Kinetics and mechanism of phosphatidylcholine and cholesterol exchange between chylomicrons and high-density lipoproteins.

The exchange of phosphatidylcholine and unesterified cholesterol between rat mesenteric lymph chylomicrons and human high-density lipoproteins was studied in vitro by incubation of radiolabelled chylomicrons (with [N-methyl-14C]phosphatidylcholine and [7(n)-3H]cholesterol) with unlabelled high-density lipoproteins. The kinetic analysis was based on the extent of radioisotope exchange, which was determined by the proportion of label appearing in the high-density lipoprotein elution peak after rapid fractionation on analytical agarose columns. Under our experimental conditions, no net transfer of either phosphatidylcholine or cholesterol is observed. The kinetics of exchange of both phosphatidylcholine and cholesterol are biphasic. Over the first 30 min a maximum of 25% of the phosphatidylcholine and 33% of the cholesterol in chylomicrons exchanges rapidly into the high-density-lipoprotein fraction. Thereafter both lipids continue to exchange for up to 3 h at a much lower rate. For the rapid exchange process the calculated exchange rates for phosphatidylcholine and cholesterol are proportional to the concentrations of both chylomicrons and high-density lipoproteins. The second-order rate constants are (10.5 +/- 0.5) X 10(-5) microM-1 X min-1 for phosphatidylcholine and (32.1 +/- 4.5) X 10(-5) microM-1 X min-1 for cholesterol. The kinetics of the exchange process thus suggest that a significant proportion of both phosphatidylcholine and unesterified cholesterol is rapidly exchangeable between these lipoproteins, and that this exchange is mediated by a 'bimolecular', or collisional, mechanism.