Studies on the Cofactor Requirements for Lecithin: Cholesterol Acyltransferase

Abstract

In 1966 it could be demonstrated by Glomset et al. (2) that the LCAT reaction is the major source of the esterified cholesterol of high density lipopropteins (HDL). It could further be shown that the HDL, subfraction acts as the principal substrate for LCAT, and that the cholesterol ester content of other lipoprotein density classes may be due to lipid exchange. The substrate specificity of LCAT further suggested that the protein part or one of the numerous polypeptides of HDL acts as a necessary cofactor for LCAT. Against the original assumption that no protein cofactor is necessary or that the activity of LCAT is better reflected by the lipid arrangement in phospholipid-cholesterol emulsions, Fielding et al. (1) were the first to demonstrate that apoAl, the major polypeptide of HDL, acts as a necessary cofactor for LCAT. Since this result could not account for several observations to be discussed below, we reinvestigated the cofactor requirements of LCAT. Summarizing the results of this investigation and of other publications, it seems very probable that apoAIII acts as a necessary cofactor for LCAT even if only to bind lysolecithin formed during the enzyme action. The role of apoAI as an additional activator, however, cannot be excluded, since it may render lecithin-cholesterol in an arrangement accessible for LCAT.