5nucleotidases

5'-nucleotidases are enzymes that hydrolyze 5'-phosphorylated nucleotides to nucleosides and inorganic phosphate, thereby regulating intracellular and extracellular nucleotide pools and adenosine signaling. They play a central role in purine metabolism and nucleotide salvage, influencing energy balance and signaling pathways in various tissues.

Two major classes exist. Ecto-5'-nucleotidases are cell-surface or extracellular enzymes, exemplified by CD73, which is GPI-anchored and encoded by the NT5E gene. CD73 converts AMP to adenosine and phosphate, contributing to local adenosine production in many tissues. Cytosolic 5'-nucleotidases, including NT5C1 and NT5C2, function inside the cell to regulate intracellular nucleotide pools and salvage pathways, thereby maintaining balance among nucleotides and affecting cellular metabolism.

Physiological and pathological roles are linked to adenosine formation and nucleotide homeostasis. The adenosine produced by ecto-enzymes acts on P1 receptors (A1, A2A, A2B, A3) and modulates inflammation, vascular tone, and immune responses. In cancer, increased CD73 activity can promote immunosuppression and tumor progression by elevating extracellular adenosine. Cytosolic 5'-nucleotidases help control nucleotide availability for DNA and RNA synthesis and can influence responses to metabolic stress.

Regulation and clinical relevance are active areas of research. Expression of ecto-5'-nucleotidases is influenced by hypoxia and cytokines, among other factors. Inhibitors of CD73, including antibodies and small molecules, are being explored as cancer therapies and as treatments for inflammatory or ischemic conditions. 5'-nucleotidases are also studied as biomarkers in certain diseases due to their roles in nucleotide signaling and metabolism.