Lipidomics: A Corrective Lens for Enzyme Myopia

Classifications and characterizations of specific proteins, such as enzymes, not only allow us to understand biosynthetic and metabolic pathways but they also help to drive our understanding of protein structure and function. How those characterizations are evaluated, however, may change our interpretations and lead us into broader and novel directions in research. Here, we will make the argument that using lipidomics as a tool for characterizing enzymatic function over more traditional toolkit options allows for these types of revelations. Using lipidomics techniques on specific brain regions with a series of enzyme knockout and disease models, we have generated a novel set of analyses from which to view protein function. Through these data, we have demonstrated that NAPE-PLD, MAG lipase, and FAAH all have broader roles throughout the brain than previously thought. Much like the data on how the extinction of specific species within an ecosystem has unpredicted outcomes, so too does the elimination of these enzymes affect the brain lipidome. From a purely biochemical standpoint, it is a fascinating story of how one change in a system can have exponential effects; however, from a drug-target standpoint, it may prove to be a cautionary tale.