Nucleosides and Lymphocytes–An Overview

Abstract

Overview. In recent years nucleoside biochemistry and lymphocyte physiology have been brought together in a number of ways. Lymphocytes are particularly sensitive to the cytotoxic effects of low concentrations of nucleosides. Deficiencies in certain enzymes of nucleoside metabolism result in immune dysfunction. In addition, lymphocyte proliferation and differentiation can be stimulated by other nucleosides and numerous observations have been made of variations in the activities of the enzymes involved in nucleoside metabolism as they relate to different stages of lymphocyte activation or function. Naturally occurring purine and pyrimidine nucleosides participate in intermediary metabolism. Furthermore, many nucleoside analogs and derivatives have been synthesized, some of which have significant biological effects and serve as anticancer agents for lymphoid malignancies. The interface between different nucleosides and their effects on lymphocyte function is the topic of this issue.

Nucleosides and their phosphorylated derivatives participate in the general metabolism of lymphocytes as they do in all cells in a wide variety of biochemical reactions. ATP is the universal energy currency and adenine nucleotides are components of the major coenzymes FAD, NAD, and coenzyme A. Also, nucleotides are the building blocks for nucleic acids, both RNA and DNA. Nucleotides serve as activated intermediates in many biosynthetic reactions. Finally, nucleotides are regulator molecules for enzymes involved in their own metabolism: ribonucleotide reductase is activated or inactivated depending on the concentrations of several different nucleotides; adenylate cyclase is regulated by GTP which binds to modulatory proteins [for effects on lymphoid cells see Ref (1) and P. Insel, this issue].

Besides their overall importance in metabolism, nucleosides are highly cytotoxic, particularly for lymphocytes. Indeed, various diseases of the immune system have been correlated with a lack or reduced amounts of enzymes involved in nucleoside metabolism.