Exploring Metabolic Pathways and Regulation through Functional Chemoproteomic and Metabolomic Platforms

•Chemoproteomic approaches can be used to assess the functional state of enzymes•Chemoproteomic approaches can be used to develop inhibitors for enzymes•Metabolomics can be used to assign biochemical function of enzymes•Metabolic pathways can control post-translational and epigenetic regulation

Genome sequencing efforts have revealed a strikingly large number of uncharacterized genes, including poorly or uncharacterized metabolic enzymes, metabolites, and metabolic networks that operate in normal physiology, and those enzymes and pathways that may be rewired under pathological conditions. Although deciphering the functions of the uncharacterized metabolic genome is a challenging prospect, it also presents an opportunity for identifying novel metabolic nodes that may be important in disease therapy. In this review, we will discuss the chemoproteomic and metabolomic platforms used in identifying, characterizing, and targeting nodal metabolic pathways important in physiology and disease, describing an integrated workflow for functional mapping of metabolic enzymes.