Ectonucleotidase
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Ectonucleotidases consist of families of
nucleotide Nucleotides are organic molecules consisting of a nucleoside and a phosphate. They serve as monomeric units of the nucleic acid polymers – deoxyribonucleic acid (DNA) and ribonucleic acid (RNA), both of which are essential biomolecules wi ...
metabolizing Metabolism (, from el, μεταβολή ''metabolē'', "change") is the set of life-sustaining chemical reactions in organisms. The three main functions of metabolism are: the conversion of the energy in food to energy available to run cell ...
enzymes Enzymes () are proteins that act as biological catalysts by accelerating chemical reactions. The molecules upon which enzymes may act are called substrate (chemistry), substrates, and the enzyme converts the substrates into different molecule ...
that are expressed on the plasma membrane and have externally oriented active sites. These enzymes metabolize
nucleotide Nucleotides are organic molecules consisting of a nucleoside and a phosphate. They serve as monomeric units of the nucleic acid polymers – deoxyribonucleic acid (DNA) and ribonucleic acid (RNA), both of which are essential biomolecules wi ...
s to
nucleoside Nucleosides are glycosylamines that can be thought of as nucleotides without a phosphate group. A nucleoside consists simply of a nucleobase (also termed a nitrogenous base) and a five-carbon sugar (ribose or 2'-deoxyribose) whereas a nucleotide ...
s. 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 5′-nucleotidase (5′-NT), also known as ecto-5′-nucleotidase or CD73 (cluster of differentiation 73), is an enzyme that in humans is encoded by the ''NT5E'' gene. CD73 commonly serves to convert AMP to adenosine. Transcription factor bindi ...
.


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. In addition, ectonucleotidases generate extracellular adenosine, which abrogates nucleotide-mediated effects and activates adenosine receptors, often with opposing (patho-) physiological effects.


Adenosine generation

The first step in the production of adenosine involves the conversion of ATP/ADP to AMP. It is carried out by
ENTPD1 Ectonucleoside triphosphate diphosphohydrolase-1 (gene: ''ENTPD1''; protein: NTPDase1) also known as CD39 (Cluster of Differentiation 39), is a typical cell surface enzyme with a catalytic site on the extracellular face. Function NTPDase1 is an ...
, also known as CD39. The second step involves the conversion of AMP to adenosine. It is carried out by
NT5E 5′-nucleotidase (5′-NT), also known as ecto-5′-nucleotidase or CD73 (cluster of differentiation 73), is an enzyme that in humans is encoded by the ''NT5E'' gene. CD73 commonly serves to convert AMP to adenosine. Transcription factor bindi ...
, also known as CD73.


References

Hydrolases Purinergic signalling {{Enzyme-stub