FIGURE 1.

Extra- and intracellular adenosine production. Extracellularly, ATP can be dephosphorylated to AMP by ectonucleoside triphosphate diphospho-hydrolase (CD39) or ecto-nucleotide pyrophosphatase/phosphodiesterase. Then, AMP can be dephosphorylated to adenosine by the extracellular 5′-nucleotidase, CD73. Extracellular adenosine can be converted into hypoxanthine (Hyp) and ribose-1 phosphate (Rib-1-P) by the combined action of ectosolic adenosine deaminase and purine nucleoside phosphorylase. Extracellular Rib-1-P might be dephosphorylated by membrane phosphatases and equilibrates with the intracellular ribose through a not yet defined transporter (?). Inside the cell, at low energy charge, adenosine originates mainly from AMP and can be exported or deaminated. When extracellular adenosine generated from ATP breakdown is transported inside the cell, it might be phosphorylated by the low K_M ADK or deaminated by the high K_M ADA if adenosine reaches high levels. 1,3: ecto-nucleoside triphosphate diphosphohydrolase; 2: ecto-nucleotide pyrophosphatase/phosphodiesterase; 4: ecto-5′-nucleotidase; 5: adenosine deaminase; 6: purine nucleoside phosphorylase; 7: ribokinase; 8: phosphoribomutase; 9: 5-phosphoribosyl-1-pyrophosphate synthetase; 10: hypoxanthine guanine phosphoribosyltransferase; 11: adenosine kinase; 12: cytosolic 5′ nucleotidase I; 13: AMP deaminase; 14: cytosolic 5′ nucleotidase II; 15: S-adenosylhomocysteine hydrolase. Ado: adenosine; CNT: concentrative nucleoside transporter; ENT: equilibrative nucleoside transporter; Hyp: hypoxanthine; Ino: inosine; P1: purinergic receptor type 1; P2: purinerigic receptor type 2; Rib-1-P: ribose-1-phosphate; Rib-5-P: ribose-5-phosphate. Green and orange boxes indicate that these pathways are described in more details in Figures 2, 3. +: stimulation; -: inhibition.