Evidence for altered positional specificity of LCAT in vivo: studies with docosahexaenoic acid feeding in humans

• Published in: Journal of lipid research Vol. 45; no. 12; p. 2245
• Main Authors: Subbaiah, Papasani V, Sowa, Jennifer M, Davidson, Michael H
• Format: Journal Article
• Language: English
• Published: United States 01.12.2004
• Subjects: Docosahexaenoic Acids - metabolism; Humans; Lipids - blood; Phosphatidylcholine-Sterol O-Acyltransferase - metabolism; Substrate Specificity
• ISSN: 0022-2275
• DOI: 10.1194/jlr.M400197-JLR200

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.