nucleotidases

Nucleotidases are enzymes that catalyze the hydrolysis of nucleotides, removing phosphate groups to form nucleosides and inorganic phosphate. In metabolism, they help regulate intracellular and extracellular pools of nucleotides and nucleosides, substances used in RNA and DNA synthesis as well as in signaling pathways mediated by purinergic receptors.

Nucleotidases occur in multiple cellular locations. Some are membrane-bound or secreted (ecto-nucleotidases) and act on extracellular nucleotides, while others reside inside cells in the cytosol or organelles. A well-characterized extracellular enzyme is ecto-5'-nucleotidase, commonly called CD73, which converts AMP to adenosine and can influence inflammation, vascular function, and immune responses. Cytosolic members such as NT5C1 and NT5C2 regulate intracellular nucleoside monophosphate pools and contribute to nucleotide salvage.

Enzymatic mechanisms of nucleotidases typically involve metalloenzymes that use divalent cations, such as Mg2+ or Mn2+, to activate water for nucleophilic attack on the phosphomonoester bond. Substrate specificities vary, with some nucleotidases preferring AMP and others acting on multiple nucleotides.

Physiological and clinical relevance: Nucleotidase activity shapes nucleotide signaling and energy balance. CD73-generated adenosine can modulate immune responses, vascular tone, and tissue protection, and alterations in nucleotidase expression or activity have been linked to cancer, inflammatory diseases, and metabolic disorders. Inhibitors or modulators of nucleotidases are being explored for therapeutic purposes.