Editing Anandamide (section)

== Biosynthesis ==
In humans, anandamide is biosynthesized from ''N''-arachidonoyl phosphatidylethanolamine (NAPE). In turn, NAPE arises by transfer of [[arachidonic acid]] from [[lecithin]] to the free amine of [[cephalin]] through an [[N-acyltransferase|''N''-acyltransferase]] enzyme.<ref name="pmid7126608">{{cite journal | vauthors = Natarajan V, Reddy PV, Schmid PC, Schmid HH | title = N-Acylation of ethanolamine phospholipids in canine myocardium | journal = Biochimica et Biophysica Acta (BBA) - Lipids and Lipid Metabolism | volume = 712 | issue = 2 | pages = 342–355 | date = August 1982 | pmid = 7126608 | doi = 10.1016/0005-2760(82)90352-6 }}</ref><ref name="pmid9006968">{{cite journal | vauthors = Cadas H, di Tomaso E, Piomelli D | title = Occurrence and biosynthesis of endogenous cannabinoid precursor, N-arachidonoyl phosphatidylethanolamine, in rat brain | journal = The Journal of Neuroscience | volume = 17 | issue = 4 | pages = 1226–1242 | date = February 1997 | pmid = 9006968 | pmc = 6793739 | doi = 10.1523/JNEUROSCI.17-04-01226.1997 | doi-access = free }}</ref> Anandamide synthesis from NAPE occurs via multiple pathways and includes enzymes such as [[phospholipase A2]], [[phospholipase C]] and [[N-acetylphosphatidylethanolamine-hydrolysing phospholipase D]] (NAPE-PLD),<ref name="Wang_2009" /> with other key enzymes yet to be identified.<ref>{{Cite journal |last=Maccarrone |first=Mauro |date=2017-05-29 |title=Metabolism of the Endocannabinoid Anandamide: Open Questions after 25 Years |url=http://journal.frontiersin.org/article/10.3389/fnmol.2017.00166/full |journal=Frontiers in Molecular Neuroscience |volume=10 |doi=10.3389/fnmol.2017.00166 |issn=1662-5099 |pmc=5447297 |pmid=28611591 |doi-access=free}}</ref>

The crystal structure of NAPE-PLD in complex with [[phosphatidylethanolamine]] and [[deoxycholate]] shows how the [[cannabinoid]] anandamide is generated from membrane [[N-acylphosphatidylethanolamines|''N''-acylphosphatidylethanolamines]] (NAPEs), and reveals that [[bile acids]] – which are mainly involved in the [[Lipid metabolism#Lipid absorption|absorption of lipids]] in the small [[intestine]] – modulate its biogenesis.<ref name="Garau">{{cite journal | vauthors = Magotti P, Bauer I, Igarashi M, Babagoli M, Marotta R, Piomelli D, Garau G | title = Structure of human N-acylphosphatidylethanolamine-hydrolyzing phospholipase D: regulation of fatty acid ethanolamide biosynthesis by bile acids | journal = Structure | volume = 23 | issue = 3 | pages = 598–604 | date = March 2015 | pmid = 25684574 | pmc = 4351732 | doi = 10.1016/j.str.2014.12.018 }}</ref>