Comparison of tritiated hypoxanthine, adenine and adenosine for purine-salvage incorporation into nucleic acids of the malarial parasite, Plasmodium berghei.
This study was accomplished to examine the relative importance of different metabolic precursors of nucleic acid synthesis in the malarial parasite, P. berghei. Three possible pathways for incorporation of Adenine (type) compounds exist: 1) incorporation via hypoxanthine, 2) via adenine, or 3) via adenosine. The parasitized cell and erythrocyte-free malarial parasite were both examined because of possible metabolic differences that could be encountered. Hypoxanthine was clearly the best precursor at both levels with extra-incorporation in the presence of allopurinol (10(-4)M), which protects oxidative metabolism of hypoxanthine. Adenosine was less efficient in its incorporation into nucleic acids at both levels. Adenine was clearly the poorest precursor being extremely less efficient compared to hypoxanthine 1/50 at parasitized cell level and 1/100 at the free parasite level. At both levels adenine seemed to be slightly more efficient in the presence of allopurinol and this appeared to be a similar to the incorporation via adenosine with allopurinol. In both cases, part of the incorporation could be coming via conversion to hypoxanthine because allopurinol protects oxidation of hypoxanthine via inhibition of xanthine oxidase. With the prior observation of Manandhar and Van Dyke that adenosine is converted to hypoxanthine outside or on the surface of the malarial parasite one is lead to conclude that of the three pathways the hypoxanthine pathway is probably the major and possibly the almost totally important pathway making hypoxanthine's uptake and/or conversion to inosine monophosphate a key event of metabolic and chemotherapeutic importance.
D000225:Adenine / Q000378:metabolism; D000241:Adenosine / Q000378:metabolism; D000493:Allopurinol / Q000494:pharmacology; D000818:Animals; D004912:Erythrocytes / Q000469:parasitology; D007042:Hypoxanthines / Q000378:metabolism; D007288:Inosine / Q000378:metabolism; D007292:Inosine Nucleotides / Q000096:biosynthesis; D051379:Mice; D009696:Nucleic Acids / Q000096:biosynthesis*; D010962:Plasmodium berghei / Q000378:metabolism*; D011687:Purines / Q000378:metabolism*
D007042:Hypoxanthines; D007292:Inosine Nucleotides; D009696:Nucleic Acids; D011687:Purines; D007288:Inosine; D000493:Allopurinol; D000225:Adenine; D000241:Adenosine