Page 90 - 73_02

HERBERT ZIMMERMANN Y COLS. AN. R. ACAD. NAC. FARM.

concentrations of nucleoside triphosphates at the cell surface, leading
to tonic receptor activation. Ecto-ATP:AMP phosphotransferase
(adenylate kinase, myokinase) catalyzes the extracellular formation
of ATP and AMP from ADP and vice versa (53, 54, 76).

ECTO-5’-NUCLEOTIDASE

The GPI-anchored ecto-5’-nucleotidase (CD73) is a Zn2+-binding
dimeric protein that hydrolyzes nucleoside monophosphates to their
respective nucleosides. It differs from intracellular 5’-nucleotidases
(52). The crystal structure of the periplasmic 5’-nucleotidase from
Escherichia coli (77) serves as a model for the structural analysis
of the related mammalian enzyme (78). Like alkaline phosphatase,
ecto-5’-nuceotidase can catalyze the formation of adenosine from
extracellular AMP and the concomitant activation of P1 adenosine
receptors. ATP and ADP inhibit AMP hydrolysis, resulting in feed
forward inhibition of ecto-5’-nucleotidase (79). The enzyme is broadly
distributed within various tissues and associated also with the
vascular endothelium but apparently with an expression pattern
different from alkaline phosphatase (TNAP) (80).

CD38 AND RELATED PROTEINS

NAD glycohydrolases (NADases) (CD38, CD157) and ADP-
ribosyltransferases (ARTs) represent two closely related families of
extracellular NAD+ metabolizing enzymes that cleave NAD+ at the
adenosine diphosphoribosyl-nicotinamide linkage. NADases convert
NAD+ to ADP-ribose and nicotinamide and due to their additional
ADP-ribosyl cyclase activity also to cyclic ADP-ribose. ARTs also
transfer ADP ribose to acceptor proteins, including the P2X7 receptor
(81, 82). The extracellularly formed cyclic ADP-ribose is considered
to be transported into the cell where it activates Ca2+ release from
intracellular stores (50).

548