Division of Endocrinology, Diabetes and Clinical Nutrition, Department of Medicine, Oregon Health & Science University, Portland, Oregon, USA.
Atherosclerosis. 2010 Jan;208(1):155-60. doi: 10.1016/j.atherosclerosis.2009.07.031. Epub 2009 Jul 23.
Cholesterol is esterified in mammals by two enzymes: LCAT (lecithin cholesterol acyltransferase) in plasma and ACAT(1) and ACAT(2) (acyl-CoA cholesterol acyltransferases) in the tissues. We hypothesized that the sterol structure may have significant effects on the outcome of esterification by these enzymes. To test this hypothesis, we analyzed sterol esters in plasma and tissues in patients having non-cholesterol sterols (sitosterolemia and Smith-Lemli-Opitz syndrome). The esterification of a given sterol was defined as the sterol ester percentage of total sterols. The esterification of cholesterol in plasma by LCAT was 67% and in tissues by ACAT was 64%. Esterification of nine sterols (cholesterol, cholestanol, campesterol, stigmasterol, sitosterol, campestanol, sitostanol, 7-dehydrocholesterol and 8-dehydrocholesterol) was examined. The relative esterification (cholesterol being 1.0) of these sterols by the plasma LCAT was 1.00, 0.95, 0.89, 0.40, 0.85, 0.82 and 0.80, 0.69 and 0.82, respectively. The esterification by the tissue ACAT was 1.00, 1.29, 0.75, 0.49, 0.45, 1.21 and 0.74, respectively. The predominant fatty acid of the sterol esters was linoleic acid for LCAT and oleic acid for ACAT. We compared the esterification of two sterols differing by only one functional group (a chemical group attached to sterol nucleus) and were able to quantify the effects of individual functional groups on sterol esterification. The saturation of the A ring of cholesterol increased ester formation by ACAT by 29% and decreased the esterification by LCAT by 5.9%. Esterification by ACAT and LCAT was reduced, respectively, by 25 and 11% by the presence of an additional methyl group on the side chain of cholesterol at the C-24 position. This data supports our hypothesis that the structure of the sterol substrate has a significant effect on its esterification by ACAT or LCAT.
血浆中的 LCAT（卵磷脂胆固醇酰基转移酶）和组织中的 ACAT（1）和 ACAT（2）（酰基辅酶 A 胆固醇酰基转移酶）。我们假设固醇结构可能对这些酶的酯化结果有重大影响。为了验证这一假设，我们分析了患有非胆固醇固醇（植物固醇血症和 Smith-Lemli-Opitz 综合征）的患者的血浆和组织中的固醇酯。给定固醇的酯化定义为总固醇中固醇酯的百分比。LCAT 对血浆中胆固醇的酯化率为 67%，ACAT 对组织中胆固醇的酯化率为 64%。研究了九种固醇（胆固醇、胆甾醇、菜油固醇、豆固醇、谷固醇、菜油甾醇、谷甾烷醇、7-脱氢胆固醇和 8-脱氢胆固醇）的酯化作用。这些固醇由血浆 LCAT 进行酯化的相对酯化率（胆固醇为 1.0）分别为 1.00、0.95、0.89、0.40、0.85、0.82 和 0.80、0.69 和 0.82。由组织 ACAT 进行酯化的相对酯化率分别为 1.00、1.29、0.75、0.49、0.45、1.21 和 0.74。LCAT 的固醇酯的主要脂肪酸为亚油酸，ACAT 的主要脂肪酸为油酸。我们比较了只有一个功能基团（连接在固醇核上的化学基团）差异的两种固醇的酯化作用，并能够定量分析单个功能基团对固醇酯化作用的影响。胆固醇 A 环的饱和程度使 ACAT 的酯化作用增加了 29%，使 LCAT 的酯化作用减少了 5.9%。胆固醇侧链 C-24 位上增加一个甲基基团分别使 ACAT 和 LCAT 的酯化作用减少了 25%和 11%。这些数据支持我们的假设，即固醇底物的结构对其与 ACAT 或 LCAT 的酯化作用有重大影响。
