Purine metabolism (salvage)

The purine nucleotides are not only required as components of nucleic acids, but also as cofactors of metabolic processes and as a source of energy (ATP). Apicomplexa cannot synthesise purine rings de novo and salvage them from host. The putative transporters involved in the uptake of purine bases and nucleosides from parasitophorous vacuole are present in apicomplexans including Toxoplasma gondii, Plasmodium falciparum and Cryptosporidium parvum.

 

Piroplasma species possess limited set of enzymes involved in the salvage and inter-conversions of purines. The main purine salvaged by Babesia species is adenosine and the activities of some of the enzymes catalysing inter-conversions to AMP and GMP are detected in very early studies of Babesia divergens [1]. Matias et al also demonstrated the capability of synthesising adenosine and hypoxanthine into AMP and GMP in Babesia bovis [2] although the enzyme hypoxanthine-xanthine-guanine phosphoribosyltransferase (HXGPRT) is absent in the genomes of these species. The enzymes required for the conversion of adenosine to AMP and IMP such as adenosine deaminase and adenosine kinase are present in B. bovis genome, but missing in the gene models of Theileria parva and Theileria annulata. The enzymes catalysing the conversion of IMP to GMP and AMP are present in all Piroplasma species.

 

The toxicities of adenosine or deoxyadenosine analogues were tested in vitro against B. bovis. The comparison of the toxicity results to mammalian cell lines showed that many compounds relatively non-toxic towards mammalian cells are toxic towards Babesia. This shows the significant variation between transport, metabolism and incorporation into nucleic acids between Babesia and mammals [3]. This may also suggest the dependence of Babesia on adenosine alone as a source of purine rings and the potential of it as a drug target.

 

Enzyme EC Number Gene id
IMP dehydrogenase 1.1.1.205 TP03_0220
Ribonucleotide di-P reductase 1.17.4.1 TP01_0725
Ribonucleotide di-P reductase 1.17.4.1 TP01_1196
Ribonucleotide di-P reductase 1.17.4.1 TP03_0528
GMP reductase 1.7.1.7 TP01_0363
TRX reductase 1.8.1.9 TP03_0110
Purine nucleoside phosphorylase 2.4.2.1 TP02_0437
Purine nucleoside phosphorylase 2.4.2.1 TP02_0438
Purine nucleoside phosphorylase 2.4.2.1 TP02_0439
Purine nucleoside phosphorylase 2.4.2.1 TP02_0440
Adenosine kinase 2.7.1.20 Missing in annotation
Adenylate kinase 2.7.4.3 TP01_0633
Adenylate kinase 2.7.4.3 TP02_0203
Nucleoside-diphosphate kinase 2.7.4.6 TP02_0422
Guanylate kinase 2.7.4.8 TP02_0576
3',5'-cyclic-nucleotide phosphodiesterase 3.1.4.17 TP01_0664
3',5'-cyclic-nucleotide phosphodiesterase 3.1.4.17 TP01_1200
Adenosine deaminase 3.5.4.4 Missing in annotation
Inorganic diphosphatase 3.6.1.1 TP02_0061
Ecto-nucleoside triphosphate diphosphohydrolase 3.6.1.15 TP03_0144
Ecto-nucleoside triphosphate diphosphohydrolase 3.6.1.15 TP03_0766
Nucleoside-triphosphate pyrophosphatase 3.6.1.19 TP03_0695
Adenylosuccinate lyase 4.3.2.2 TP03_0773
Adenylate cyclase 4.6.1.1 TP03_0241
Guanylate cyclase 4.6.1.2 TP02_0848
Adenylosuccinate synthase 6.3.4.4 TP04_0033
GMP synthase 6.3.5.2 TP01_0862

 

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Sources and fates of metabolites

 

Substrate Source pathways Product Fate pathways
Adenosine Host dATP/dGTP DNA replication
    ATP/GTP Transcription, Many metabolic pathways
Glutamine Host Glutamate Glutamate metabolism
Aspartate Glutamate metabolism Fumarate Tricarboxylic acid (TCA) cycle


 

Nucleoside catabolism

 

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