5′-Methylthioadenosine (MTA) Phosphorylase from Promastigotes of Leishmania Donovani

Abstract

The activity of various purine analogues against the pathogenic protozoan Leishmania donovani together with the lack of de novo synthesis in Leishmania (sp) has led to more detailed investigations into the purine metabolism of this organism (1, 2, 3, 4). These studies have shown that marked differences in purine metabolism exist between the host and parasite. In a previous report, the naturally occurring purine ribo-nucleosides and 2′-deoxyribonucleosides had been shown to be cleaved in promastigote extracts of L. donovani (5). A detailed investigation revealed the existence of high levels of catabolic enzymes that cleave purine nucleosides in extracts of the promastigote form of this organism. That work also characterized three distinct nucleoside hydrolases. One hydrolyzed purine and pyrimidine ribonucleosides, another cleaved only purine ribonucleosides, while the third hydrolyzed only purine 2′-deoxy-ribonucleosides. None of these enzymes cleaved adenosine and only the purine 2′-deoxyribonucleosidase hydrolyzed 2′-deoxyadenosine. Adenosine was a potent inhibitor of the purine ribonucleosidase (K_is = 5 μM), but had little effect on the other two enzymes. In addition, that study identified an adenosine-cleaving activity in crude extracts (5). This report describes further studies on that adenosine-cleaving activity from the promastigote form of Leishmania donovani.