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. 2022 Mar 8;12(3):418. doi: 10.3390/biom12030418

Figure 1.

Figure 1

Adenosine metabolism. The canonical pathway of adenosine synthesis involves the hydrolysis of ATP to AMP by ecto-nucleoside triphosphate diphosphohydrolase (NTPDase1, CD39) and the hydrolysis of AMP by ecto-5′-nucleotidase (5′NT, CD73). The non-canonical pathway involves the use of NAD+ as a substrate by CD38 or CD157 to generate ADP-ribose (ADPR) directly or through its cyclic form (cADPR). ADPR is then processed to AMP by CD203a (Ectonucleotide Pyrophosphatase/Phosphodiesterase 1). Extracellular adenosine can bind to its receptors or be metabolized to inosine by ecto-adenosine deaminase (ecto-ADA). Adenosine is transported into and out of the cell by concentrative or equilibrative nucleoside transporters (NTs). Intracellular adenosine synthesis is controlled by the balance of the activity of enzymes: adenosine kinase (ADK), cytoplasmic 5′nucleotidase (Cyto-5′NT), adenosine deaminase (ADA). Adenosine is generated as an end product in the transmethylation reaction: transmethylation reactions include the transfer of methyl groups from S-adenosylmethionine (SAM) to a wide range of acceptors. The resulting product, S-adenosylhomocysteine (SAH), is then cleaved by SAH hydrolase (SAHH) into adenosine and homocysteine.