N‐Acyl amino acids and their impact on biological processes

Abstract

Over the last two decades a large number of N-long-chain acyl amino acids have been identified in the mammalian body. The pharmacological activities of only a few of them have been investigated and some have been found to be of considerable interest. Thus arachidonoyl serine is vasodilatory and neuroprotective, arachidonoyl glycine is antinociceptive, and oleoyl serine rescues bone loss. However, the pathophysiological/biochemical roles of these amides are mostly unknown.

Functional metagenomic discovery of bacterial effectors in the human microbiome and isolation of commendamide, a GPCR G2A/132 agonist

“…G2A has been implicated in autoimmune disease and atherosclerosis, which are both diseases where host-microbial interactions are thought to play a role (31)(32)(33). The structural similarity between commendamide and a broad class of eukaryotic signaling molecules is striking and suggests that chemical mimicry may be a mechanism used by commensal bacteria to facilitate interactions with their human host (34,35).…”

“…The best studied of these is N-arachidonylethanolamide (anandamide), an endogenous ligand for the cannabinoid GPCR CB1 (57). Other endogenous long-chain N-acyl glycines and ethanolamines are reported to activate diverse receptors including many GPCRs (34,35,58,59). For example, N-arachidonyl-glycine activates GPR18 and T-type calcium channels; N-palmitoyl-ethanolamide activates GPR119, GPR55, and PPARα; and N-palmitoyl-glycine is believed to act through an unidentified GPCR in sensory nerves (Fig.…”

Quantitative profiling of endocannabinoids in lipoproteins by LC–MS/MS

“…Bona fide EC comprise arachidonic acid or arachidonic alcohol moieties conjugated to ethanolamine (in anandamide and virodhamine), glycerol (2-arachidonoylglycerol and noladin ether), or dopamine (Narachidonoyl dopamine). A group of structurally related compounds comprising other fatty acid or fatty alcohol moieties, or even different head groups, for example serine or glycine, is produced in both vertebrate and invertebrate organisms (reviewed in [2,3]). These are less potent ligands of CB 1 and/or CB 2 (and some have no affinity to these receptors at all), and are therefore termed endocannabinoid-related compounds (ERC).…”

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

“…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).…”

“…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).…”