All organisms, including humans, possess a huge number of uncharacterized enzymes. Here we describe a general cell-based screen for enzyme substrate discovery by untargeted metabolomics and its application to identify the protein alpha/beta-hydrolase domain-containing 3 (ABHD3) as a lipase that selectively cleaves medium-chain and oxidatively truncated phospholipids. Abhd3(-/-) mice possess elevated myristoyl (C14)-phospholipids, including the bioactive lipid C14-lysophosphatidylcholine, confirming the physiological relevance of our substrate assignments.
Long JZ, Cisar JS, Milliken D, Niessen S, Wang C, Trauger SA, Siuzdak G, Cravatt BF (2011) Metabolomics annotates ABHD3 as a physiologic regulator of medium-chain phospholipids Nat Chemical Biology7: 763-5
Long JZ, Cisar JS, Milliken D, Niessen S, Wang C, Trauger SA, Siuzdak G, Cravatt BF (2011) Nat Chemical Biology7: 763-5