Enzymes of purine and pyrimidine metabolism from the human malaria parasite, Plasmodium falciparum.
Plasmodium falciparum trophozoites were isolated by mechanical rupture of infected human erythrocytes followed by a series of differential centrifugation steps. After lysis with sonication, the 100 000 x g supernatant of parasites and uninfected host cells was used to determine the specific activities of a number of enzymes involved in purine and pyrimidine metabolism. P. falciparum possessed the purine salvage enzymes: adenosine deaminase, purine nucleoside phosphorylase, hypoxanthine-guanine phosphoribosyltransferase (PRTase), xanthine PRTase, adenine PRTase, adenosine kinase. The last two enzymes, however, were present at much lower activity levels. Hypoxanthine was converted (presumably via IMP) into adenine and guanine nucleotides only in the presence both of supernatant and membrane fractions of P. falciparum. Two enzymes involved in the de novo synthesis of pyrimidines, orotic acid PRTase, and orotidine 5'-phosphate decarboxylase, were present in parasite extracts as were the enzymes for pyrimidine nucleotide phosphorylation: UMP-CMP kinase, dTMP kinase, nucleoside diphosphate kinase. Xanthine oxidase, CTP synthetase, cytidine deaminase and several kinases for the salvage of pyrimidine nucleosides were not detected in the parasites. Both phosphoribosyl pyrophosphate synthetase and uracil PRTase were present but at low activity levels. Human erythrocytes displayed similar but not identical enzyme patterns. Enzyme specific activities, however, were generally much lower than those of the corresponding parasite enzymes.
D000243:Adenosine Deaminase / Q000378:metabolism; D000818:Animals; D004912:Erythrocytes / Q000201:enzymology; D006801:Humans; D007041:Hypoxanthine Phosphoribosyltransferase / Q000378:metabolism; D009703:Nucleoside-Phosphate Kinase / Q000378:metabolism; D009962:Orotate Phosphoribosyltransferase / Q000378:metabolism; D009964:Orotidine-5'-Phosphate Decarboxylase / Q000378:metabolism; D010430:Pentosyltransferases / Q000378:metabolism; D010963:Plasmodium falciparum / Q000201:enzymology*; D011683:Purine-Nucleoside Phosphorylase / Q000378:metabolism; D011687:Purines / Q000378:metabolism*; D011743:Pyrimidines / Q000378:metabolism*; D013937:Thymidine Kinase / Q000378:metabolism
D011687:Purines; D011743:Pyrimidines; D010430:Pentosyltransferases; D011683:Purine-Nucleoside Phosphorylase; D009962:Orotate Phosphoribosyltransferase; C024827:xanthine phosphoribosyltransferase; D007041:Hypoxanthine Phosphoribosyltransferase; D013937:Thymidine Kinase; D009703:Nucleoside-Phosphate Kinase; D000243:Adenosine Deaminase; D009964:Orotidine-5'-Phosphate Decarboxylase