A multifunctional, ubiquitous molecule, adenosine acts at cell-surface G protein-coupled receptors, as well as numerous enzymes, including protein kinases and adenylyl cyclase. Extracellular adenosine is thought to be produced either by export or by metabolism, predominantly through ecto-5’-nucleotidase activity (also producing inorganic phosphate). It is inactivated either by extracellular metabolism via adenosine deaminase (also producing NH₃) or, following uptake by nucleoside transporters, via adenosine deaminase or adenosine kinase (requiring ATP as co-substrate). Intracellular adenosine may be produced by cytosolic 5’-nucleotidases or through S-adenosylhomocysteine hydrolase (also producing L-homocysteine).

With the exception of mitochondrial 5’-nucleotidase, each of the 5’-nucleotidases are localised to the cytoplasm.

An extracellular adenosine deaminase activity, termed ADA2 or adenosine deaminase growth factor (ADGF, CECR1, ENSG00000093072) has been identified [4], which is insensitive to EHNA [6]. Other forms of adenosine deaminase act on ribonucleic acids and may be divided into two families: ADAT1 (ENSG00000065457) deaminates transfer RNA; ADAR (EC 3.5.4.-, ENSG00000160710, also known as 136 kDa double-stranded RNA-binding protein, P136, K88DSRBP, Interferon-inducible protein 4); ADARB1 (EC 3.5.-.-, ENSG00000197381, also known as dsRNA adenosine deaminase) and ADARB2 (EC 3.5.-.- , ENSG00000185736, also known as dsRNA adenosine deaminase B2, RNA-dependent adenosine deaminase 3) act on double-stranded RNA. Particular polymorphisms of the ADA gene result in loss-of-function and severe combined immunodeficiency syndrome. Adenosine deaminase is able to complex with dipeptidyl peptidase IV (EC 3.4.14.5, ENSG00000197635, also known as T-cell activation antigen CD26, TP103, adenosine deaminase complexing protein 2) to form a cell-surface activity [3].

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4. Maier, SA; Galellis, JR; McDermid, HE. (2005) Phylogenetic analysis reveals a novel protein family closely related to adenosine deaminase. J. Mol. Evol., 61 (6): 776-94. [PMID:16245011]

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6. Zavialov, AV; Yu, X; Spillmann, D; Lauvau, G; Zavialov, AV. (2010) Structural basis for the growth factor activity of human adenosine deaminase ADA2. J. Biol. Chem., 285 (16): 12367-77. [PMID:20147294]