Tripodi Karina E J, Menendez Bravo Simón M, Cricco Julia A
Departamento de Química Biológica and Instituto de Biología Molecular y Celular de Rosario (IBR, CONICET-UNR), Facultad de Ciencias Bioquímicas y Farmacéuticas, Universidad Nacional de Rosario, Suipacha 531, S2002LRK Rosario, Argentina.
Enzyme Res. 2011;2011:873230. doi: 10.4061/2011/873230. Epub 2011 Apr 10.
Around the world, trypanosomatids are known for being etiological agents of several highly disabling and often fatal diseases like Chagas disease (Trypanosoma cruzi), leishmaniasis (Leishmania spp.), and African trypanosomiasis (Trypanosoma brucei). Throughout their life cycle, they must cope with diverse environmental conditions, and the mechanisms involved in these processes are crucial for their survival. In this review, we describe the role of heme in several essential metabolic pathways of these protozoans. Notwithstanding trypanosomatids lack of the complete heme biosynthetic pathway, we focus our discussion in the metabolic role played for important heme-proteins, like cytochromes. Although several genes for different types of cytochromes, involved in mitochondrial respiration, polyunsaturated fatty acid metabolism, and sterol biosynthesis, are annotated at the Tritryp Genome Project, the encoded proteins have not yet been deeply studied. We pointed our attention into relevant aspects of these protein functions that are amenable to be considered for rational design of trypanocidal agents.
在全球范围内，锥虫被认为是几种极具致残性且往往致命疾病的病原体，如恰加斯病（克氏锥虫）、利什曼病（利什曼原虫属）和非洲锥虫病（布氏锥虫）。在其整个生命周期中，它们必须应对各种环境条件，而这些过程中涉及的机制对其生存至关重要。在本综述中，我们描述了血红素在这些原生动物的几种重要代谢途径中的作用。尽管锥虫缺乏完整的血红素生物合成途径，但我们将讨论重点放在重要的血红素蛋白（如细胞色素）所发挥的代谢作用上。虽然参与线粒体呼吸、多不饱和脂肪酸代谢和甾醇生物合成的不同类型细胞色素的几个基因已在三锥虫基因组计划中注释，但编码的蛋白质尚未得到深入研究。我们将注意力集中在这些蛋白质功能的相关方面，这些方面适合用于设计合理的杀锥虫剂。
