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
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4498264/ which is going to be less available under inflammation/immune conditions per some of the info from my other posts. such as the lowered uptake and unavailability of zinc for example during inflammation/infection states. kynureninase (kynase) is a Vitamin B6 PLP dependent enzyme that catalyses the cleavage of kynurenine (Kyn) into anthranilic acid (Ant). It can also act on 3-hydroxykynurenine (to produce 3-hydroxyanthranilate). This is part of the pathway for the catabolism of Trp and the biosynthesis of NAD cofactors from tryptophan (Trp). The other PLP-dependent enzyme of the KP, KAT, is also subject to inhibition in B6 deficiency or perhaps not getting utilized under inflammation as I am finding.
Vitamin B6 deficiency also lowers NAD since conversion is impaired.
About 95% of TRP is metabolized through the kynurenine )KYN) pathway to produce NAD.
TRP- or indoleamine-2,3-dioxygenases (TDO or IDO) convert TRP to KYN and the activity of these enzymes is a rate-limiting step, increased by stress hormones or inflammatory factors (e.g., IFNG and LPS). KYN is then converted in 3-hydroxykynurenine (3-HKYN), through the action of KYN-monooxygenase (KMO). KYN and 3-HKYN can be converted, respectively, in kynurenic acid (KYNA) and xanthurenic acid (XA), through the activity of the aminotransferases (KAT), which is a PLP-dependent enzyme. The conversion of 3-HKYN into the 3-hydroxyanthranilic acid (3-HAA) is performed by kynureninase (KYNU), which also depends on PLP for its activity. As KYNU is more sensitive to deficiency of PLP, with respect to KAT, PLP deficiency diverts 3-HKYN metabolism from the formation of 3-HAA, to accumulation of KYNA and XA (and away from NAD).
https://www.researchgate.net/public...iabetes_Relationship_and_Molecular_Mechanisms
However most recently it appears that zinc and magnesium are cofactors that also are needed for B6 entry into the cell I found as well, so zinc and magnesium deficiency/unavailability may further impair utilization of vitamin B6 during inflammation/infection states even when supplementing such as using the active form P5P.
This may be why B6 levels become high instead during that time potentially instead.
https://forums.phoenixrising.me/thr...duction-utilization.57030/page-3#post-2440317
