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Glycine N-acyltransferase-like 3 Is Responsible for Long-Chain N-acylglycine Formation in N18TG2 Cells

Kristen A Jeffries, Daniel R Dempsey, Emma K Farrell, Ryan L Anderson, Gabrielle J Garbade, Tatyana S Gurina, Imran Gruhonjic, Carly A Gunderson, David J Merkler

J Lipid Res. 2016 May;57(5):781-90.

PMID: 27016726

Abstract:

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 [(13)C18]N-oleoylglycine and decreased levels of [(13)C18]oleamide when the N18TG2 cells were grown in the presence of [(13)C18]oleic acid. The addition of [1-(13)C]palmitate to the N18TG2 cell growth media led to the production of a family of [1-(13)C]palmitoylated fatty acid amides, consistent with the biosynthetic pathways detailed herein.

Chemicals Related in the Paper:

Catalog Number Product Name Structure CAS Number Price
AP2601903 N-Oleoylglycine N-Oleoylglycine 2601-90-3 Price
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