Diverse strategies adopted by nature for regulating purine biosynthesis via fine-tuning of purine metabolic enzymes

Abstract

Purine nucleotides, generated by de novo synthesis and salvage pathways, are essential for metabolism and act as building blocks of genetic material. To avoid an imbalance in the nucleotide pool, nature has devised several strategies to regulate/tune the catalytic performance of key purine metabolic enzymes. Here, we discuss some recent examples, such as stress-regulating alarmones that bind to select pathway enzymes, huge ensembles like dynamic metabolons and self-assembled filaments that highlight the layered fine-control prevalent in the purine metabolic pathway to fulfill requisite purine demands. Examples of enzymes that turn-on only under allosteric control, are regulated via long-distance communication that facilitates transient conduits have additionally been explored.

Keywords: Alarmones; Conformational flexibility; Filaments; Purine metabolism; Purine salvage pathway; Purinosome; de novo purine biosynthetic pathway.