Galactose stabilizes various missense mutants of α-galactosidase in Fabry disease
Galactose stabilizes various missense mutants of α-galactosidase in Fabry disease
复制标题
半乳糖稳定法布里病中 α-半乳糖苷酶的各种错义突变体
DOI：
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发表时间：
1995
期刊：
影响因子：
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通讯作者：
Yoshiyuki Suzuki
中科院分区：
文献类型：
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作者：
T. Okumiya;S. Ishii;T. Takenaka;R. Kase;S. Kamei;H. Sakuraba;Yoshiyuki Suzuki
在COS-1细胞表达系统和成淋巴细胞中研究了半乳糖对引起法布里病的α-半乳糖苷酶错义突变体的影响。三种突变酶A156 V、L166 V和Q279 E在半乳糖培养的COS-1细胞中表现出活性和量的增加。另一个没有催化活性的突变体C142 Y没有显示出任何变化。在与半乳糖培养的淋巴母细胞中，酶活性在具有相应突变A156 V、L166 V、G260 A和G373 S的四个典型法布里病患者中显著增加，并且在具有相应突变Q279 E、R301 Q和M296 I的三个非典型法布里病患者中显著增加。在其他四名典型法布里病患者中未观察到这种增加，分别为C142 Y，E66 Q/R112 C，G328 R和N320 K。这表明引起法布里病的α-半乳糖苷酶基因中的许多错义突变允许催化活性突变酶的表达，而不管临床表型如何，其在生理条件下迅速降解并被半乳糖稳定。
The effect of galactose on alpha-galactosidase missense mutants causing Fabry disease was investigated in the COS-1 cell expression system and lymphoblasts. Three mutant enzymes, A156V, L166V and Q279E, showed increases in activity and amount in COS-1 cells cultured with galactose. Another mutant without catalytic activity, C142Y, did not show any changes. In lymphoblasts cultured with galactose, the enzyme activity increased significantly in four classical Fabry patients with the respective mutations, A156V, L166V, G260A and G373S, and in three atypical Fabry patients with the respective mutations, Q279E, R301Q and M296I. Such an increase was not observed in the other four classical Fabry patients, with C142Y, E66Q/R112C, G328R and N320K, respectively. This suggests that many missense mutations in the alpha-galactosidase gene causing Fabry disease allow the expression of catalytically active mutant enzymes regardless of the clinical phenotype, which are rapidly degraded under physiological conditions and stabilized by galactose.