Evidence that lecithin:cholesterol acyltransferase acts on both high-density and low-density lipoproteins

Abstract

In incubations of plasma containing lipoproteins at physiological concentrations it has been confirmed that high-density lipoproteins (HDL) are the major initial recipients of the esterified cholesterol formed in the reaction catalysed by lecithin:cholesterol acyltransferase. It has also been confirmed, however, that a small proportion of the esterified cholesterol of lecithin:cholesterol acyltransferase origin is incorporated directly into low-density lipoproteins (LDL), via a pathway that bypasses the HDL. This direct incorporation of esterified cholesterol into LDL is compatible with either of two general models. Model A proposes that lecithin:cholesterol acyltransferase does not interact directly with LDL but rather that it acts only on lipoproteins outside the LDL fraction. According to model A, while most of the esterified cholesterol so formed is incorporated into HDL, a small proportion is transferred directly to LDL. Model B, by contrast, proposes that a direct incorporation of esterified cholesterol into LDL is the result of a direct action of lecithin:cholesterol acyltransferase on the free cholesterol associated with LDL. To differentiate between these two models, experiments have been performed in which incubation mixtures containing LDL, HDL and a source of lecithin:cholesterol acyltransferase were supplemented with free [3H]cholesterol which had previously been incorporated into either LDL or HDL. It was found that, of the esterified [3H]cholesterol which was subsequently formed, the proportion recovered in the LDL fraction was much greater in the incubations to which the free [3H]cholesterol had been added as a component of LDL than in those to which it had been added as a component of HDL. This essentially excluded model A but was consistent with model B. It has been concluded that, while most of the lecithin:cholesterol acyltransferase may interact with particles in the HDL fraction, a small proportion of the enzyme interacts directly with LDL.