Edelstein C, Gordon J I, Vergani C A, Catapano A L, Pietrini V, Scanu A M
J Clin Invest. 1984 Sep;74(3):1098-103. doi: 10.1172/JCI111477.
We examined the ability of the plasma of a 52-yr-old male Tangier patient to effect the conversion of radiolabeled pro-apolipoprotein A-I (apo A-I), isolated from hepatoma cell culture media, into mature apo A-I. The conversion was assessed by amino-terminal sequence analysis, isoform patterns with two-dimensional gel electrophoresis, and a rapid assay based on the different solubilities of intact pro-apo A-I and its hexapeptide prosegment in 10% trichloroacetic acid. We found that the converting activity of Tangier plasma was comparable to that exhibited by control normolipidemic plasma and that in both cases pro-apo A-I was correctly processed at the Gln-Asp bond. After ultracentrifugal fractionation of Tangier plasma at d = 1.21 g/ml, the pro-apo A-I-to-mature apo A-I converting activity was mainly recovered in the middle fraction of d = 1.225 g/ml and was at least 10-fold more effective than the top and bottom fractions. In contrast, in normal plasma the activity was only present in the top and bottom fractions. It has been previously established that in Tangier plasma the pro-apo A-I/apo A-I ratio is significantly higher than normal (1 vs. 0.02). Our studies suggest that this abnormal ratio is not the result of a reduced converting enzyme activity and may relate to differences in turnover rates between Tangier and normal plasma apolipoproteins.
我们检测了一名52岁男性丹吉尔病患者的血浆将从肝癌细胞培养基中分离出的放射性标记前载脂蛋白A-I（apo A-I）转化为成熟apo A-I的能力。通过氨基末端序列分析、二维凝胶电泳的同工型模式以及基于完整前apo A-I及其六肽前体片段在10%三氯乙酸中不同溶解度的快速检测方法来评估这种转化。我们发现，丹吉尔病血浆的转化活性与对照正常血脂血浆的转化活性相当，并且在这两种情况下，前apo A-I在Gln-Asp键处均得到了正确加工。在对丹吉尔病血浆进行d = 1.21 g/ml的超速离心分级分离后，前apo A-I向成熟apo A-I的转化活性主要在d = 1.225 g/ml的中间级分中回收，并且比顶部和底部级分至少有效10倍。相比之下，在正常血浆中，该活性仅存在于顶部和底部级分中。先前已经确定，在丹吉尔病血浆中，前apo A-I/apo A-I的比值显著高于正常水平（1比0.02）。我们的研究表明，这种异常比值并非转化酶活性降低的结果，可能与丹吉尔病血浆和正常血浆载脂蛋白的周转率差异有关。
