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.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Gene Expression Regulation / physiology
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Gene Expression Regulation, Enzymologic
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HEK293 Cells
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Humans
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Hydrolases / genetics
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Hydrolases / metabolism*
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Membrane Proteins / genetics
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Membrane Proteins / metabolism*
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Metabolomics / methods*
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Mice
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Mice, Knockout
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Phospholipases A2
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Phospholipids / chemistry
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Phospholipids / metabolism*
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Small Molecule Libraries
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Substrate Specificity
Substances
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Membrane Proteins
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Phospholipids
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Small Molecule Libraries
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Hydrolases
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Abhd3 protein, mouse
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Phospholipases A2
Associated data
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PubChem-Substance/125092044
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PubChem-Substance/125092045
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PubChem-Substance/125092046
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PubChem-Substance/125092047
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PubChem-Substance/125092048
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PubChem-Substance/125092049
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PubChem-Substance/125092050
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PubChem-Substance/125092051
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PubChem-Substance/125092052
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PubChem-Substance/125092053
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PubChem-Substance/125092054
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PubChem-Substance/125092055