title: Purine salvage networks in Giardia lamblia.
abstract: Purine metabolism in Giardia lamblia was investigated by monitoring incorporation of radiolabeled precursors into purine nucleotides in the log-phase trophozoites cultivated in vitro in axenic media and incubated in buffered saline glucose. The lack of incorporation of formate, glycine, hypoxanthine, inosine, and xanthine into the nucleotide pool suggests the absence of de novo purine nucleotide synthesis and the inability to form IMP as the precursor of AMP and GMP in G. lamblia. Only adenine, adenosine, guanine, and guanosine were incorporated. Further analysis of the labeled nucleotides by HPLC indicated that adenine and adenosine are converted only to adenine nucleotides whereas guanine and guanosine are only incorporated into guanine nucleotides. There is no competition of incorporation between adenine/adenosine and guanine/guanosine, and there is no interconversion between adenine and guanine nucleotides. Results from analyzing [5'-3H]guanosine incorporation indicate that the ribose moiety is not incorporated with the guanine base. Assays of purine salvage enzymic activities in the crude extracts of G. lamblia revealed the presence of only four major enzymes; adenosine and guanosine hydrolases and adenine and guanine phosphoribosyl transferases. Apparently, G. lamblia has an exceedingly simple purine salvage system; it converts adenosine and guanosine to corresponding purine bases and then forms AMP and GMP by the actions of corresponding purine phosphoribosyl transferases. The guanine phosphoribosyl transferase in G. lamblia is interesting because it does not recognize either hypoxanthine or xanthine as substrate. It thus must have a unique substrate specificity and may be regarded as a potential target to attack as a rational approach to chemotherapeutic control of giardiasis.
mesh_terms: D000227:Adenine Nucleotides / Q000378:metabolism; D000818:Animals; D005872:Giardia / Q000378:metabolism*; D006150:Guanine Nucleotides / Q000378:metabolism; D007291:Inosine Monophosphate / Q000378:metabolism; D009699:N-Glycosyl Hydrolases / Q000378:metabolism; D010430:Pentosyltransferases / Q000378:metabolism; D011685:Purine Nucleotides / Q000378:metabolism*; D011687:Purines / Q000378:metabolism*; D014246:Trichomonas vaginalis / Q000378:metabolism; D014318:Tritrichomonas / Q000378:metabolism
chemical_list: D000227:Adenine Nucleotides; D006150:Guanine Nucleotides; D011685:Purine Nucleotides; D011687:Purines; D007291:Inosine Monophosphate; D010430:Pentosyltransferases; C022484:purine phosphoribosyltransferase; D009699:N-Glycosyl Hydrolases; C030681:purine nucleosidase; C019599:adenosine nucleosidase