文章基本信息

标题：Absence of functional peroxisomes does not lead to deficiency of enzymes involved in cholesterol biosynthesis
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作者：Sietske Hogenboom ; Gerrit Jan Romeijn ; Sander M. Houten 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：2002
卷号：43
期号：1
页码：90-98
语种：English
出版社：American Society for Biochemistry and Molecular Biology
摘要：To unravel the conflicting data concerning the dependence of human cholesterol biosynthesis on functional peroxisomes, we determined activities and levels of selected enzymes involved in cholesterol biosynthesis in livers of PEX5 knockout mice, a well-characterized model for human Zellweger syndrome. We found that all enzymes measured, including putative peroxisomal enzymes, are at least as active in the peroxisome-deficient Zellweger mice as in control mice, indicating that mislocalization of enzymes to the cytosol does not lead to decreased activity or degradation. Prompted by these results, we re-examined this aspect in human subjects by specific enzyme activity measurements and immunoblotting with highly specific antisera. Our results show that the previously reported deficiencies of mevalonate kinase and phosphomevalonate kinase activity in livers from human Zellweger patients reflect the bad condition of the livers, rather than mislocalization to the cytosol. Our data provide an explanation for the conflicting findings in the literature and show that great care should be taken in the interpretation of data obtained in postmortem material. —Hogenboom, S., G. J. Romeijn, S. M. Houten, M. Baes, R. J. A. Wanders, and H. R. Waterham. Absence of functional peroxisomes does not lead to deficiency of enzymes involved in cholesterol biosynthesis. J. Lipid Res. 2002. 43: 90–98.
关键词：3-hydroxy-3-methylglutaryl coenzyme A reductase ; isopentenyl pyrophosphate isomerase ; isoprenoids ; mevalonate kinase ; mevalonate pyrophosphate decarboxylase ; PEX5 mouse ; phosphomevalonate kinase ; Δ⁷-sterol reductase ; Zellweger syndrome