Recycling of folate

Folic acid, also known as Vitamin B9 is important to several biological functions. The folate derivative, 5,10-methylene-tetrahydrofolate is essential for the synthesis of dTMP from dUMP and it is therefore crucial for DNA replication and cell division. Tetrahydrofolate is an essential substrate in the biosynthesis of amino acid, glycine. The de novo folate biosynthesis pathway is present in both Plasmodium falciparum and Toxoplasma gondii and the drugs targeting folate biosynthesis pathway has long been prescribed as anti-malarial agents. The enzymes for the biosynthesis of folate are absent in the genomes of Cryptosporidium and Piroplasma species. Thymidylate cycle, a part of folate pathway is present in Piroplasma species. This plays important role in the generation of amino acid glycine and dTMP. Dihydrofolate reductase enzyme replenishes tetrahydrofolate from dihydrofolate for the above mentioned biosynthetic processes. The dihydrofolate reductase and thymidylate synthase activities are catalysed by a bifunctional enzyme in Apicomplexa. The bifunctional enzyme tetrahydrofolylpolyglutamate synthase – dihydrofolate synthase is present in Theileria and absent in Babesia bovis. This suggests that Theileria can salvage dihydropteroate and convert it to folate, whereas B. bovis can salvage folate only. The inhibition of growth of B. bovis with folate analogues and no effect with inhibitors of folate biosynthesis pathways suggest the absence of de novo folate synthesis and the importance of dihydrofolate reductase activity in B. bovis [1].

 

Enzyme EC Number Gene id
Bifunctional dihydrofolate reductase/ thymidylate synthase 1.5.1.3; 2.1.1.45 TA08775
Serine hydroxymethyltransferase 2.1.2.1 TA20940
Bifunctional tetrahydrofolylpolyglutamate synthase/dihydrofolate synthase 6.3.2.12; 6.3.2.17 TA20775
Folate/biopterin (BT1 family) transporter none TA04055
Folate/biopterin (BT1 family) transporter none TA04060
Folate/biopterin (BT1 family) transporter none TA04370

 

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Sources and fates of metabolites

 

Substrate Source pathways Product Fate pathways
Dihydrofolate Host    
Serine Host Glycine Glycine and serine metabolism