Enzymes of uridine 5'-monophosphate biosynthesis in Schistosoma mansoni.
In Schistosoma mansoni, the major product of in vitro orotate metabolism was orotidine 5'-monophosphate (OMP), whereas in mouse liver it was UMP. In contrast to mammalian cells, OMP appeared not to be 'channeled' from orotate phosphoribosyltransferase to OMP decarboxylase in S. mansoni, resulting in substantial degradation of OMP to orotidine. Significant differences were observed in the inhibitor specificity of phosphoribosyltransferase between S. mansoni and mouse liver, indicating that this enzyme may be a potential chemotherapeutic target in S. mansoni. Two distinct phosphoribosyltransferases were found in S. mansoni. One enzyme, having the higher molecular weight, utilized orotate, 5-fluorouracil and uracil as substrates, while the other only orotate. Both enzymes were inhibited by 5-azaorotic acid (oxonic acid) but only the 'orotate-specific' enzyme was inhibited by 4,6-dihydroxypyrimidine. OMP decarboxylase activity co-eluted with both phosphoribosyltransferases from Sephadex G-100 gel chromatography. We suggest that phosphoribosyltransferase in S. mansoni plays a role in both de novo UMP biosynthesis as well as in the salvage of uracil and uridine.
D015720:5'-Nucleotidase; D000818:Animals; D002250:Carbon Radioisotopes; D007700:Kinetics; D008099:Liver / Q000201:enzymology; D051379:Mice; D009708:Nucleotidases / Q000378:metabolism; D009962:Orotate Phosphoribosyltransferase / Q000378:metabolism; D009964:Orotidine-5'-Phosphate Decarboxylase / Q000378:metabolism; D010430:Pentosyltransferases / Q000378:metabolism*; D012550:Schistosoma mansoni / Q000201:enzymology*; D014500:Uracil Nucleotides / Q000096:biosynthesis*; D014542:Uridine Monophosphate / Q000096:biosynthesis*
D002250:Carbon Radioisotopes; D014500:Uracil Nucleotides; D014542:Uridine Monophosphate; D010430:Pentosyltransferases; D009962:Orotate Phosphoribosyltransferase; D009708:Nucleotidases; D015720:5'-Nucleotidase; D009964:Orotidine-5'-Phosphate Decarboxylase