Pyrimidine metabolism (biosynthesis)

The apicomplexans Toxoplasma gondii and Plasmodium falciparum can synthesise pyrimidine de novo from aspartate and glutamine. The Cryptosporidium species cannot synthesise pyrimidines de novo and salvages it from host. T. gondii also possess the salvage mechanisms in addition to de novo synthesis, whereas P. falciparum does not possess salvaging ability. The Piroplasma species possess the capability to synthesise pyrimidines de novo and cannot salvage pyrimidines from host. This suggests that they are similar to Plasmodium species when compared to the Coccidia. The presence of five of six enzymes of UMP biosynthesis pathway was shown to be conclusively present in Babesia rodhaini from the measurement of their specific activities [1]. The activities of all the six enzymes had been demonstrated in Babesia bovis and Babesia bigemina by Gero et al. The specific activities of the Babesia enzymes were of the same order of magnitude to the enzymes of the rodent malaria parasite Plasmodium berghei [2].

 

The genes for these six enzymes of de novo biosynthesis are present in the genomes of both Theileria species and B. bovis. The enzyme CTP synthase is present in all apicomplexans including Piroplasma species and is the only enzyme involved in the conversion of uridine to cytidine nucleotides. In addition to these, the enzyme cytidine/dCTP deaminase, an enzyme involved in deamination of dCTP to dUTP is present in Plasmodium, Toxoplasma and Piroplasma species. Other salvage enzymes present in T. gondii and absent in P. falciparum such as dCMP deaminase, uracil phosphoribosyltransferase (UPRT) and pyrimidine (uridine) phosphorylase are absent in these species.

 

Enzyme EC Number Gene id
Ribonucleotide di-P reductase 1.17.4.1 BBOV_I004870
Ribonucleotide di-P reductase 1.17.4.1 BBOV_IV006460
Ribonucleotide di-P reductase 1.17.4.1 BBOV_IV010610
Dihydroorotate dehydrogenase 1.3.5.2 BBOV_II007190
TRX reductase 1.8.1.9 BBOV_I002190
Thymidylate synthetase 2.1.1.45 BBOV_II000780
Aspartate carbamoyltransferase 2.1.3.2 BBOV_I003660
Orotate phosphoribosyl transferase 2.4.2.10 BBOV_IV000530
Cytidylate kinase 2.7.4.14 BBOV_II007680
Nucleoside-diphosphate kinase 2.7.4.6 BBOV_III005290
dTMP kinase 2.7.4.9 BBOV_III006440
UTP-glucose-1-P uridylyltransferase 2.7.7.9 BBOV_I003580
Dihydroorotase 3.5.2.3 BBOV_III009670
Cytidine deaminase/dCTP deaminase 3.5.4.5; 3.5.4.13 BBOV_III000450
Nucleoside-triphosphate pyrophosphatase 3.6.1.19 BBOV_III001450
dUTP diphosphatase 3.6.1.23 BBOV_IV005770
Orotidine-5'-phosphate decarboxylase 4.1.1.23 BBOV_IV011760
Carbonic anhydrase 4.2.1.1 BBOV_III005360
CTP synthase 6.3.4.2 BBOV_II005340
Carbamoyl-P synthase 6.3.5.5 BBOV_III003590

 

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Sources and fates of metabolites

 

Substrate Source pathways Product Fate pathways
Glutamine Host Glutamate Glutamate metabolism
Aspartate Glutamate metabolism UTP/CTP Transcription, Many metabolic pathways
PRPP Pentose phosphate cycle dTTP/dCTP DNA replication
Methylene-THF Recycling of folate DHF Recycling of folate