DECREASED ACTIVATION OF LECITHIN - CHOLESTEROL ACYLTRANSFERASE BY GLYCATED APOLIPOPROTEIN-A-I

Non-enzymatic glycation of plasma proteins may contribute to the exces s risk of developing atherosclerosis in patients with diabetes mellitu s. Glycated apolipoprotein A-I isolated from diabetic subjects was tes ted in vitro for its ability to activate lecithin : cholesterol acyltr ansferase, the principal cholesterol-esterifying enzyme in plasma. Act ivation by glycated apolipoprotein A-I was significantly lower at all concentrations than the activation by normal apolipoprotein A-I. Linea r regression analysis of the kinetic data shows that the ratio app V(m ax)/app K(m) was significantly lower (p < 0.01) for glycated apolipopr otein A-I (0.29 nmol . 1/h . mumol) than for normal apolipoprotein A-I (0.78 nmol . 1/h . mumol). Because lecithin : cholesterol acyltransfe rase provides a driving force in reverse cholesterol transport by este rifying the cellular cholesterol removed by HDL, it is tempting to pos tulate that this abnormal activation may be associated with a reductio n in reverse cholesterol transport and associated with the accelerated development of atherosclerosis in diabetic patients.