6-aminopurine metabolism in Leishmania is unique among trypanosomatid pathogens since this genus expresses two distinct routes for adenine salvage: adenine phosphoribosyltransferase (APRT) and adenine deaminase (AAH). To evaluate the relative contributions of APRT and AAH, adenine salvage was evaluated in Δaprt, Δaah, and Δaprt/Δaah null mutants of L. donovani. The data confirm that AAH plays the dominant role in adenine metabolism in L. donovani, although either enzyme alone is sufficient for salvage. Adenosine salvage was also evaluated in a cohort of null mutants. Adenosine is also primarily converted to hypoxanthine, either intracellularly or extracellularly, but can also be phosphorylated to the nucleotide level by adenosine kinase when the predominant pathways are genetically or pharmacologically blocked. These data provide genetic verification for the relative contributions of 6-aminopurine metabolizing pathways in L. donovani and demonstrate that all of the pathways can function under appropriate conditions of genetic or pharmacologic perturbation.
Keywords: 2′-deoxycoformycin; AAH; ADA; ADSS; AK; APRT; Adenine aminohydrolase; Adenine metabolism; Adenine phosphoribosyltransferase; Adenosine metabolism; EHNA; HGPRT; Leishmania donovani; Purine salvage; XPRT; adenine aminohydrolase; adenine phosphoribosyltransferase; adenosine deaminase; adenosine kinase; adenylosuccinate synthetase; dCF; erythro-9-(2-hydroxy-3-nonyl)adenine; hypoxanthine-guanine phosphoribosyltransferase; xanthine phosphoribosyltransferase.
Published by Elsevier B.V.