Olivier L M, Krisans S K
Department of Biology, San Diego State University, San Diego, CA 92182, USA.
Biochim Biophys Acta. 2000 Dec 15;1529(1-3):89-102. doi: 10.1016/s1388-1981(00)00139-6.
At least three different subcellular compartments, including peroxisomes, are involved in cholesterol synthesis. Recently, it has been demonstrated that peroxisomes contain a number of enzymes involved in cholesterol biogenesis that previously were considered to be cytosolic or located in the endoplasmic reticulum. Peroxisomes have been shown to contain acetoacetyl-CoA thiolase, HMG-CoA synthase, HMG-CoA reductase, mevalonate kinase, phosphomevalonate kinase, phosphomevalonate decarboxylase, isopentenyl diphosphate isomerase and FPP synthase. Moreover, the activities of these enzymes are also significantly decreased in liver tissue and fibroblast cells obtained from patients with peroxisomal deficiency diseases. In addition, the cholesterol biosynthetic capacity is severely impaired in cultured skin fibroblasts obtained from patients with peroxisomal deficiency diseases. These findings support the proposal that peroxisomes play an essential role in isoprenoid biosynthesis. This paper presents a review of peroxisomal protein targeting and of recent studies demonstrating the localization of cholesterol biosynthetic enzymes in peroxisomes and the identification of peroxisomal targeting signals in these proteins.
至少有三个不同的亚细胞区室，包括过氧化物酶体，参与胆固醇的合成。最近，已经证明过氧化物酶体含有许多参与胆固醇生物合成的酶，这些酶以前被认为是胞质的或位于内质网中。过氧化物酶体已被证明含有乙酰乙酰辅酶A硫解酶、HMG-CoA合酶、HMG-CoA还原酶、甲羟戊酸激酶、磷酸甲羟戊酸激酶、磷酸甲羟戊酸脱羧酶、异戊烯基二磷酸异构酶和FPP合酶。此外，在过氧化物酶体缺乏症患者的肝脏组织和成纤维细胞中，这些酶的活性也显著降低。此外，从过氧化物酶体缺乏症患者获得的培养皮肤成纤维细胞中，胆固醇生物合成能力严重受损。这些发现支持了过氧化物酶体在类异戊二烯生物合成中起重要作用的提议。本文综述了过氧化物酶体蛋白靶向以及最近的研究，这些研究证明了胆固醇生物合成酶在过氧化物酶体中的定位以及这些蛋白中过氧化物酶体靶向信号的鉴定。
