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Purine requirements for the expression of Cape buffalo serum trypanocidal activity
Institution:1. Department of Mechanical Engineering, Oakland University, Rochester, MI 48309, USA;2. Department of Mechanical Engineering, Texas Tech University, Lubbock, TX 79424, USA;1. School of Mechanical Engineering, The University of Adelaide, South Australia 5005, Australia;2. Institute for Combustion Technology, RWTH Aachen University, Aachen 52056, Germany;1. School of Energy and Power Engineering, Jiangsu University, Zhenjiang 212013, China;2. State Key Laboratory of Science and Technology on Ballistics, Nanjing University of Science and Technology, Nanjing, Jiangsu 210094, China;3. State Key Laboratory of Explosion Science and Technology, Beijing Institute of Technology, Beijing 100081, China
Abstract:Cape buffalo serum contains xanthine oxidase which generates trypanocidal H2O2 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 H2O2. 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.
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