidylcholine • marine lipids

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