出版社：American Society for Biochemistry and Molecular Biology
摘要：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.
