Tryptophan metabolism in patients with pellagra: problem of vitamin B6 enzyme activity and feedback control of tryptophan pyrrolase enzyme

Kynurenines: from the perspective of major psychiatric disorders

“…Vitamin B6 plays an important role in the metabolism since pyridoxyl 5‐phosphate, the co‐enzyme in the KYN pathway, is derived from this vitamin. The effect of vitamin B6 could be observed not only in conditions associated with B6 deficiencies but also in healthy conditions, since vitamin B6 supplementation to healthy subjects can influence the enzyme activities and formation of metabolites [8,9]. In the case of impaired function of this co‐enzyme, urinary excretion of KYN, OHK and xanthurenic acid (XAN) are increased because of the reduced activity of kynureninase which converts the OHK and XAN into HAA, the activity of which is sensitive to the activity of the co‐enzyme [7,10].…”

Pellagra: a still existing disease

“…It has been reported that 50% of the Bantu who were examined in the various clinics for a number of diseases presented with skin manifestations of pellagra (Pretorious, 1968). The increase of the disease among the Bantu has also been shown by Findlay et al (1969) and Hankes et al (1971). Adrian et al (1972) also observed that the disease is endemic in a few areas of Western Africa, notably Angola.…”

“…The possible role of vitamin B6 has been pointed out by Hankes et al (1971) who administered a diet enriched with L-tryptophan to pellagra patients. They found increased quantities of two or more metabolites of tryptophan in the urine of these patients arising from the kynurenin pathway, returning to normal following the administration of pyridoxine.…”

Two complex genotypes relevant to the kynurenine pathway and melanotropin function show association with schizophrenia and bipolar disorder

“…To the list of neurotoxic products should be added the pigment products of 3-hydroxykynurenine and 3-hydroxyanthranilic acid as the elevation in pathway intermediates extends through to 3-hydroxyanthranilic acid in schizophrenia (Miller et al, 2008). This interpretation of the pathophysiology relates to the gene-gene interaction of HM74A and MCHR1 (Model 2 in Figure 1, wherein the pigment products may not be adequately sequestered when the risk genotype for MCHR1 is present combined with the risk genotype for HM74A, as the ligand for HM74A (niacin) controls levels of kynurenine pathway products in human subjects (Hankes et al, 1971). The types of kynurenine pathway pigments range from the xanthomattins, a form that predominates in the eye and thought to be involved in cataract formation (Vazquez et al, 2000) to the melanin family of pigments (Vogliardi et al,2004), to the antibiotic, cinnabarinic acid (Vazquez et al, 2000).…”

“…The models (see Discussion) for the relevant points of potential interaction between the melanotropin receptors and the kynurenine pathway genes, gene products or metabolites are denoted models 1, 2, and 3. Note that the regulatory role of the niacin receptor genes for the kynurenine pathway can only be inferred from the fact that administration of niacin does not allosterically inhibit TDO2 to any significant extent, but by some other means, leads to remission of the kynurenine-mediated de-novo synthesis of NAD from tryptophan in pellagra patients (Hankes et al, 1971). Niacin treatment of schizophrenia patients has been reported to result in remission of psychosis (Hoffer et al, 1957).…”