Research Unit for Tropical Diseases, de Duve Institute and Laboratory of Biochemistry, Université catholique de Louvain, Avenue Hippocrate 74, Postal Box B1.74.01, B-1200 Brussels, Belgium.
Mol Microbiol. 2011 Oct;82(1):4-8. doi: 10.1111/j.1365-2958.2011.07810.x. Epub 2011 Sep 2.
NAD+ plays multiple, essential roles in the cell. As a cofactor in many redox reactions it is key in the cellular energy metabolism and as a substrate it participates in many reactions leading to a variety of covalent modifications of enzymes with major roles in regulation of expression and metabolism. Cells may have the ability to produce this metabolite either via alternative de novo synthesis pathways and/or by different salvage pathways. In this issue of Molecular Microbiology, Gazanion et al. (2011) demonstrate that Leishmania species can only rely on the salvage of NAD+ building blocks. One of the enzymes involved, nicotinamidase, is absent from human cells. The enzyme is important for growth of Leishmania infantum and essential for establishing an infection. The crystal structure of the parasite protein has been solved and shows prospects for design of inhibitors to be used as leads for development of new drugs. Indeed, NAD+ metabolism is currently being considered as a promising drug target in various diseases and the vulnerability of Leishmania for interference of this metabolism has been proved in previous work by the same group, by showing that administration of NAD+ precursors has detrimental effect on the pathogenic, amastigote stage of this parasite.
NAD+ 在细胞中发挥多种重要作用。作为许多氧化还原反应的辅助因子，它是细胞能量代谢的关键，作为底物，它参与许多导致酶的各种共价修饰的反应，在表达和代谢的调节中起主要作用。细胞可能具有通过替代从头合成途径和/或通过不同的补救途径来产生这种代谢物的能力。在本期《分子微生物学》中，Gazanion 等人（2011）表明，利什曼原虫物种只能依赖于 NAD+ 构建块的补救。涉及的一种酶，烟酰胺酶，在人体细胞中不存在。该酶对利什曼原虫的生长很重要，对建立感染至关重要。寄生虫蛋白的晶体结构已经解决，为设计抑制剂提供了前景，可作为开发新药的先导。事实上，NAD+ 代谢目前被认为是各种疾病有前途的药物靶点，该组先前的工作已经证明了利什曼原虫对这种代谢的干扰的脆弱性，表明 NAD+ 前体的给药对这种寄生虫的致病性、无鞭毛体阶段有不利影响。
