Pedley Anthony M, Benkovic Stephen J
Department of Chemistry, The Pennsylvania State University, University Park, PA 16802, USA.
Department of Chemistry, The Pennsylvania State University, University Park, PA 16802, USA.
Trends Biochem Sci. 2017 Feb;42(2):141-154. doi: 10.1016/j.tibs.2016.09.009. Epub 2016 Oct 28.
Other than serving as building blocks for DNA and RNA, purine metabolites provide a cell with the necessary energy and cofactors to promote cell survival and proliferation. A renewed interest in how purine metabolism may fuel cancer progression has uncovered a new perspective into how a cell regulates purine need. Under cellular conditions of high purine demand, the de novo purine biosynthetic enzymes cluster near mitochondria and microtubules to form dynamic multienzyme complexes referred to as 'purinosomes'. In this review, we highlight the purinosome as a novel level of metabolic organization of enzymes in cells, its consequences for regulation of purine metabolism, and the extent that purine metabolism is being targeted for the treatment of cancers.
除了作为DNA和RNA的组成成分外，嘌呤代谢产物还为细胞提供促进细胞存活和增殖所需的能量及辅助因子。对嘌呤代谢如何推动癌症进展的重新关注，揭示了细胞如何调节嘌呤需求的新视角。在细胞对嘌呤需求较高的情况下，从头合成嘌呤的生物合成酶会在线粒体和微管附近聚集，形成被称为“嘌呤体”的动态多酶复合物。在本综述中，我们强调嘌呤体是细胞中酶代谢组织的一个新层次，其对嘌呤代谢调节的影响，以及嘌呤代谢作为癌症治疗靶点的程度。
