Activation of lecithin: cholesterol acyltransferase by human apolipoprotein A-IV.
Human plasma apoproteins (apo) A-I and A-IV both activate the enzyme lecithin:cholesterol acyltransferase (EC 2.3.1.43). Lecithin:cholesterol acyltransferase activity was measured by the conversion of [4-14C] cholesterol to [4-14C]cholesteryl ester using artificial phospholipid/cholesterol/[4-14C]cholesterol/apoprotein substrates. The substrate was prepared by the addition of apoprotein to a sonicated aqueous dispersion of phospholipid/cholesterol/[4-14C]cholesterol. The activation of lecithin:cholesterol acyltransferase by apo-A-I and -A-IV differed, depending upon the nature of the hydrocarbon chains of the sn-L-alpha-phosphatidylcholine acyl donor. Apo-A-I was a more potent activator than apo-A-IV with egg yolk lecithin, L-alpha-dioleoylphosphatidylcholine, and L-alpha-phosphatidylcholine substituted with one saturated and one unsaturated fatty acid regardless of the substitution position. When L-alpha-phosphatidylcholine esterified with two saturated fatty acids was used as acyl donor, apo-A-IV was more active than apo-A-I in stimulating the lecithin:cholesterol acyltransferase reaction. Complexes of phosphatidylcholines substituted with two saturated fatty acids served as substrate for lecithin:cholesterol acyltransferase even in the absence of any activator protein. Essentially the same results were obtained when substrate complexes (phospholipid-cholesterol-[4-14C]cholesterol-apoprotein) were prepared by a detergent dialysis procedure. Apo-A-IV-L-alpha-dimyristoylphosphatidylcholine complexes thus prepared were shown to be homogeneous particles by column chromatography and density gradient ultracentrifugation. It is concluded that apo-A-IV is able to facilitate the lecithin:cholesterol acyltransferase reaction in vitro.
D016632:Apolipoprotein A-I; D001054:Apolipoproteins A / Q000097:blood / Q000494:pharmacology*; D002784:Cholesterol / Q000378:metabolism; D002788:Cholesterol Esters / Q000378:metabolism; D004134:Dimyristoylphosphatidylcholine / Q000378:metabolism; D004789:Enzyme Activation / Q000187:drug effects; D004951:Esterification; D005227:Fatty Acids / Q000378:metabolism; D006801:Humans; D007862:Phosphatidylcholine-Sterol O-Acyltransferase / Q000097:blood*; D010713:Phosphatidylcholines / Q000378:metabolism; D013379:Substrate Specificity
D016632:Apolipoprotein A-I; D001054:Apolipoproteins A; D002788:Cholesterol Esters; D005227:Fatty Acids; D010713:Phosphatidylcholines; C022205:apolipoprotein A-IV; D002784:Cholesterol; D007862:Phosphatidylcholine-Sterol O-Acyltransferase; C017251:1,2-oleoylphosphatidylcholine; D004134:Dimyristoylphosphatidylcholine