Identification of endogenous acyl amino acids based on a targeted lipidomics approach.

Using a partially purified bovine brain extract, our lab identified three novel endogenous acyl amino acids in mammalian tissues. The presence of numerous amino acids in the body and their ability to form amides with several saturated and unsaturated fatty acids indicated the potential existence of a large number of heretofore unidentified acyl amino acids. Reports of several additional acyl amino acids that activate G-protein coupled receptors (e.

The endocannabinoid anandamide is a precursor for the signaling lipid N-arachidonoyl glycine by two distinct pathways.

Background: N-arachidonoyl glycine (NAGly) is an endogenous signaling lipid with a wide variety of biological activity whose biosynthesis is poorly understood. Two primary biosynthetic pathways have been proposed. One suggests that NAGly is formed via an enzymatically regulated conjugation of arachidonic acid (AA) and glycine.

Targeted lipidomics approach for endogenous N-acyl amino acids in rat brain tissue.

Great effort has been devoted to characterize signaling lipids in central nervous system. This has led to a search for novel strategies to characterize hitherto unknown lipid compositions. Here we developed two methods, one for identification and one for quantification, for N-acyl amino acids, a novel lipid family.

Alcohol dehydrogenase-catalyzed in vitro oxidation of anandamide to N-arachidonoyl glycine, a lipid mediator: synthesis of N-acyl glycinals.

N-Arachidonoyl ethanolamide or anandamide is an endocannabinoid found in most tissues where it acts as an important signaling mediator in a number of physiological and pathophysiological processes. Consequently, intense effort has been focused on understanding all its biosynthetic and metabolic pathways. Herein we report human alcohol dehydrogenase-catalyzed sequential oxidation of anandamide to N-arachidonoyl glycine, a prototypical member of the class of long chain fatty acyl glycines, a new group of lipid mediators with a wide array of physiological effects.

Identification of farnesyl pyrophosphate and N-arachidonylglycine as endogenous ligands for GPR92.

A series of small compounds acting at the orphan G protein-coupled receptor GPR92 were screened using a signaling pathway-specific reporter assay system. Lipid-derived molecules including farnesyl pyrophosphate (FPP), N-arachidonylglycine (NAG), and lysophosphatidic acid were found to activate GPR92. FPP and lysophosphatidic acid were able to activate both G(q/11)- and G(s)-mediated signaling pathways, whereas NAG activated only the G(q/11)-mediated signaling pathway.

N-palmitoyl glycine, a novel endogenous lipid that acts as a modulator of calcium influx and nitric oxide production in sensory neurons.

N-arachidonoyl glycine is an endogenous arachidonoyl amide that activates the orphan G protein-coupled receptor (GPCR) GPR18 in a pertussis toxin (PTX)-sensitive manner and produces antinociceptive and antiinflammatory effects. It is produced by direct conjugation of arachidonic acid to glycine and by oxidative metabolism of the endocannabinoid anandamide. Based on the presence of enzymes that conjugate fatty acids with glycine and the high abundance of palmitic acid in the brain, we hypothesized the endogenous formation of the saturated N-acyl amide N-palmitoyl glycine (PalGly).

Structural analysis of leukotriene C4 isomers using collisional activation and 157 nm photodissociation.

The fragmentation of 5-hydroxy-6-glutathionyl-7,9,11,14-eicosatetraenoic acid [leukotriene C4 or LTC4 (5, 6)] and its isomeric counterpart LTC4 (14, 15) were studied by low and high-energy collisional induced dissociation (CID) and 157 nm photofragmentation. For singly charged protonated LTC4 precursors, photodissociation significantly enhances the signal intensities of informative fragment ions that are very important to distinguish the two LTC4 isomers and generates a few additional fragment ions that are not usually observed in CID experiments. The ion trap enables MSn experiments on the fragment ions generated by photodissociation.

Fatty acyl amides of endogenous tetrahydroisoquinolines are active at the recombinant human TRPV1 receptor.

The SAR of capsazepine revealed that tetrahydroisoquinoline (TIQ) moiety is a core pharmacophore of TRPV1 activity. This implied that conjugates of endogenous TIQs with fatty acids would be active at TRPV1 receptors. Six such compounds were synthesized and tested for calcium mobilization at recombinant TRPV1 receptors overexpressed in HEK293 cells.

Synthesis of 3-substituted quinolines via transition-metal-catalyzed reductive cyclization of o-nitro Baylis-Hillman acetates.

Reductive cyclization of o-nitro-substituted Baylis-Hillman acetates by carbon monoxide, catalyzed by [CpFe(CO)(2)](2), gives moderate to good yields of 3-substituted quinolines.