TY - JOUR
T1 - Adenine and adenosine salvage in Leishmania donovani
AU - Boitz, Jan M.
AU - Ullman, Buddy
N1 - Funding Information:
This work was supported by grant AI023682 provided by the National Institute of Allergy and Infectious Diseases .
PY - 2013
Y1 - 2013
N2 - 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.
AB - 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.
KW - Adenine aminohydrolase
KW - Adenine metabolism
KW - Adenine phosphoribosyltransferase
KW - Adenosine metabolism
KW - Leishmania donovani
KW - Purine salvage
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U2 - 10.1016/j.molbiopara.2013.06.005
DO - 10.1016/j.molbiopara.2013.06.005
M3 - Article
C2 - 23845934
AN - SCOPUS:84886939398
SN - 0166-6851
VL - 190
SP - 51
EP - 55
JO - Molecular and Biochemical Parasitology
JF - Molecular and Biochemical Parasitology
IS - 2
ER -