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

diphosphates. NPP1 is a major source of extracellular PPi which is

highly relevant in the control of bone mineralization (44). Hydrolysis

of dinucleoside polyphosphates (ApnAs) by NPPs is asymmetric and
involves the a, ß-pyrophosphate bond, resulting in the production
of AMP and Apn-1 (71). Thus, hydrolysis of Ap5A, Ap4A, or Ap3A yields
adenosine tetraphosphate, ATP and ADP, respectively (72). This could

in turn lead to the additional or also continued activation of P2
receptors, depending on available receptor subtype. NAD+ is

hydrolyzed by NPPs to AMP and nicotinamide mononucleotide.

Alkaline phosphatases

The four human isoforms of alkaline phosphatases (kidney/bone/
liver [= tissue non-specific form, TNAP], placental, intestinal and
germ-cell are dimers, share a glycosylphosphatidyl inositol (GPI)
anchor and can give rise to soluble forms. The distribution of
isoforms varies to some extent between humans and rodents (45,
46). Alkaline phosphatases are non-specific phosphomonoesterases
that degrade nucleoside 5’-tri-, -di-, and -monophosphates, hydrolyze
inorganic pyrophosphate (PPi) and also release inorganic phosphate
from a large variety of organic compounds, including proteins. Thus,
alkaline phosphatases are capable of directly producing the P1
receptor agonist adenosine from extracellular ATP. Their pH
optimum is in the high alkaline range but they hydrolyze ATP also
at a pH of 7.4. Alkaline phosphatases certainly play an important
role in purine salvage but they can also modulate purinergic
signaling. The crystal structures of bacterial, shrimp and human
enzymes have been resolved (45, 75).

NUCLEOTIDE SYNTHESIS AND INTERCONVERSION

Ecto-nucleoside diphosphate kinase interconverts nucleoside
5’-di- and -triphosphates, leading to the formation of e.g. UTP and
ADP from ATP and UDP or of ATP and UDP from UTP and ADP.
This can result in the mutual activation or inactivation of receptors
for ATP, ADP, UTP and UDP. Together with other ecto-nucleotidases,
ecto-nucleoside diphosphate kinase may maintain low steady state

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