Pyridoxal phosphate (Vitamin B6) metabolism

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]. The pyridoxine, pyridoxamine and pyridoxal can be phosphorylated with the action of the enzyme pyridoxal kinase (PdxK) and the former two can be converted to the later by the action of pyridoxal 5’-phosphate synthase mentioned above.

 

Of the two routes mentioned above, DOXP-independent route is responsible for the de novo PLP biosynthesis in apicomplexans Plasmodium falciparum, Toxoplasma gondii and Neospora caninum. The biosynthesis of PLP was detected in P. falciparum with labelling experiments by Cassera et al [2] and it is then confirmed to be DOXP-independent pathway by Wrenger et al [3]. The de novo biosynthesis of PLP via the action of Pdx1 and Pdx2 enzymes was also experimentally demonstrated in T. gondii [4]. P. falciparum genome also possesses the PdxK enzyme which catalyses phosphorylation of salvaged pyridoxal and other vitamers and its activity has also been experimentally verified [3]. The ortholog of this enzyme is also present in T. gondii and N. caninum genomes.

 

Enzyme EC Number Gene id
Aldo-keto reductase 1.1.1.- NCLIV_002950
Aldo-keto reductase 1.1.1.- NCLIV_036520
Pyridoxal 5'-phosphate synthase 1.4.3.5 NCLIV_065800
Pyridoxal kinase 2.7.1.35 NCLIV_006190
Phosphatase 3.1.3.- NCLIV_004110
Phosphatase 3.1.3.- NCLIV_042340
Pdx2 none NCLIV_023440
Pdx1 none NCLIV_051000

 

Open in a new window

 

 

Sources and fates of metabolites

 

Substrate Source pathways Product Fate pathways
Glutamine Glutamate metabolism Glutamate Glutamate metabolism
D-Ribulose-5P Pentose phosphate cycle    
Glyceraldehyde-3P Glycolysis    
Pyridoxal Host 4-Pyridoxate ?
Pyridoxine Host    
Pyridoxamine Host    




Pyridoxal phosphate dependent enzymes in N. caninum genome

 

Enzyme EC Number Gene id
Serine hydroxymethyltransferase 2.1.2.1 NCLIV_049400
5-Aminolevulinate synthase 2.3.1.37 NCLIV_027820
Serine C-palmitoyltransferase 2.3.1.50 NCLIV_042840
Serine C-palmitoyltransferase 2.3.1.50 NCLIV_042850
Aspartate transaminase 2.6.1.1 NCLIV_064760
Ornithine aminotransferase 2.6.1.13 NCLIV_037280
Branched-chain amino acid aminotransferase 2.6.1.42 NCLIV_006760
Branched-chain amino acid aminotransferase 2.6.1.42 NCLIV_023450
Aromatic amino-acid transaminase 2.6.1.57 NCLIV_049590
Cysteine desulfurase 2.8.1.7 NCLIV_001395
Cysteine desulfurase 2.8.1.7 NCLIV_011790
Cysteine desulfurase 2.8.1.7 NCLIV_064600
Lysine decarboxylase 4.1.1.18 NCLIV_019490
Lysine decarboxylase 4.1.1.18 NCLIV_039490
Lysine decarboxylase 4.1.1.18 NCLIV_050620
Phosphatidylserine decarboxylase 4.1.1.65 NCLIV_036670
Phosphatidylserine decarboxylase 4.1.1.65 NCLIV_047160
Alanine racemase 5.1.1.1 NCLIV_010840