Pyridoxal 5′ phosphate (PLP)
4, the active form of vitamin B-6, is involved in a wide variety of physiologic processes including gluconeogenesis and the synthesis of sphingolipids and neurotransmitters. It also functions as a cofactor for many enzymes required for amino acid metabolism...
...In this issue of the Journal, Ulvik et al (
3) use these data to identify a new serum marker for examining functional vitamin B-6 status. To achieve this, they measured several metabolites in the tryptophan-to-kynurenine pathway. As shown in their Figure 1, tryptophan is metabolized to kynurenine via either indoleamine 2,3 dioxygenase (IDO1 or IDO2) or tryptophan 2,3 dioxygenase (TDO). Other than 3-hydroxykynurenine (HK), all subsequent metabolites require a vitamin B-6 (PLP)–dependent enzyme for generation. They show that ratios of HK to metabolites downstream of PLP-dependent enzymes [xanthuranic acid (XA), 3-hydroxylanthranilic acid (HAA), and kynurenic acid] correlate with PLP concentrations better than HK alone. The relation was strongest at the lowest PLP concentrations, and importantly, the ratios normalized after vitamin B-6 supplementation was instituted...
...For example, the immunomodulatory capacities of IDO are in part driven by kynurenines directly suppressing inflammatory T cell responses (
5). This same mechanism likely supports tumoral immune escape in IDO- and TDO-expressing cancers. Both kynurenine and quinolinic acid (another kynurenine metabolite downstream of PLP-dependent enzymes) directly support tumor cell proliferation by activating
β-catenin signaling in colon tumors (
6). This pathway also promotes tumor growth through activation of the human aryl hydrocarbon receptor in other tumor types (
7). Kynurenine itself also has vasodilatory properties and perhaps acts as a compensatory mechanism in atherosclerotic coronary disease (
8). Finally, several of the kynurenine metabolites have neuromodulator effects that are predicted to play important roles in both psychiatric and neurodegenerative disorders
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4498264/