Biology of endocannabinoid synthesis system

Prostaglandins Other Lipid Mediat. 2009 Sep;89(3-4):112-9. doi: 10.1016/j.prostaglandins.2008.12.002. Epub 2008 Dec 14.

Abstract

Endocannabinoids (endogenous ligands of cannabinoid receptors) exert diverse physiological and pathophysiological functions in animal tissues. N-Arachidonoylethanolamine (anandamide) and 2-arachidonoylglycerol (2-AG) are two representative endocannabinoids. Both the compounds are arachidonic acid-containing lipid molecules generated from membrane glycerophospholipids, but their biosynthetic pathways are totally different. Anandamide is principally formed together with other N-acylethanolamines (NAEs) in a two-step pathway, which is composed of Ca(2+)-dependent N-acyltransferase and N-acylphosphatidylethanolamine-hydrolyzing phospholipase D (NAPE-PLD). cDNA cloning of NAPE-PLD and subsequent analysis of its gene-disrupted mice led to the discovery of alternative pathways comprising multiple enzymes. As for the 2-AG biosynthesis, recent results, including cDNA cloning of diacylglycerol lipase and analyses of phospholipase Cbeta-deficient mice, demonstrated that these two enzymes are responsible for the in vivo formation of 2-AG functioning as a retrograde messenger in synapses. In this review article, we will focus on recent progress in the studies on the enzymes responsible for the endocannabinoid biosyntheses.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Acyltransferases / metabolism
  • Amidohydrolases / metabolism
  • Animals
  • Arachidonic Acid / metabolism
  • Arachidonic Acids / biosynthesis*
  • Cannabinoid Receptor Modulators / biosynthesis*
  • Endocannabinoids*
  • Female
  • Glycerides / biosynthesis*
  • Humans
  • Isoenzymes
  • Lipoprotein Lipase / metabolism
  • Male
  • Phospholipase D / metabolism
  • Polyunsaturated Alkamides
  • Pregnancy
  • Signal Transduction
  • Type C Phospholipases / metabolism

Substances

  • Arachidonic Acids
  • Cannabinoid Receptor Modulators
  • Endocannabinoids
  • Glycerides
  • Isoenzymes
  • Polyunsaturated Alkamides
  • Arachidonic Acid
  • glyceryl 2-arachidonate
  • Acyltransferases
  • Lipoprotein Lipase
  • Type C Phospholipases
  • Phospholipase D
  • Amidohydrolases
  • NAAA protein, human
  • anandamide