purinosome

The purinosome is a proposed dynamic multi-enzyme complex in the cytoplasm of mammalian cells that concentrates the enzymes of de novo purine biosynthesis to accelerate the production of purine nucleotides. It is observed under conditions that limit purine availability, when cells rely on de novo synthesis rather than salvage.

Formation and localization: When purine pools become limiting, certain enzymes of the de novo pathway gather into discrete assemblies, called purinosomes, which often localize in proximity to mitochondria and along microtubules. The assemblies are transient and can disassemble when purine supply is restored. The exact mechanism of assembly is not fully understood, but protein–protein interactions and signaling pathways are implicated.

Composition and function: The purinosome is thought to encompass multiple enzymes catalyzing the steps of de novo purine biosynthesis, which in humans include phosphoribosyl pyrophosphate amidotransferase, GAR synthetase/ transformylase, FGAM synthase, AIR carboxylase, SAICAR synthetase, ADSL, and IMP dehydrogenase among others. By clustering these enzymes, the purinosome is proposed to facilitate substrate channeling and coordinate the flow of intermediates, potentially increasing pathway flux under metabolic stress.

Regulation and significance: Evidence for purinosome formation comes from imaging studies using fluorescently tagged enzymes in cultured human cells. Its formation is influenced by cellular energy status, growth signals, and purine availability. The physiological relevance and prevalence of purinosomes in living organisms remain topics of ongoing research, with some studies supporting a functional role and others calling for further validation.