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Purinergic signalling |
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![]() Simplified illustration of extracellular purinergic signalling |
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Membrane transporters |
Ectonucleotidases consist of families ofnucleotidemetabolizingenzymes that are expressed on theplasma membrane and have externally oriented active sites. These enzymes metabolizenucleotides tonucleosides. The contribution of ectonucleotidases in the modulation ofpurinergic signaling depends on the availability and preference of substrates and on cell and tissue distribution.[1]
Subfamilies of ectonucleotidases include:CD39/NTPDases (ecto-nucleotide triphosphate diphosphohydrolases), Nucleotide pyrophosphatase/phosphodiesterase (NPP)-type ecto-phosphodiesterases, alkaline phosphatases and ecto-5’-nucleotidases/CD73.[1]
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 modulateP2 purinergic signaling, andP1 receptors.[2] In addition, ectonucleotidases generate extracellular adenosine, which abrogates nucleotide-mediated effects and activates adenosine receptors, often with opposing (patho-) physiological effects.[3]
The first step in the production of adenosine involves the conversion of ATP/ADP to AMP. It is carried out byENTPD1, also known as CD39. The second step involves the conversion of AMP to adenosine. It is carried out byNT5E, also known as CD73.[4]