Centro de Química e Bioquímica, Departamento de Química e Bioquímica, Faculdade de Ciências da Universidade de Lisboa, Portugal.
Int J Med Microbiol. 2012 Oct;302(4-5):225-9. doi: 10.1016/j.ijmm.2012.07.005. Epub 2012 Aug 14.
The glyoxalase system is the main catabolic route for methylglyoxal, a non-enzymatic glycolytic byproduct with toxic and mutagenic effects. This pathway includes two enzymes, glyoxalase I and glyoxalase II, which convert methylglyoxal to d-lactate by using glutathione as a catalytic cofactor. In protozoan parasites the glyoxalase system shows marked deviations from this model. For example, the functional replacement of glutathione by trypanothione (a spermidine-glutathione conjugate) is a characteristic of trypanosomatids. Also interesting are the lack of glyoxalase I and the presence of two glyoxalase II enzymes in Trypanosoma brucei. In Plasmodium falciparum the glyoxalase pathway is glutathione-dependent, and glyoxalase I is an atypical monomeric enzyme with two active sites. Although it is tempting to exploit these differences for their potential therapeutic value, they provide invaluable clues regarding methylglyoxal metabolism and the evolution of protozoan parasites. Glyoxalase enzymes have been characterized in only a few protozoan parasites, namely Plasmodium falciparum and the trypanosomatids Leishmania and Trypanosoma. In this review, we will focus on the key features of the glyoxalase pathway in major human protozoan parasites, with particular emphasis on the characterized systems in Plasmodium falciparum, Trypanosoma brucei, Trypanosoma cruzi, and Leishmania spp. We will also search for genes encoding glyoxalase I and II in Toxoplasma gondii, Entamoeba histolytica, and Giardia lamblia.
糖氧还蛋白系统是甲基乙二醛（一种具有毒性和致突变作用的非酶糖酵解副产物）的主要分解途径。该途径包括两种酶，即糖氧还酶 I 和糖氧还酶 II，它们利用谷胱甘肽作为催化辅因子将甲基乙二醛转化为 D-乳酸。在原生动物寄生虫中，糖氧还蛋白系统显示出明显偏离该模型的特征。例如，谷胱甘肽被三肽硫（一种亚精胺-谷胱甘肽结合物）功能替代是鞭毛原生动物的特征。同样有趣的是，缺乏糖氧还酶 I 和在布氏锥虫中有两种糖氧还酶 II 酶的存在。在恶性疟原虫中，糖氧还酶途径依赖于谷胱甘肽，糖氧还酶 I 是一种具有两个活性位点的非典型单体酶。尽管利用这些差异具有潜在的治疗价值，但它们为甲基乙二醛代谢和原生动物寄生虫的进化提供了宝贵的线索。糖氧还酶已在少数原生动物寄生虫中得到了表征，即恶性疟原虫和锥虫科的利什曼原虫和锥虫。在这篇综述中，我们将重点介绍主要人类原生动物寄生虫中糖氧还酶途径的关键特征，特别强调恶性疟原虫、布氏锥虫、克氏锥虫和利什曼原虫中已表征的系统。我们还将搜索编码糖氧还酶 I 和 II 的基因在刚地弓形虫、溶组织内阿米巴和蓝氏贾第鞭毛虫中的存在。
