Okumiya T, Ishii S, Takenaka T, Kase R, Kamei S, Sakuraba H, Suzuki Y
Department of Clinical Genetics, Tokyo Metropolitan Institute of Medical Science, Japan.
Biochem Biophys Res Commun. 1995 Sep 25;214(3):1219-24. doi: 10.1006/bbrc.1995.2416.
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.
在COS-1细胞表达系统和成淋巴细胞中研究了半乳糖对导致法布里病的α-半乳糖苷酶错义突变体的影响。三种突变酶A156V、L166V和Q279E在半乳糖培养的COS-1细胞中活性和含量增加。另一种无催化活性的突变体C142Y则无任何变化。在用半乳糖培养的成淋巴细胞中，具有A156V、L166V、G260A和G373S各自突变的四名典型法布里病患者以及具有Q279E、R301Q和M296I各自突变的三名非典型法布里病患者的酶活性显著增加。而在分别具有C142Y、E66Q/R112C、G328R和N320K的其他四名典型法布里病患者中未观察到这种增加。这表明，导致法布里病的α-半乳糖苷酶基因中的许多错义突变，无论临床表型如何，都能表达具有催化活性的突变酶，这些酶在生理条件下会迅速降解，而半乳糖可使其稳定。
