Steenkamp Daniel J
Division of Chemical Pathology, Department of Laboratory Medicine, University of Cape Town Medical School, Observatory 7925, South Africa.
Antioxid Redox Signal. 2002 Feb;4(1):105-21. doi: 10.1089/152308602753625906.
Leishmania and Trypanosoma are two genera of the protozoal Order Kinetoplastida that cause widespread diseases of humans and their livestock. The production of reactive oxygen and nitrogen intermediates by the host plays an important role in the control of infections by these organisms. Signal transduction and its redox regulation have not been studied in any depth in trypanosomatids, but homologs of the redox-sensitive signal transduction machinery of other eukaryotes have been recognized. These include homologs of activator protein-1, human apurinic endonuclease 1 (Ref-1) endonuclease, iron-responsive protein, protein kinases, and phosphatases. The detoxification of peroxide is catalyzed by a trypanothione-dependent system that has no counterpart in mammals, and thus ranks as one of the biochemical peculiarities of trypanosomatids. There is substantial evidence that trypanothione is essential for the survival of Trypanosoma brucei and for the virulence of Leishmania spp. Apart from trypanothione and its precursors, trypanosomatids also possess significant amounts of N(1)-methyl-4-mercaptohistidine or ovothiol A, but its function in the trypanosomatids is not presently understood. The biosynthesis of ovothiol A in Crithidia fasciculata proceeds by addition of sulfur from cysteine to histidine to form 4-mercaptohistidine. S-(4'-L-Histidyl)-L-cysteine sulfoxide is the transsulfuration intermediate. 4-Mercaptohistidine is subsequently methylated with S-adenosylmethionine as the likely methyl donor.
利什曼原虫和锥虫是原生动物动质体目的两个属，可引发人类及其家畜的广泛疾病。宿主产生的活性氧和氮中间体在控制这些生物体的感染中起着重要作用。在锥虫中尚未对信号转导及其氧化还原调节进行深入研究，但已识别出其他真核生物的氧化还原敏感信号转导机制的同源物。这些包括激活蛋白-1、人脱嘌呤内切核酸酶1（Ref-1）内切核酸酶、铁反应蛋白、蛋白激酶和磷酸酶的同源物。过氧化物的解毒由一种依赖于锥虫硫醇的系统催化，该系统在哺乳动物中不存在，因此是锥虫的生化特性之一。有大量证据表明，锥虫硫醇对于布氏锥虫的存活和利什曼原虫属的毒力至关重要。除了锥虫硫醇及其前体，锥虫还含有大量的N(1)-甲基-4-巯基组氨酸或卵硫醇A，但其在锥虫中的功能目前尚不清楚。在束状短膜虫中，卵硫醇A的生物合成是通过将半胱氨酸中的硫添加到组氨酸中形成4-巯基组氨酸进行的。S-(4'-L-组氨酰)-L-半胱氨酸亚砜是转硫作用中间体。4-巯基组氨酸随后以S-腺苷甲硫氨酸作为可能的甲基供体进行甲基化。
