ectonucleotidase
{{Purinergic signalling}}
Ectonucleotidases consist of families of nucleotide metabolizing enzymes that are expressed on the plasma membrane and have externally oriented active sites. These enzymes metabolize nucleotides to nucleosides. The contribution of ectonucleotidases in the modulation of purinergic signaling depends on the availability and preference of substrates and on cell and tissue distribution.
Classification
Subfamilies of ectonucleotidases include: CD39/NTPDases (ecto-nucleotide triphosphate diphosphohydrolases), Nucleotide pyrophosphatase/phosphodiesterase (NPP)-type ecto-phosphodiesterases, alkaline phosphatases and ecto-5’-nucleotidases/CD73.{{cite journal|last=Beldi|first=G|author2=Enjyoji, K |author3=Wu, Y |author4=Miller, L |author5=Banz, Y |author6=Sun, X |author7= Robson, SC |title=The role of purinergic signaling in the liver and in transplantation: effects of extracellular nucleotides on hepatic graft vascular injury, rejection and metabolism.|journal=Frontiers in Bioscience|date=Jan 1, 2008|volume=13|issue=13|pages=2588–603|pmid=17981736 |pmc=2892180 |doi=10.2741/2868}}
Function
Ectonucleotidases produce key molecules for purine salvage and consequent replenishment of ATP stores within multiple cell types. Dephosphorylated nucleoside derivatives interact with membrane transporters to enable intracellular uptake. Ectonucleotidases modulate P2 purinergic signaling, and P1 receptors.{{Citation|last1=Kukulski|first1=Filip|title=Chapter 9 - Impact of Ectoenzymes on P2 and P1 Receptor Signaling|date=2011-01-01|url=http://www.sciencedirect.com/science/article/pii/B9780123855268000096|work=Advances in Pharmacology|volume=61|pages=263–299|editor-last=Jacobson|editor-first=Kenneth A.|series=Pharmacology of Purine and Pyrimidine Receptors|publisher=Academic Press|language=en|doi=10.1016/b978-0-12-385526-8.00009-6|access-date=2020-11-28|last2=Lévesque|first2=Sébastien A.|last3=Sévigny|first3=Jean|pmid=21586362|isbn=9780123855268 |editor2-last=Linden|editor2-first=Joel|url-access=subscription}} In addition, ectonucleotidases generate extracellular adenosine, which abrogates nucleotide-mediated effects and activates adenosine receptors, often with opposing (patho-) physiological effects.{{cite journal|last=Roberts|first=V|author2=Stagg, J |author3=Dwyer, KM |title=The Role of Ectonucleotidases CD39 and CD73 and Adenosine Signaling in Solid Organ Transplantation.|journal=Frontiers in Immunology|year=2014|volume=5|pages=64|pmid=24600452|doi=10.3389/fimmu.2014.00064|pmc=3927137|doi-access=free}}
Adenosine generation
The first step in the production of adenosine involves the conversion of ATP/ADP to AMP. It is carried out by ENTPD1, also known as CD39. The second step involves the conversion of AMP to adenosine. It is carried out by NT5E, also known as CD73.{{cite journal|last=Eltzschig|first=Holger K.|author2=Bonney, Stephanie K. |author3=Eckle, Tobias |title=Attenuating myocardial ischemia by targeting A2B adenosine receptors|journal=Trends in Molecular Medicine|date=June 2013|volume=19|issue=6|pages=345–354|doi=10.1016/j.molmed.2013.02.005|pmid=23540714|pmc=3674126}}