欧米伽类谷胱甘肽转移酶变异体的单甲基胂酸还原酶和脱氢抗坏血酸还原酶活性的表征:对砷代谢和阿尔茨海默病和帕金森病发病年龄的影响
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笨蛋EM，董事会PG, Whitbread AK, Tetlow N, Cavanaugh JA, Blackburn AC, Masoumi A
欧米伽类谷胱甘肽转移酶变异体的单甲基胂酸还原酶和脱氢抗坏血酸还原酶活性的表征:对砷代谢和阿尔茨海默病和帕金森病发病年龄的影响
Pharmacogenet Genomics. 2005 july;15(7):493-501。
- PubMed ID
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15970797 (PubMed视图］
- 摘要
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人体内有两个功能性的Omega类谷胱甘肽转移酶(GST)基因。GSTO1具有多个编码区等位基因的多态性，包括A140D的替换，E155的潜在缺失和E208K的替换。GSTO2也是多态的，在编码区有N142D替代。我们研究了这些变化对酶的硫转移酶、脱氢抗坏血酸还原酶、单甲基胂酸还原酶和二甲基胂酸还原酶活性的影响。用ni -琼脂糖亲和层析法纯化大肠杆菌中的变异蛋白。GSTO2-2是不溶性的，必须从8 M尿素中溶解并重新折叠。GSTO1-1中A140D和E208K的取代没有改变比活性。E155的缺失导致每种底物的比活性增加2 - 3倍。这种缺失也导致酶的热稳定性显著下降。E155缺失与异常的砷排泄模式有关; however, the available data do not clearly identify the cause of this abnormality. We found that GSTO2-2 has activity with the same substrates as GSTO1-1, and the dehydroascorbate reductase activity of GSTO2-2 is approximately 70-100-fold higher than that of GSTO1-1. The polymorphic N142D substitution had no effect on the specific activity of the enzyme with any substrate. The most notable feature of GSTO2-2 was its very high dehydroascorbate reductase activity, which suggests that GSTO2-2 may significantly protect against oxidative stress by recycling ascorbate. A defect in ascorbate metabolism may provide a common mechanism by which the Omega class GSTs influence the age-at-onset of Alzheimer's and Parkinson's diseases.