Murine Lymphocytes and Lymphocyte Cell Lines Secrete Adenosine Deaminase

Abstract

Adenosine deaminase (E.C. 3. 5. 4. 4, ADA), first enzyme in the degradative pathway of adenosine (Ado) and 2′-deoxyadenosine (dAdo), converts Ado to inosine (Ino) and dAdo to dIno. Purine nucleoside Phosphorylase (E.C. 2. 4. 2. 1, PNP), the second enzyme in the pathway converts Ino to hypoxanthine (HX). Cells from patients lacking ADA or PNP tend to accumulate dATP or dGTP respectively. The patients usually present with the clinical picture of acute immunodeficiency possibly due to a block in lymphocyte differentiation caused by the effects of the specific enzyme deficiency (1,2). It has been proposed that increased levels of purine deoxynucleoside triphosphates allosterically inhibit ribonucleotide reductase so that in dividing cells other deoxynucleotide levels are altered and ultimately DNA synthesis is impaired (3-5). Evidence has also been presented that accumulation of dATP may act at a point before the onset of DNA synthesis (6,7) and, indeed, dAdo Has been shown to induce strand breaks in the DNA of resting cells and to deplete cellular NAD and ATP.