Pantothenate and CoA biosynthesis

Coenzyme A (CoA) is an important cofactor (acyl-chain carrier) for many cellular functions including the citrate cycle and fatty acid biosynthesis and metabolism. Vitamin B5, also known as pantothenate is the precursor for CoA biosynthesis. Pantothenate synthesis takes place in plants, fungi and some bacteria, whereas animals salvage pantothenate from diet and CoA biosynthesis from pantothenate is present in most organisms. Plasmodium falciparum utilises pantothenate from host and converts it to CoA (CoA biosynthesis). In contrast, Toxoplasma gondii possesses the four enzymes required for the generation of pantothenate from the branched chain amino acid valine. Except dephospho-CoA kinase (2.7.1.24), all other enzymes involved in the downstream conversion of pantothenate to CoA are present. Dephospho-CoA kinase, an enzyme present in P. falciparum is missing in T. gondii gene models. It has previously been suggested that T. gondii pantothene-phosphate adenyl-transferase enzyme is similar to the mammalian bifunctional enzyme and possesses both pantothene-phosphate adenyl-transferase (2.7.7.3) and dephospho-CoA kinase activities, whereas P. falciparum and Cryptosporidium species have two separate enzymes [1]. The only known protein domain present in T. gondii 2.7.7.3 enzyme (TGME49_030990) is nucleotidyl-transferase, the same as in the P. falciparum enzyme, whereas mammalian enzyme possesses dephospho-CoA kinase domain as well. This suggests that Toxoplasma enzyme 2.7.7.3 is mono functional.

 

Protein EC Number Gene id Protein localisation Localisation data source
Bifunctional 2-dehydropantoate 2-reductase/3-methyl-2-oxobutanoate hydroxymethyltransferase 1.1.1.169; 2.1.2.11 TGME49_257050    
Branched-chain-amino-acid-transaminase 2.6.1.42 TGME49_281500    
Branched-chain-amino-acid-transaminase 2.6.1.42 TGME49_297850    
Dephospho-CoA kinase 2.7.1.24 Missing in annotation    
Pantothenate kinase 2.7.1.33 TGME49_235478    
Pantothenate kinase 2.7.1.33 TGME49_307770    
Pantetheine-phosphate adenylyltransferase 2.7.7.3 TGME49_230990    
Holo-[acyl-carrier-protein] synthase 2.7.8.7 TGME49_203420    
Holo-[acyl-carrier-protein] synthase 2.7.8.7 TGME49_214440 Nucleus Previous publication
Phosphopantothenoylcysteine decarboxylase 4.1.1.36 TGME49_242880    
Pantoate-beta-alanine ligase 6.3.2.1 TGME49_265870 Nucleus Previous publication
Phosphopantothenate-cysteine ligase 6.3.2.5 TGME49_318600    
Apo-[acyl-carrier protein] none TGME49_264080 Apicoplast Apiloc; Previous publication; Orthology transformation from P. falciparum
Apo-[acyl-carrier protein] none TGME49_270310    

 

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Sources and fates of metabolites

 

Substrate Source pathways Product Fate pathways
L-valine Host CoA Tricarboxylic acid (TCA) cycle
2-oxoglutarate Pyruvate metabolism, Tricarboxylic acid (TCA) cycle Glutamate Glutamate metabolism
Methylene-THF Folate biosynthesis THF Folate biosynthesis
beta-alanine Host    
Cysteine Glycine, serine and cysteine metabolism