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

Abstract

The long-chain fatty acid amides are an emerging family of bioactive lipids with members that include N-acyl amino acids, primary fatty acid amides (PFAMs), N-acylarylalkylamides, N-acylethanolamines, and N-monoacylpolyamines. Fatty acid amides were first identified from biological sources over 50 years ago with the isolation and identification of N-palmitoylethanolamine from egg yolk in 1957 (1) and, in 1965, N-palmitoylethanolamine and N-stearoylethanolamine in several tissues from rat and guinea pig (2). The discovery of N-arachidonoylethanolamine (anandamide) as the endogenous ligand for the mammalian brain cannabinoid receptor CB 1 sparked a dramatic interest in the fatty acid amides (3). Since these early discoveries, a diversity of long-chain fatty acid amides have been identified in mammals and, more recently, in invertebrates as well (4)(5)(6)(7)(8).The N-fatty acylglycines, a subclass of the N-fatty acyl amino acids, are an important class of cell signaling lipids that are distributed throughout the central nervous system and the rest of the body (6, 7, 9). Identification of glycine conjugates dates back to the 1820s with the identification of N-benzoylglycine (hippurate) as a mammalian metabolite (10). N-arachidonoylglycine was the first longchain N-acylglycine identified from a mammalian source and was determined to have anti-nociceptive and antiinflammatory effects in rat models of pain (11). Since

Bm-iAANAT3: Expression and characterization of a novel arylalkylamine N-acyltransferase from Bombyx mori

“…In insects, the iAANATs (iAANATs = insect AANATs) produce N -acetylserotonin, an intermediate in melatonin biosynthesis, and are thought to function in controlling melanism [11,12], the inactivation of biogenic amines [13,14], the sclerotization of the insect cuticle [14,15], and photoperiodism [7]. Our interest in the AANATs is derived from our work on the biosynthesis of the fatty acid amides [16,17], a family of cell signaling lipids [18]. We and others have found that AANAT-like (AANATL) enzymes will catalyze the formation of fatty acid amides from fatty acyl-CoA thioesters and the corresponding amines [17,19–21].…”

“…Our interest in the AANATs is derived from our work on the biosynthesis of the fatty acid amides [16,17], a family of cell signaling lipids [18]. We and others have found that AANAT-like (AANATL) enzymes will catalyze the formation of fatty acid amides from fatty acyl-CoA thioesters and the corresponding amines [17,19–21]. Database searches of insect genomes indicate that a number of iAANATs and iAANATLs could be expressed in a variety of insects [7,14,22].…”

N-Acyl Amino Acids: Metabolism, Molecular Targets, and Role in Biological Processes

“…This pathway accounts also for N-oleoyl glycine (NOleGly) formation [18] as well as for other NAraAAs as cytochrome c-dependent formation of NAraSer, NAraAla, and N-arachidonoyl γ-aminobutyric acid (NAraGABA) from Ara-CoA and the respective amino acids were described [7,17]. In addition, the amide bond formation between medium-and long-chain acyl-CoAs and glycine may be also mediated by glycine N-acyltransferase-like 2 (GLYATL2) and 3 (GLYATL3) described in human [19] and in mouse cells [20] respectively. Indeed, GLYATL2 catalyzed the synthesis of NAGly from acyl-CoA and glycine preferring oleoyl-CoA as a substrate [19] and, reduced levels of N-palmitoyl glycine (NPalGly) and NOleGly were detected in siRNA knockdown of GLYATL3-N18TG2 cells [20].…”

“…In addition, the amide bond formation between medium-and long-chain acyl-CoAs and glycine may be also mediated by glycine N-acyltransferase-like 2 (GLYATL2) and 3 (GLYATL3) described in human [19] and in mouse cells [20] respectively. Indeed, GLYATL2 catalyzed the synthesis of NAGly from acyl-CoA and glycine preferring oleoyl-CoA as a substrate [19] and, reduced levels of N-palmitoyl glycine (NPalGly) and NOleGly were detected in siRNA knockdown of GLYATL3-N18TG2 cells [20]. A second pathway suggested that NAraGly might be generated by oxidative metabolism of the corresponding N-arachidonoyl-ethanolamine via the sequential enzymatic reaction of alcohol dehydrogenase (ADH) and aldehyde dehydrogenase [21,22].…”

GLYAT regulates JNK-mediated cell death in Drosophila

“…GLYAT proteins are specifically localized in the mitochondria 9 , and play pivotal roles in catalyzing the formation of Primary Fatty Acid Amides (PFAMs) 6, 10 , a family of bioactive lipids essential for many biological processes 6, 10, 11 . Anandamide, a member of PFAMs, was shown to activate JNK signaling and promote reactive oxygen species (ROS) formation 12–14 , yet a direct role of GLYAT in JNK signaling and cell death has not been reported.…”