A mechanistic model of lecithin:cholesterol acyltransferase activity exploits discoidal HDL composition and structure

► LCAT penetration and acyl-enzyme formation determine enzyme activity in discoidal HDL. ► Cholesterol as a nucleophilic agent determines its esterification rate. ► Adjustment for phospholipid level is required to derive kinetic constants. ► Cholesterol influences the unfolding pattern of individual apoA-I domains. ► Substrate activation by apoA-I may include ester bond exposure to LCAT active center.