APOLIPOPROTEIN AIMILANO PARTIAL LECITHIN - CHOLESTEROL ACYLTRANSFERASE DEFICIENCY DUE TO LOW-LEVELS OF A FUNCTIONAL ENZYME

The cholesterol esterification process was analyzed in 19 carriers of the apolipoprotein AIMilano (AIM) variant and in 19 age-sex matched controls by measuring lecithin: cholesterol acyltransferase (LCAT) mass, activity (i.e., cholesterol esterification with a standard p in the presence of the endogenous substrate). The AIM subjects had lower LCAT mass (3.30 ± 0.85 μg/ml), activity (71.1 ± 36.4 nmol/ml per h) and cholesterol esterification rate (23.6 ± 12.5 nmol/ml per h) compared to controls (5.22 ± 0.74 μg/ml, 121.6 ± 54.6 nmol/ml0 per h and 53.6 ± 29.9 nmol/ml per h, respectively). The specific LCAT activity, i.e., LCAT activity per μg of LCAT, was similar in the two groups, indicating that the LCAT protein in the AIM carriers is structurally and functionally normal. However, the specific cholesterol esterification rate was 23% lower in the AIM subjects (8.03 ± 6.01 nmol/h per μg) compared to controls (10.49 ± 5.86 nmol/h per μg; P < 0.05). The capacity of HDL3, purified from both AIm and control plasma, to act as substrates for cholesterol esterification was similar, thus suggesting that other mechanism(s) may be in play. Carriers with a relative abundance of abnormal, small HDL3b particles had the most altered cholesterol esterification pattern. Upon evaluating all AIM subjects, a complex relationship between HDL structure, plasma lipid-lipoprotein levels and cholesterol esterification emerged, making the AIMilano condition a unique model for the study of the mechanisms regulating the cholesterol esterification-transfer process in man. © 1990.