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. We also present a straightforward synthesis for a series of N-acyl glycinals including N-arachidonoyl glycinal, an intermediate in the alcohol dehydrogenase-catalyzed oxidation of anandamide.

Graphical abstractHuman alcohol dehydrogenase-catalyzed metabolism of endocannabinoid anandamide to N-arachidonoyl glycinal and N-arachidonoyl glycine and a straightforward synthesis of a series of N-acyl glycinals which are intermediates in these ADH-catalyzed oxidation reactions are presented.Figure optionsDownload full-size imageDownload as PowerPoint slide