Purine salvage in Schistosoma mansoni schistosomules

Abstract

Purine metabolism in developing Schistosoma mansoni schistosomules was investigated in erythrocyte-free and serum-free media to eliminate possible contamination from host metabolites or enzymes. The absence of de novo purine nucleotide synthesis in the parasite was confirmed by the lack of incorporation of radiolabeled glycine or formate into the nucleotide pool. Adenosine and adenine were equally incorporated into adenine nucleotides. The incorporation was not affected by hadacidin, an inhibitor of succinyl AMP synthetase. Adenosine and adenine therefore appear to be converted to AMP without forming IMP as an intermediate. Guanosine was first converted to guanine which was then incorporated into guanine nucleotides. There was no appreciable interconversion between adenine nucleotides and guanine nucleotides. Hypoxanthine was incorporated into all purine nucleotides, but most of it (90%) was found in the adenine nucleotides. The equilibrium however, was shifted by hadacidin in favor of guanine nucleotides; an indication that hypoxanthine was converted first to IMP and then to AMP or GMP. These findings, together with the previous observation that S. mansoni lacks functional purine nucleoside kinases lead to the conclusion that all purine nucleosides are primarily converted to the corresponding purine bases. The latter are then incorporated into the nucleotide pool via individual purine phosphoribosyl transferases. The three enzymic activities for salvaging adenine, guanine, and hypoxanthine thus constitute the major network for purine salvage in S. mansoni schistosomules.