Inborn errors in purine metabolism: role of 5'-nucleotidases and their involvement in the etiology of neurological impairments.

A number of scientists have been involved for decades in the study of nucleotide metabolism in different species of living beings. We are, therefore, aware of the relevant roles of purine compounds and of the many different ways in which these compounds influence cell life, acting both inside and outside the cells. Nevertheless, the consequences of an alteration (lack of expression, or hypo- or hyperexpression) in the activity of enzymes involved in the metabolism of these compounds are sometimes surprising, and far from being mechanistically explained. Alterations in enzyme activities involved in nucleotide metabolism are frequently associated with syndromes characterized by two different types of problems--one, metabolic, which is expected and can be easily explained, and the second, neurological and behavioral. Neurological and behavioral impairments are more difficult to explain and show a very high degree of individual variability. The molecular bases of the neurological impairment linked to purine metabolism disorders have been extensively studied. These studies have generated a lot of hypotheses but very few certainties. In this short review, neurological and behavioral symptoms linked to the dysfunction of some enzymes involved in purine synthesis, catabolism, and salvage will be briefly described, with particular attention to their metabolic and regulatory consequences. Finally, attention will be focused on the 5'-nucleotidase family members and on their involvement in the regulation of purine and pyrimidine metabolism.