title: Adenosine is the primary precursor of all purine nucleotides in Trichomonas vaginalis.
abstract: Trichomonas vaginalis, a parasitic protozoan and the causative agent of trichomoniasis, lacks de novo purine nucleotide synthesis and possesses a unique purine salvage pathway, consisting of a bacterial type purine nucleoside phosphorylase and a purine nucleoside kinase. It is generally believed that adenine and guanine are converted to their corresponding nucleosides and then further phosphorylated to form AMP and GMP, respectively, as the main as well as the essential pathway of replenishing the purine nucleotide pool in the organism. Formycin A, an analogue of adenosine, inhibits both enzymes as well as the in vitro growth of T. vaginalis with an estimated IC(50) of 0.27 microM. This growth inhibition was reversed by adding adenine to the culture medium but not by adding guanine or hypoxanthine. Furthermore, T. vaginalis can grow in semi-defined medium supplemented with only adenine but not with guanine or hypoxanthine. Radiolabeling experiments followed by HPLC analysis of the purine nucleotide pool in T. vaginalis demonstrated incorporation of [8-14C]adenine into both adenine and guanine nucleotides, whereas [8-14C]guanine was incorporated only into guanine nucleotides. Substantial adenosine deaminase activity and significant IMP dehydrogenase and GMP synthetase activities were identified in T. vaginalis lysate, suggesting a pathway capable of converting adenine to GMP via adenosine. This purine salvage scheme depicts adenosine the primary precursor of the entire purine nucleotide pool in T. vaginalis and the purine nucleoside kinase one of the most pivotal enzymes in purine salvage and a potential target for anti-trichomoniasis chemotherapy.
authors.affiliation: Department of Pharmaceutical Chemistry, School of Pharmacy, University of California, 513 Parnassus Avenue, San Francisco, CA 94143-0446, USA.
authors.forename: Narsimha Rao
authors.initials: NR
authors.lastname: Munagala
authors.forename: Ching C
authors.initials: CC
authors.lastname: Wang
mesh_terms: D000241:Adenosine / Q000737:chemistry / Q000378:metabolism*; D000243:Adenosine Deaminase / Q000032:analysis; D000818:Animals; D002478:Cells, Cultured; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D005573:Formycins / Q000494:pharmacology; D011685:Purine Nucleotides / Q000032:analysis / Q000096:biosynthesis* / Q000737:chemistry*; D011687:Purines / Q000378:metabolism; D014246:Trichomonas vaginalis / Q000201:enzymology / Q000235:genetics / Q000254:growth & development / Q000378:metabolism*
chemical_list: D005573:Formycins; D011685:Purine Nucleotides; D011687:Purines; C034550:formycin; D000243:Adenosine Deaminase; D000241:Adenosine; C030985:purine