Nature of the enhancement of lecithin-cholesterol acyltransferase reaction by various apolipoproteins.
The effects of human apolipoproteins on the lecithin-cholesterol acyltransferase reaction were studied by using purified human lecithin-cholesterol acyltransferase and phosphatidylcholine-cholesterol vesicles. When the assay mixtures contained an optimal amount or excess of apo-A-I, the addition of apo-A-II, apo-C-II, apo-C-III1, or apo-C-III2 inhibited the enzymatic reaction. However, at suboptimal apo-A-I concentrations, the addition of low concentrations of these apolipoproteins exhibited activating effects. The relative activating effects were greater at lower apo-A-I levels. Under no circumstance did the combined activating effect of apo-A-I and other apolipoproteins exceed the maximum activating effect observed with the optimal level of apo-A-I alone. Since apo-A-II, apo-C-II, and apo-C-III did not show significant activating effects in the absence of apo-A-I, these apolipoproteins apparently did not act as true activator proteins for the enzymatic reaction. The activation of the enzymatic reaction by apo-A-I alone was shown to be due in part to the enhancement of the enzyme transfer between the substrate particles. The replacement of the transfer-enhancing effect of apo-A-I by apo-A-II, apo-C-II, or apo-C-III appears to be responsible for their apparent activating effects in the presence of suboptimal levels of apo-A-I. These apolipoproteins seemed to coexist with both the enzyme and apo-A-I on the substrate particles under the conditions when they showed the activating effect. However, at the concentrations inhibitory to the enzymatic reaction, these apolipoproteins displaced both the enzyme and apo-A-I from the phosphatidylcholine-cholesterol vesicles.
D016632:Apolipoprotein A-I; D053305:Apolipoprotein C-III; D001053:Apolipoproteins / Q000378:metabolism*; D001054:Apolipoproteins A / Q000494:pharmacology; D001056:Apolipoproteins C / Q000494:pharmacology; D002788:Cholesterol Esters / Q000378:metabolism; D002850:Chromatography, Gel; D006801:Humans; D007862:Phosphatidylcholine-Sterol O-Acyltransferase / Q000378:metabolism*
D016632:Apolipoprotein A-I; D053305:Apolipoprotein C-III; D001053:Apolipoproteins; D001054:Apolipoproteins A; D001056:Apolipoproteins C; D002788:Cholesterol Esters; D007862:Phosphatidylcholine-Sterol O-Acyltransferase