TABLE 1.

Pathways and enzymes for extracellular metabolism of nucleotides and nucleosides

Extracellular Metabolic Function	Ectoenzyme Names/Subtypes	Catalytic Reaction	Substrate Selectivity	Inhibitors (Representative)	T-Cell Expression
Ecto-ATPase, Ecto-ADPase, Apyrase	CD39 family ENTDPase1–4	ATP > ADP (+Pi) > AMP (+Pi)	All purine and pyrimidine nucleotide tri/diphosphates	ARL-67156; others	Yes, but varies with differentiation and polarization state; high in Tregs
Ecto-ATP pyro-phosphatase/ phosphodisterase	ENPP1–3	ATP > AMP (+PPi)	Purine and pyrimidine nucleotide triphosphates	β,γ-methylene-ATP (competitive substrate)	Unknown but likely
Ecto-AMPase	CD73; ecto-5′-nucleotidase; (5Nte)	AMP > Ado (+Pi)	Purine and pyrimidine nucleotide monophosphates	α,β-methylene-ADP (APCP)	Yes, but varies with differentiation and polarization state; high in Tregs
Ecto-AMPase	Tissue nonselective TNAP	AMP > Ado (+Pi)	Purine and pyrimidine nucleotide monophosphates; non-nucleotide phosphate esters	Levamisole; tetramisole	Unknown
Ecto-AMPase, Ecto-Phosphatase	TM-PAP	AMP (and ATP) > Ado (+Pi)	Purine and pyrimidine nucleotide phosphates; non-nucleotide phosphate esters	l-Tartrate; some cyclic AMP analogs	Yes, but varies with differentiation and polarization state
Ecto-AMP Deaminase	AMPD3	AMP > IMP	AMP	Pentostatin/deoxycoformycin	Unknown
Ecto-Adenosine Deaminase	Ecto-ADA	Ado > Ino	AMP	Pentostatin/deoxycoformycin	Yes
Nucleoside transport (concentrative)	CNT (multiple subtypes)	Extracellular nucleoside > intracellular nucleoside	All natural nucleosides; many nucleoside analogs	Dipyridamole; many others	Yes
Nucleoside transport (equilibrative)	ENT (multiple subtypes)	Extracellular nucleoside > intracellular nucleoside	All natural nucleosides; many nucleoside analogs	Dipyridamole; many others	Yes

AMPD, AMP deaminase; CNT, concentrative nucleoside transporter; ENT, equilibrative nucleoside transport; Tregs, regulatory T cells.