Krisans S K, Ericsson J, Edwards P A, Keller G A
Department of Biology, San Diego State University, California 92182.
J Biol Chem. 1994 May 13;269(19):14165-9.
In this study, we have investigated the subcellular localization of farnesyl-diphosphate synthase (FPP synthase). FPP synthase produces FPP, which is utilized in the synthesis of squalene, cholesterol, farnesylated and geranylgeranylated proteins, dolichols, coenzyme Q, and the isoprenoid moiety of heme a. This enzyme is found in the 100,000 x g supernatant fraction of cells or tissues and has been considered to be a cytoplasmic protein. In this study, analysis of FPP synthase activity and protein in fractionated rat liver together with immunofluorescent and immunoelectron microscopy studies demonstrated unequivocally that FPP synthase is largely localized in peroxisomes. These data, in combination with the previous observation that mevalonate kinase is predominantly localized in peroxisomes, suggest that peroxisomes are the major site of synthesis of FPP from mevalonate. We also demonstrate that in liver tissue obtained from patients with peroxisomal deficiency diseases (Zellweger syndrome and neonatal adrenoleukodystrophy), the activities of five enzymes involved in isoprenoid synthesis, namely mevalonate kinase, phosphomevalonate kinase, mevalonate-diphosphate decarboxylase, isopentenyl-diphosphate isomerase, and FPP synthase, are significantly reduced, consistent with a peroxisomal localization of these enzymes.
在本研究中，我们研究了法尼基二磷酸合酶（FPP合酶）的亚细胞定位。FPP合酶产生FPP，FPP用于角鲨烯、胆固醇、法尼基化和香叶基香叶基化蛋白、多萜醇、辅酶Q以及血红素a的类异戊二烯部分的合成。这种酶存在于细胞或组织的100,000×g上清液组分中，一直被认为是一种细胞质蛋白。在本研究中，对分离的大鼠肝脏中的FPP合酶活性和蛋白质进行分析，并结合免疫荧光和免疫电子显微镜研究，明确证明FPP合酶主要定位于过氧化物酶体。这些数据，结合之前甲羟戊酸激酶主要定位于过氧化物酶体的观察结果，表明过氧化物酶体是由甲羟戊酸合成FPP的主要场所。我们还证明，在患有过氧化物酶体缺乏症（齐-韦综合征和新生儿肾上腺脑白质营养不良）患者的肝脏组织中，参与类异戊二烯合成的五种酶，即甲羟戊酸激酶、磷酸甲羟戊酸激酶、甲羟戊酸二磷酸脱羧酶、异戊烯基二磷酸异构酶和FPP合酶的活性显著降低，这与这些酶定位于过氧化物酶体一致。
