Pyrimidine de novo Synthesis during the Life Cycle of the Intraerythrocytic Stage of Plasmodium falciparum

The 6 enzymes involved in de novo synthesis of pyrimidines were measured in Plasmodium falciparum isolated by saponin lysis from RBC's nonsynchronized and synchronized in vitro cultures. The total activities were found to be dependent on the stage of the P. falciparum cycle. In parasites isolat...

Full description

Saved in:
Bibliographic Details
Published in:The Journal of parasitology 1984-08, Vol.70 (4), p.536-541
Main Authors: Gero, Annette M., Brown, Graham V., O'Sullivan, William J.
Format: Article
Language:English
Subjects:
Adenosine Triphosphate - metabolism
Animals
Aspartate Carbamoyltransferase - metabolism
Biosynthesis
Carbamoyl-Phosphate Synthase (Glutamine-Hydrolyzing) - metabolism
Dihydroorotase - metabolism
Dihydroorotate Oxidase - metabolism
Electron Transport
Enzymes
Erythrocytes
Erythrocytes - parasitology
Kinetics
Orotate Phosphoribosyltransferase - metabolism
Orotidine-5'-Phosphate Decarboxylase - metabolism
Parasites
Parasitism
Phosphates
Plasmodium falciparum - enzymology
Plasmodium falciparum - growth & development
Plasmodium falciparum - metabolism
Pyrimidines
Saponins
Sulfonic acids
Therapy
Trophozoites
Uracil Nucleotides - biosynthesis
Uridine Monophosphate - biosynthesis
Citations: Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:The 6 enzymes involved in de novo synthesis of pyrimidines were measured in Plasmodium falciparum isolated by saponin lysis from RBC's nonsynchronized and synchronized in vitro cultures. The total activities were found to be dependent on the stage of the P. falciparum cycle. In parasites isolated from synchronized cultures, the highest activities for all enzymes were found at about 27 hr after synchronization in the late trophozoite stage, or just before schizont formation. Merozoites and ring forms contained little de novo activity. The first enzyme of the pathway, carbamyl phosphate synthetase (CPS-II) preferentially utilized glutamine. Ammonia was a poor substrate. CPS-II was unstable in the absence of the cryoprotectants, dimethyl-sulfoxide and glycerol. The apparent Km for MgATP-- was 3.8 ± 0.7 mM and the enzyme in all morphological forms of P. falciparum (ring, mature trophozoites and schizonts) was inhibited by UTP. The activity of the fourth enzyme of the pathway, dihydroorotate dehydrogenase, appeared to be linked to the cell's respiratory chain; inhibitors of mammalian electron transport such as cyanide, amytal, antimycin A, thenoyltrifluoroacetone and ubiquinone analogs also inhibited the P. falciparum enzyme. The demonstration of the variation of activity of the pyrimidine enzymes correlates with the increased synthesis of nucleic acids in the late trophozoite stage. These observations provide a basis for the testing of the effectiveness of pyrimidine analogs as potential anti-metabolites against various forms of the parasite.
ISSN:0022-3395
1937-2345
DOI:10.2307/3281402