Abstract

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.

摘要

本综述的重点是人类从头嘌呤生物合成途径。列举了途径酶，以及它们催化的反应和它们的物理特性。早期的文献证据表明它们可能组装成一种称为代谢子的多酶复合物。在这篇综述中进一步阐述了通路酶的荧光标记嵌合体形成离散斑点（现在称为嘌呤体）这一发现，包括：对其组装的讨论；辅助蛋白的作用；它们在微管/线粒体界面上的位点；阐明在内源性水平上，嘌呤体起到将中间体从磷酸核糖焦磷酸转化为 AMP 和 GMP 的作用；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分解的信号通路，特别是考虑到酶的广泛磷酸化，鉴定候选激酶。这些集体发现证实了我们目前对从头嘌呤生物合成代谢子的看法，其特性将代表其他代谢途径可能如何为其功能组织。