Department of Chemistry, The Pennsylvania State University, University Park, PA, USA.
Crit Rev Biochem Mol Biol. 2021 Feb;56(1):1-16. doi: 10.1080/10409238.2020.1832438. Epub 2020 Nov 12.
The focus of this review is the human de novo purine biosynthetic pathway. The pathway enzymes are enumerated, as well as the reactions they catalyze and their physical properties. Early literature evidence suggested that they might assemble into a multi-enzyme complex called a metabolon. The finding that fluorescently-tagged chimeras of the pathway enzymes form discrete puncta, now called purinosomes, is further elaborated in this review to include: a discussion of their assembly; the role of ancillary proteins; their locus at the microtubule/mitochondria interface; the elucidation that at endogenous levels, purinosomes function to channel intermediates from phosphoribosyl pyrophosphate to AMP and GMP; and the evidence for the purinosomes to exist as a protein condensate. The review concludes with a consideration of probable signaling pathways that might promote the assembly and disassembly of the purinosome, in particular the identification of candidate kinases given the extensive phosphorylation of the enzymes. These collective findings substantiate our current view of the de novo purine biosynthetic metabolon whose properties will be representative of how other metabolic pathways might be organized for their function.
这篇综述的重点是人类从头嘌呤生物合成途径。本文列举了途径中的酶，以及它们催化的反应及其物理特性。早期文献证据表明，它们可能组装成一个多酶复合物，称为代谢物。本文进一步详细阐述了荧光标记的途径酶嵌合体形成离散的点状结构，现在称为嘌呤体，包括：讨论它们的组装；辅助蛋白的作用；它们在微管/线粒体界面的位置；阐明在内源性水平上，嘌呤体的功能是将中间体从 5-磷酸核糖焦磷酸转移到 AMP 和 GMP；以及嘌呤体作为蛋白质凝聚物存在的证据。该综述最后考虑了可能促进嘌呤体组装和拆卸的信号通路，特别是鉴于酶的广泛磷酸化，确定候选激酶。这些综合发现证实了我们目前对从头嘌呤生物合成代谢物的看法，其性质将代表其他代谢途径如何为其功能组织。
