Glycine N-acyltransferase-like 3 is responsible for long-chain N-acylglycine formation in N18TG2 cells[S]

Long-chain fatty acid amides are signaling lipids found in mammals and other organisms; however, details of the metabolic pathways for the N-acylglycines and primary fatty acid amides (PFAMs) have remained elusive. Heavy-labeled precursor and subtraction lipidomic experiments in mouse neuroblastoma...

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Bibliographic Details
Published in:Journal of lipid research 2016-05, Vol.57 (5), p.781-790
Main Authors: Jeffries, Kristen A., Dempsey, Daniel R., Farrell, Emma K., Anderson, Ryan L., Garbade, Gabrielle J., Gurina, Tatyana S., Gruhonjic, Imran, Gunderson, Carly A., Merkler, David J.
Format: Article
Language:English
Subjects:
Acyltransferases - physiology
Amides - metabolism
Animals
arachidonic acid
brain lipids
Cell Line, Tumor
eicosanoids
Fatty Acids - biosynthesis
Gene Knockdown Techniques
lipids
Lipogenesis
mass spectrometry
Mice
N-acylamide
neuroblastoma cells
oleamide
palmitoylation
siRNA knockdown
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Summary:Long-chain fatty acid amides are signaling lipids found in mammals and other organisms; however, details of the metabolic pathways for the N-acylglycines and primary fatty acid amides (PFAMs) have remained elusive. Heavy-labeled precursor and subtraction lipidomic experiments in mouse neuroblastoma N18TG2 cells, a model cell line for the study of fatty acid amide metabolism, establish the biosynthetic pathways for the N-acylglycines and the PFAMs. We provide evidence that the N-acylglycines are formed by a long-chain specific glycine-conjugating enzyme, glycine N-acyltransferase-like 3 (GLYATL3). siRNA knockdown of GLYATL3 in the N18TG2 cells resulted in a decrease in the levels of the N-acylglycines and the PFAMs. This is the first report of an enzyme responsible for long-chain N-acylglycine production in cellula. The production of the PFAMs in N18TG2 cells was reported to occur by the oxidative cleavage of the N-acylglycines, as catalyzed by peptidylglycine α-amidating monooxygenase (PAM). siRNA knockdown of PAM resulted in an accumulation of [13C18]N-oleoylglycine and decreased levels of [13C18]oleamide when the N18TG2 cells were grown in the presence of [13C18]oleic acid. The addition of [1-13C]palmitate to the N18TG2 cell growth media led to the production of a family of [1-13C]palmitoylated fatty acid amides, consistent with the biosynthetic pathways detailed herein.
ISSN:0022-2275
1539-7262
DOI:10.1194/jlr.M062042