In vitro glycation of human apolipoprotein AI reduces its efficiency in lecithin:cholesterol acyltransferase activation.

Non-enzymatic glycation of proteins occurs both in vitro and in vivo [l]. This reaction may produce structural, immunological and functional modifications of proteins which could contribute to the pathogenesis of the chronic complications of diabetes mellitus [l-3]. Glycation of HDL apolipoproteins has been demonstrated using an antiglucitollysine monoclonal antibody [4]. Low HDL-cholesterol levels associated with high VLDL and remnant levels is common in diabetic populations [5]. This is probably a multifactorial phenomenon in which impairment of the function of both lipoprotein lipase [LPL] and 1ecithin:cholesterol acyltransferase (LCAT, EC 2.3.1.4.3) may be implicated. In fact, much of apolipoprotein At (apo-AI) is transfered from VLDL to HDL particles. To test the hypothesis that glycation of apo-At could reduce its ability to activate LCAT, we measured LCAT activity with both non-glycated and glycated apo-At as activators, using liposomes containing [i4C]cholesterol as substrate.