文章基本信息

标题：In vitro expression of natural mutants of human lecithin:cholesterol acyltransferase.
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作者：S J Qu ; H Z Fan ; F Blanco-Vaca 等
期刊名称：JLR Papers In Press
印刷版ISSN：0022-2275
电子版ISSN：1539-7262
出版年度：1995
卷号：36
期号：5
页码：967-974
语种：English
出版社：American Society for Biochemistry and Molecular Biology
摘要：Fish-eye disease (FED) and familial lecithin:cholesterol acyltransferase (LCAT) deficiency (FLD) are rare disorders of lipid metabolism linked to mutations in the LCAT gene. Eleven LCAT cDNA constructs associated with FED and FLD were prepared by site-directed mutagenesis and expressed in COS-6 cells. Analysis of total RNA from wild-type, FED, and FLD transfectants revealed that all contained LCAT-specific mRNA. Western blot analysis demonstrated that all LCAT transfectants synthesized LCAT. Mean LCAT secretion by FED transfectants was slightly lower than secretion by wild-type transfectants, whereas secretion by FLD transfectants was much lower. The specific activities of FED and FLD LCAT against model high density lipoproteins were 6% and 11%, respectively, of wild-type activity. The ratios of the LCAT activities against low density lipoproteins to those against model high density lipoproteins decreased in the order FED mutants > FLD mutants approximately wild type. FED and FLD LCAT mutants are different: the former are more active against low density lipoproteins, and the latter are less secretion-competent. The greater reactivity of FED LCAT against low density lipoproteins may explain the relative mildness of the clinical manifestations of FED compared to those of FLD.