Activity-based proteomic and metabolomic approaches for understanding metabolism

•There are many enzymatic pathways that remain uncharacterized in the human genome.•Activity-based proteomics globally assesses enzyme activities.•Activity-based proteomics can be used for inhibitor discovery of enzymes.•Metabolomics can dissect enzyme function in complex living systems.

There are an increasing number of human pathologies that have been associated with altered metabolism, including obesity, diabetes, atherosclerosis, cancer, and neurodegenerative diseases. Most attention on metabolism has been focused on well-understood metabolic pathways and has largely ignored most of the biochemical pathways that operate in (patho)physiological settings, in part because of the vast landscape of uncharacterized and undiscovered metabolic pathways. One technology that has arisen to meet this challenge is activity-based protein profiling (ABPP) that uses activity-based chemical probes to broadly assess the functional states of both characterized and uncharacterized enzymes. This review will focus on how ABPP, coupled with inhibitor discovery platforms and functional metabolomic technologies, have led to discoveries that have expanded our knowledge of metabolism in health and disease.

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