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 |
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 |
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