Altered positional specificity of human plasma lecithin-cholesterol acyltransferase in the presence of sn-2 arachidonoyl phosphatidyl cholines. Mechanism of formation of saturated cholesteryl esters.
The positional specificity of purified human lecithin-cholesterol acyltransferase (LCAT) was studied by analyzing the labeled cholesteryl ester (CE) species formed in the presence of proteoliposome substrates containing mixed chain phosphatidylcholine (PC) species, labeled cholesterol and apoprotein A-I. Whereas over 90% of the acyl groups used for CE synthesis were derived from the sn-2 position of most of the naturally occurring PC substrates, about 75% of the CE species formed in the presence of sn-1-myristoyl 2-arachidonoyl PC, sn-1-palmitoyl-2-arachidonoyl (PAPC) and sn-1-palmitoyl 2-docosahexaenoyl PC were derived from the sn-1-position. On the other hand, rat LCAT utilized mostly sn-2-acyl group from either PAPC or from sn-1-palmitoyl 2-linoleoyl PC. The positional specificity of the human enzyme was not affected by the alteration in the matrix fluidity, type of the apoprotein activator used, or by the free cholesterol/PC ratio in the substrate. These results show that the positional specificity of human plasma LCAT is altered in the presence of sn-2-arachidonoyl PC, or sn-2-docosahexaenoyl PC, probably due to steric restrictions at the active site, and this may account for the formation of disproportionately high concentrations of saturated CE, and low concentrations of long-chain polyunsaturated CE in human plasma, relative to the composition of sn-2-acyl groups in plasma PC.
Subbaiah
P V
PV
Department of Medicine, Rush Medical College, Chicago, IL.
Liu
M
M
Bolan
P J
PJ
Paltauf
F
F
D000818:Animals; D001095:Arachidonic Acids / Q000378:metabolism*; D002788:Cholesterol Esters / Q000097:blood / Q000378:metabolism*; D002851:Chromatography, High Pressure Liquid; D006801:Humans; D008560:Membrane Fluidity; D007862:Phosphatidylcholine-Sterol O-Acyltransferase / Q000097:blood* / Q000302:isolation & purification; D010713:Phosphatidylcholines / Q000378:metabolism*; D051381:Rats; D013379:Substrate Specificity
D001095:Arachidonic Acids; D002788:Cholesterol Esters; D010713:Phosphatidylcholines; D007862:Phosphatidylcholine-Sterol O-Acyltransferase