Pyridoxal phosphate (Vitamin B6) salvage

Pyridoxal 5’-phosphate (PLP) is the active form of vitamin B6, whereas pyridoxamine, pyridoxal and pyridoxine and their phosphate esters form the vitamin B6 complex. PLP is a cofactor crucial for the functioning of many enzymes involved in amino acid metabolism. There are two different routes of de novo PLP synthesis present in different organisms. In the DOXP-dependent first route, the PLP precursor pyridoxine 5’-phosphate (PNP) is produced from 4-phosphohydroxyl-L-threonine (4PHT) and 1-deoxy-D-xylulose-5-phosphate (DOXP) by the actions of the enzymes PdxA and PdxJ. These precursors are synthesised from two independent pathways from metabolites of carbohydrate metabolism. PNP can then be converted to PLP by the enzyme pyridoxal 5’-phosphate synthase (pyridoxamine/pyridoxine 5’-phosphate oxidase). In the DOXP-independent second route, PLP synthesis is catalysed by the actions of Pdx1 and Pdx2 with glutamine, ribulose 5-phosphate (or ribose 5-phosphate) and glyceraldehyde 3-phosphate (or glycerone phosphate) as substrates [1]. PLP is de novo synthesised in the apicomplexans Plasmodium falciparum and Toxoplasma gondii through the DOXP-independent second route. These biosynthesis enzymes and the enzymes of the DOXP-dependent route are absent in the Cryptosporidium species suggesting the absence of biosynthetic capability.

 

The pyridoxine, pyridoxamine and pyridoxal can be phosphorylated with the action of the enzyme pyridoxal kinase (PdxK) and the first two can be converted to the later by the action of pyridoxal 5’-phosphate synthase. The genes for these two enzymes are present in Cryptosporidium muris as in P. falciparum and T. gondii. Although these enzymes are absent in Cryptosporidium parvum and Cryptosporidium hominis, PLP dependent enzymes are present in all three Cryptosporidium species. The presence of these two enzymes in C. muris suggests that they can salvage pyridoxal, pyridoxamine and pyridoxine and can interconvert them to the active PLP.

 

Enzyme EC Number Gene id
Pyridoxal 5'-phosphate synthase 1.4.3.5 CMU_007920
Pyridoxal kinase 2.7.1.35 CMU_036230

 

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Pyridoxal phosphate dependent enzymes in C. muris genome

 

Enzyme EC Number Gene id
Serine hydroxymethyltransferase 2.1.2.1 CMU_026590
Serine hydroxymethyltransferase 2.1.2.1 CMU_026630
Serine C-palmitoyltransferase 2.3.1.50 CMU_016830
Bifunctional adenosylmethionine-8-amino-7-oxononanoate transaminase/dethiobiotin synthase 2.6.1.62; 6.3.3.3 CMU_028160
Cysteine desulfurase 2.8.1.7 CMU_018170
Cysteine desulfurase 2.8.1.7 CMU_042710
Phosphatidylserine decarboxylase 4.1.1.65 CMU_001440
Alanine racemase 5.1.1.1 CMU_041300