A New View into the Regulation of Purine Metabolism: The Purinosome

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. Following its discovery, the purinosome presents itself as a new form of enzyme organization within de novo purine biosynthesis. Mechanisms surrounding purinosome assembly and disassembly have provided insights into how purine metabolism is regulated within cells. The classification of the purinosome as a metabolon brings to light whether enzyme clustering is a commonly employed regulatory mechanism used by cells to meet their bioenergetics and biomolecular demands. Elucidating the mechanisms of purine metabolism deregulation in diseases, such as cancer, has brought forth the potential to develop new therapeutic strategies.