Adenosine analog metabolism in Giardia lamblia. Implications for chemotherapy

Certain adenosine analogs can inhibit the growth of Giardia lamblia. This biological action correlates with the ability of the organism to phosphorylate the nucleoside directly to the nucleotide. Four of these, 8-azaadenosine, 1-deazaadenosine, 7-deazaadenosine, and 9-deazaadenosine, were very effective. The respective bases of the first three were ineffective. The base of 9-deazaadenosine was not tested as this C-nucleoside is non-cleavable. Metabolic studies using radioactive 7- and 9-deazaadenosine showed that these compounds were phosphorylated by the organism. Enzymatic assay confirmed the presence of nucleoside phosphotransferase activity; no nucleoside kinase activity was found. Preliminary characterization of this phosphotransferase suggests that it has different substrate and phosphate donor specificities than the mammalian enzyme and, therefore, may be a potential site for chemotherapeutic attack.