Purine requirements for the expression of Cape buffalo serum trypanocidal activity.
Cape buffalo serum contains xanthine oxidase which generates trypanocidal H(2)O(2) during the catabolism of hypoxanthine and xanthine. The present studies show that xanthine oxidase-dependent trypanocidal activity in Cape buffalo serum was also elicited by purine nucleotides, nucleosides, and bases even though xanthine oxidase did not catabolize those purines. The paradox was explained in part, by the presence in serum of purine nucleoside phosphorylase and adenosine deaminase, that, together with xanthine oxidase, catabolized adenosine, inosine, hypoxanthine, and xanthine to uric acid yielding trypanocidal H(2)O(2). In addition, purine catabolism by trypanosomes provided substrates for serum xanthine oxidase and was implicated in the triggering of xanthine oxidase-dependent trypanocidal activity by purines that were not directly catabolized to uric acid in Cape buffalo serum, namely guanosine, guanine, adenine monophosphate, guanosine diphosphate, adenosine 3':5-cyclic monophosphate, and 1-methylinosine. The concentrations of guanosine and guanine that elicited xanthine oxidase-dependent trypanocidal activity were 30-270-fold lower than those of other purines requiring trypanosome-processing which suggests differential processing by the parasites.
Wang
Q
Q
Department of Veterinary and Animal Sciences, University of Massachusetts, Amherst, MA 01003, USA.
Hamilton
E
E
Black
S J
SJ
D000818:Animals; D002020:Buffaloes / Q000097:blood*; D002851:Chromatography, High Pressure Liquid; D006861:Hydrogen Peroxide / Q000097:blood; D016877:Oxidants / Q000378:metabolism; D011683:Purine-Nucleoside Phosphorylase / Q000378:metabolism; D011687:Purines / Q000378:metabolism*; D013379:Substrate Specificity; D014344:Trypanocidal Agents / Q000097:blood*; D014346:Trypanosoma brucei brucei / Q000187:drug effects / Q000254:growth & development; D014969:Xanthine Oxidase / Q000097:blood*
D016877:Oxidants; D011687:Purines; D014344:Trypanocidal Agents; D006861:Hydrogen Peroxide; D014969:Xanthine Oxidase; D011683:Purine-Nucleoside Phosphorylase