title: Metabolomics annotates ABHD3 as a physiologic regulator of medium-chain phospholipids.
abstract: 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 α/β-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.
authors.affiliation: The Scripps Research Institute, La Jolla, California, USA.
authors.forename: Jonathan Z
authors.initials: JZ
authors.lastname: Long
authors.forename: Justin S
authors.initials: JS
authors.lastname: Cisar
authors.forename: David
authors.initials: D
authors.lastname: Milliken
authors.forename: Sherry
authors.initials: S
authors.lastname: Niessen
authors.forename: Chu
authors.initials: C
authors.lastname: Wang
authors.forename: Sunia A
authors.initials: SA
authors.lastname: Trauger
authors.forename: Gary
authors.initials: G
authors.lastname: Siuzdak
authors.forename: Benjamin F
authors.initials: BF
authors.lastname: Cravatt
mesh_terms: D000818:Animals; D005786:Gene Expression Regulation / Q000502:physiology; D015971:Gene Expression Regulation, Enzymologic; D057809:HEK293 Cells; D006801:Humans; D006867:Hydrolases / Q000235:genetics / Q000378:metabolism*; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D055432:Metabolomics / Q000379:methods*; D051379:Mice; D018345:Mice, Knockout; D054467:Phospholipases A2; D010743:Phospholipids / Q000737:chemistry / Q000378:metabolism*; D054852:Small Molecule Libraries; D013379:Substrate Specificity
chemical_list: D008565:Membrane Proteins; D010743:Phospholipids; D054852:Small Molecule Libraries; D006867:Hydrolases; C454241:Abhd3 protein, mouse; D054467:Phospholipases A2