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 and Toxoplasma gondii. 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 genome.

 

Protein EC Number Gene id Protein localisation Localisation data source
Aldo-keto reductase 1.1.1.- TGME49_208040    
Aldo-keto reductase 1.1.1.- TGME49_270100    
Pyridoxal 5'-phosphate synthase 1.4.3.5 TGME49_249650 Mitochondrion Previous publication
Pyridoxal kinase 2.7.1.35 TGME49_297080 Cytoplasm-nuclear Previous publication
Phosphatase 3.1.3.- TGME49_209870    
Phosphatase 3.1.3.- TGME49_289980    
Pyridoxal 5'-phosphate synthase - Pdx1 (part of PLP synthase complex) none TGME49_237140 Cytosol Previous publication
Glutamine amidotransferase - Pdx2 (part of PLP synthase complex) none TGME49_281490    

 

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 T. gondii genome

 

Enzyme EC number Gene id Protein localisation Localisation data source
Serine hydroxymethyltransferase (SHMT) 2.1.2.1 TGME49_234190 Cytoskeleton Previous publication
Aminolevulinate synthase 2.3.1.37 TGME49_258690    
Serine C-palmitoyltransferase 2.3.1.50 TGME49_290970    
Serine C-palmitoyltransferase 2.3.1.50 TGME49_290980    
Aspartate transaminase 2.6.1.1 TGME49_248600 Cytosol Previous publication
Ornithine aminotransferase 2.6.1.13 TGME49_269110    
Branched-chain-amino-acid-transaminase 2.6.1.42 TGME49_281500    
Branched-chain-amino-acid-transaminase 2.6.1.42 TGME49_297850    
Aromatic-amino-acid transaminase 2.6.1.57 TGME49_234440    
Cysteine desulfurase 2.8.1.7 TGME49_211090 Apicoplast Previous publication
Cysteine desulfurase 2.8.1.7 TGME49_294380    
Cysteine desulfurase 2.8.1.7 TGME49_300120 Apicoplast Previous publication
Lysine decarboxylase 4.1.1.18 TGME49_236570 Nucleus Previous publication
Lysine decarboxylase 4.1.1.18 TGME49_280700    
Phosphatidylserine decarboxylase 4.1.1.65 TGME49_225550 Apicoplast Previous publication
Phosphatidylserine decarboxylase 4.1.1.65 TGME49_269920 Cytosol Previous publication
Alanine racemase 5.1.1.1 TGME49_318720