Fairlamb A H, Cerami A
Department of Medical Parasitology, London School of Hygiene and Tropical Medicine, United Kingdom.
Annu Rev Microbiol. 1992;46:695-729. doi: 10.1146/annurev.mi.46.100192.003403.
Trypanosomatids differ from all other organisms in their ability to conjugate the sulfur-containing tripeptide, glutathione, and the polyamine, spermidine, to form trypanothione [N1,N8-bis(glutathionyl)spermidine]. Together with the NADPH-dependent flavoprotein, trypanothione reductase, the dithiol form of trypanothione provides an intracellular reducing environment in these parasites, substituting for glutathione and glutathione reductase found in the mammalian host. Trypanothione and its related enzymes are involved in defense against damage by oxidants, certain heavy metals, and possibly xenobiotics. Trypanothione and its metabolic precursor, glutathionylspermidine, are also implicated in the modulation of spermidine levels during growth. Several existing trypanocidal drugs interact with the trypanothione system, suggesting that trypanothione metabolism may be a good target for the development of new drugs. The purification and properties of three key enzymes (glutathionylspermidine synthetase, trypanothione synthetase, and trypanothione reductase) are discussed, and the catalytic mechanism, substrate-specificity, and the three-dimensional structure of trypanothione reductase are compared to that of glutathione reductase.
锥虫与所有其他生物的不同之处在于，它们能够将含硫三肽谷胱甘肽和多胺亚精胺结合，形成锥虫硫醇[N1,N8-双(谷胱甘肽基)亚精胺]。与依赖NADPH的黄素蛋白锥虫硫醇还原酶一起，锥虫硫醇的二硫醇形式在这些寄生虫中提供了细胞内还原环境，替代了哺乳动物宿主中发现的谷胱甘肽和谷胱甘肽还原酶。锥虫硫醇及其相关酶参与抵御氧化剂、某些重金属以及可能的外源化合物造成的损害。锥虫硫醇及其代谢前体谷胱甘肽基亚精胺也与生长过程中亚精胺水平的调节有关。几种现有的杀锥虫药物与锥虫硫醇系统相互作用，这表明锥虫硫醇代谢可能是开发新药的一个良好靶点。文中讨论了三种关键酶（谷胱甘肽基亚精胺合成酶、锥虫硫醇合成酶和锥虫硫醇还原酶）的纯化和特性，并将锥虫硫醇还原酶的催化机制、底物特异性和三维结构与谷胱甘肽还原酶进行了比较。
