The John Curtin School of Medical Research, Australian National University Canberra, Australian Capital Territory, Australia. Philip.Board @anu.edu.au
Drug Metab Rev. 2011 May;43(2):226-35. doi: 10.3109/03602532.2011.561353.
The omega class of glutathione transferases (GSTs) is a relatively ancient member of the cytosolic GST superfamily, and the omega-class GSTs are found in plants, animals, and some microbial species. The omega-class GSTs exhibit the canonical GST fold, but, unlike other GSTs, the omega-class GSTs have a cysteine residue in their active site. Consequently, the omega-class GSTs catalyze a range of thiol transferase and reduction reactions that are not catalyzed by members of the other classes. Human GSTO1-1 can catalyze the reduction of monomethylarsonic acid (V), but this does not appear to be physiologically important in cases of high environmental arsenic exposure. GSTO1-1 also plays an important role in the biotransformation of reactive α-haloketones to nontoxic acetophenones. Genetic variation is common in the omega-class GST genes, and variants that result in deficiency of GSTO1-1 have been characterized. Genetic linkage studies have discovered associations between GSTO genes and the age at onset of Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis. The mechanism underlying this association with neurological disease may derive from the capacity of omega-class GSTs to mitigate oxidative stress or their role in activating the proinflammatory cytokine, interleukin-1β.
ω 类谷胱甘肽 S-转移酶（GSTs）是细胞溶质 GST 超家族中相对古老的成员，ω 类 GSTs 存在于植物、动物和一些微生物物种中。ω 类 GSTs 具有典型的 GST 折叠结构，但与其他 GSTs 不同的是，ω 类 GSTs 在其活性位点含有半胱氨酸残基。因此，ω 类 GSTs 催化一系列硫转移酶和还原反应，而这些反应不能被其他类别的 GSTs 催化。人 GSTO1-1 可以催化单甲基砷酸（V）的还原，但在高环境砷暴露的情况下，这似乎在生理上并不重要。GSTO1-1 在活性α-卤代酮向无毒苯乙酮的生物转化中也起着重要作用。ω 类 GST 基因中的遗传变异很常见，并且已经对 GSTO1-1 缺乏的变异进行了表征。遗传连锁研究发现 GST 基因与阿尔茨海默病、帕金森病和肌萎缩侧索硬化症的发病年龄之间存在关联。这种与神经疾病相关的机制可能源于 ω 类 GSTs 减轻氧化应激的能力，或其激活促炎细胞因子白细胞介素-1β的作用。
