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Cell death by apoptosis and necrosis releases ATP into the extracellular space. Adenosine is then generated from cleavage of ATP and ADP into AMP by the surface enzyme ecto-nucleoside-triphosphate-disphosphohydrolase1 (E-NTPDase1 or CD39) highly expressed in the kidneys. AMP is then dephosphorylated to adenosine by ecto-5′-nucleotidase (CD73). Phosphohydrolysis of AMP by CD73 is the rate-limiting step in this pathway.
