Extracellular
nucleotides and
nucleosides act as signaling molecules involved in a wide spectrum of biological effects. Their levels are controlled by a complex cell surface-located group of
enzymes called ectonucleotidases. There are four major families of ectonucleotidases,
nucleoside triphosphate diphosphohydrolases (NTPDases/CD39), ectonucleotide
pyrophosphatase/
phosphodiesterases (E-
NPPs), alkaline
phosphatases and
ecto-5'-nucleotidase. In the last few years, substantial progress has been made toward the molecular identification of members of the ectonucleotidase families and their
enzyme structures and functions. In this review, there is an emphasis on the involvement of NTPDase and
5'-nucleotidase activities in disease processes in several tissues and cell types. Brief background information is given about the general characteristics of these
enzymes, followed by a discussion of their roles in thromboregulatory events in diabetes,
hypertension,
hypercholesterolemia and
cancer, as well as in pathological conditions where platelets are less responsive, such as in
chronic renal failure. In addition,
immunomodulation and cell-cell interactions involving these
enzymes are considered, as well as
ATP and
ADP hydrolysis under different clinical conditions related with alterations in the immune system, such as
acute lymphoblastic leukemia (ALL), B-
chronic lymphocytic leukemia (B-CLL) and
infections associated with human immunodeficiency virus (HIV). Finally, changes in
ATP,
ADP and
AMP hydrolysis induced by
inborn errors of metabolism,
seizures and
epilepsy are discussed in order to highlight the importance of these
enzymes in the control of neuronal activity in pathological conditions. Despite advances made toward understanding the molecular structure of ectonucleotidases, much more investigation will be necessary to entirely grasp their role in physiological and pathological conditions.