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, the Coccidians Toxoplasma gondii and Neospora caninum possess 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 and N. caninum 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 and N. caninum 2.7.7.3 enzymes (TGME49_030990 & NCLIV_031360) 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 and Neospora enzymes are mono functional.

 

Enzyme EC Number Gene id
Bifunctional 2-dehydropantoate 2-reductase/3-methyl-2-oxobutanoate hydroxymethyltransferase 1.1.1.169; 2.1.2.11 NCLIV_029910
Branched-chain-amino-acid-transaminase 2.6.1.42 NCLIV_006760
Branched-chain-amino-acid-transaminase 2.6.1.42 NCLIV_023450
Dephospho-CoA kinase 2.7.1.24 Missing in annotation
Pantothenate kinase 2.7.1.33 NCLIV_049910
Pantothenate kinase 2.7.1.33 NCLIV_060530
Pantetheine-phosphate adenylyltransferase 2.7.7.3 NCLIV_031360
Holo-[acyl-carrier-protein] synthase 2.7.8.7 NCLIV_021530
Holo-[acyl-carrier-protein] synthase 2.7.8.7 NCLIV_051620
Phosphopantothenoylcysteine decarboxylase 4.1.1.36 NCLIV_017870
Pantoate-beta-alanine ligase 6.3.2.1 NCLIV_039640
Phosphopantothenate-cysteine ligase 6.3.2.5 NCLIV_010940
Apo-[acyl-carrier protein] none NCLIV_023990
Apo-[acyl-carrier protein] none NCLIV_036350

 

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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