Franceschini G, Baio M, Calabresi L, Sirtori C R, Cheung M C
Center E. Grossi Paoletti, Institute of Pharmacological Sciences, University of Milan, Italy.
Biochim Biophys Acta. 1990 Mar 12;1043(1):1-6. doi: 10.1016/0005-2760(90)90102-4.
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 proteoliposome substrate) and cholesterol esterification rate (i.e., cholesterol esterification in the presence of the endogenous substrate). The AIM subjects had lower LCAT mass (3.30 +/- 0.85 micrograms/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 micrograms/ml, 121.6 +/- 54.6 nmol/ml per h and 53.6 +/- 29.9 nmol/ml per h, respectively). The specific LCAT activity, i.e., LCAT activity per microgram 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 microgram) compared to controls (10.49 +/- 5.86 nmol/h per microgram; P less than 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.
通过测量卵磷脂胆固醇酰基转移酶（LCAT）的质量、活性（即与标准蛋白脂质体底物的胆固醇酯化）和胆固醇酯化率（即在存在内源性底物的情况下的胆固醇酯化），对19名载脂蛋白AIMilano（AIM）变体携带者和19名年龄性别匹配的对照者的胆固醇酯化过程进行了分析。与对照组（分别为5.22±0.74微克/毫升、121.6±54.6纳摩尔/毫升每小时和53.6±29.9纳摩尔/毫升每小时）相比，AIM受试者的LCAT质量（3.30±0.85微克/毫升）、活性（71.1±36.4纳摩尔/毫升每小时）和胆固醇酯化率（23.6±12.5纳摩尔/毫升每小时）较低。两组的特异性LCAT活性，即每微克LCAT的LCAT活性相似，表明AIM携带者中的LCAT蛋白在结构和功能上是正常的。然而，与对照组（10.49±5.86纳摩尔/小时每微克；P<0.05）相比AIM受试者的特异性胆固醇酯化率低23%（8.03±6.01纳摩尔/小时每微克）。从AIM和对照血浆中纯化的HDL3作为胆固醇酯化底物的能力相似，因此表明可能有其他机制在起作用。具有相对丰富的异常小HDL3b颗粒的携带者的胆固醇酯化模式改变最大。在评估所有AIM受试者后，HDL结构、血浆脂质脂蛋白水平和胆固醇酯化之间出现了复杂的关系，使AIMilano状况成为研究人类胆固醇酯化转移过程调节机制的独特模型。
