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VOL. 73 (2), 537-566, 2007 ECTO-NUCLEOTIDASES, MOLECULAR PROPERTIES...

FIGURE 2. Membrane topology of ecto-nucleotidases and other nucleotide-
metabolizing enzymes. In contrast to NPP1 and NPP3 that are type 2 membrane
proteins, NPP2 is a secreted protein. Soluble adenosine deaminase (ADA) is bound

to the cell surface via the GPI-anchored protein CD26 (dipeptidyl peptidase IV).
CD38 and CD157 are NAD glycohydrolases (NADases). ARTs are ADP-

ribosyltransferases that (in part) also metabolize NAD+. Substrates and products
are given in Table 1. Not shown: Nucleoside diphosphate kinase and F1Fo

ATPsynthase/F1 ATPase. Extracellular ATP can also serve as a co-substrate for
ecto-protein kinases.

Extracellular NAD+ can be cleaved by E-NPPs but also by two
closely related families of extracellular NAD+ metabolizing enzymes,
NAD glycohydrolases (NADases) (CD38, CD157) and mono(ADP-
ribosyl)transferases (ARTs) (50) (Table 1). Ecto-5‘-nucleotidase, of
which only a single gene exists in the mammalian genome, hydroly-
ses only nucleoside monophosphates (51, 52). Additional surface-
located enzymes catalyze nucleotide interconversion and thus the
extracellular synthesis of nucleoside triphosphates and diphospha-
tes. These include ecto-nucleoside diphosphokinase and the adenine
nucleotide-specific ecto-ATP:AMP phosphotransferase (adenylate ki-
nase, myokinase) (53, 54) (Figure 2). Obviously, ecto-nucleotidases
are even more diverse than nucleotide receptors and we are only
beginning to understand their specific function in the context of the
modulation of ligand availability at nucleotide and nucleoside recep-
tors. Some of the principal properties of ecto-nucleotidases are brie-
fly summarized below.

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