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 TA03405
Ribonucleotide di-P reductase 1.17.4.1 TA05060
Ribonucleotide di-P reductase 1.17.4.1 TA06715
Ribonucleotide di-P reductase 1.17.4.1 TA09665
GMP reductase 1.7.1.7 TA21065
TRX reductase 1.8.1.9 TA04645
Purine nucleoside phosphorylase 2.4.2.1 TA13165
Purine nucleoside phosphorylase 2.4.2.1 TA13170
Purine nucleoside phosphorylase 2.4.2.1 TA13175
Adenosine kinase 2.7.1.20 Missing in annotation
Adenylate kinase 2.7.4.3 TA03055
Adenylate kinase 2.7.4.3 TA11865
Nucleoside diphosphate kinase 2.7.4.6 TA13095
Guanylate kinase 2.7.4.8 TA13945
3',5'-cyclic-nucleotide phosphodiesterase 3.1.4.17 TA02890
Adenosine deaminase 3.5.4.4 Missing in annotation
Inorganic diphosphatase 3.6.1.1 TA13735
Ecto-nucleoside triphosphate diphosphohydrolase 3.6.1.15 TA05355
Ecto-nucleoside triphosphate diphosphohydrolase 3.6.1.15 TA18135
Nucleoside-triphosphate pyrophosphatase 3.6.1.19 TA17785
Adenylosuccinate lyase 4.3.2.2 TA18170
Adenylate cyclase 4.6.1.1 TA03520
Guanylate cyclase 4.6.1.2 TA15475
Adenylosuccinate synthase 6.3.4.4 TA17235
GMP synthase 6.3.5.2 TA06065

 

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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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