Insulin and glucagon as a new regulator system for tryptophan oxygenase activity demonstrated in primary cultured rat hepatocytes.

Nakamura, Toshikazu; Shinno, Hideki; Ichihara, Akira

doi:10.1016/s0021-9258(19)43858-1

Cited by 85 publications

(2 citation statements)

References 18 publications

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“…TDO and IDO play an important role in tryptophan homeostasis (16). Whereas TDO has been reported to be induced by tryptophan (16)(17)(18), glucocorticoids (18)(19)(20), glucagon (21), and estrogens (22), IDO is induced primarily by interferon (IFN)-g (3,12), and therefore IDO has been extensively studied in the immune response (2,14).…”

Section: Introductionmentioning

confidence: 99%

A Mathematical Model of Tryptophan Metabolism via the Kynurenine Pathway Provides Insights into the Effects of Vitamin B-6 Deficiency, Tryptophan Loading, and Induction of Tryptophan 2,3-Dioxygenase on Tryptophan Metabolites

Rios‐Avila

Nijhout

Reed

et al. 2013

The Journal of Nutrition

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Vitamin B-6 deficiency is associated with impaired tryptophan metabolism because of the coenzyme role of pyridoxal 5'-phosphate (PLP) for kynureninase and kynurenine aminotransferase. To investigate the underlying mechanism, we developed a mathematical model of tryptophan metabolism via the kynurenine pathway. The model includes mammalian data on enzyme kinetics and tryptophan transport from the intestinal lumen to liver, muscle, and brain. Regulatory mechanisms and inhibition of relevant enzymes were included. We simulated the effects of graded reduction in cellular PLP concentration, tryptophan loads and induction of tryptophan 2,3-dioxygenase (TDO) on metabolite profiles and urinary excretion. The model predictions matched experimental data and provided clarification of the response of metabolites in various extents of vitamin B-6 deficiency. We found that moderate deficiency yielded increased 3-hydroxykynurenine and a decrease in kynurenic acid and anthranilic acid. More severe deficiency also yielded an increase in kynurenine and xanthurenic acid and more pronounced effects on the other metabolites. Tryptophan load simulations with and without vitamin B-6 deficiency showed altered metabolite concentrations consistent with published data. Induction of TDO caused an increase in all metabolites, and TDO induction together with a simulated vitamin B-6 deficiency, as has been reported in oral contraceptive users, yielded increases in kynurenine, 3-hydroxykynurenine, and xanthurenic acid and decreases in kynurenic acid and anthranilic acid. These results show that the model successfully simulated tryptophan metabolism via the kynurenine pathway and can be used to complement experimental investigations.

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Section: Introductionmentioning

confidence: 99%

A Mathematical Model of Tryptophan Metabolism via the Kynurenine Pathway Provides Insights into the Effects of Vitamin B-6 Deficiency, Tryptophan Loading, and Induction of Tryptophan 2,3-Dioxygenase on Tryptophan Metabolites

Rios‐Avila

Nijhout

Reed

et al. 2013

The Journal of Nutrition

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“…The regulatory region of the tdo2 gene, containing glucocorticoid response elements, could be upregulated by dexamethasone, an anti-inflammatory glucocorticoid drug [ 130 , 252 , 253 , 254 ]. Thus, the expression of TDO is induced by glucocorticoid hormones, glucagon, estrogens, and also regulated by the availability of its substrate, TRP [ 126 , 136 , 255 , 256 , 257 , 258 , 259 , 260 ]. Moreover, there are reports indicating that TDO activation is stimulated by free radicals.…”

Section: The Potential Interaction Of the Ans And Kp In Schizophrenia And Molecules Mutually Targeting Kp And Autonomic Dysfunctions In Smentioning

confidence: 99%

A Potential Interface between the Kynurenine Pathway and Autonomic Imbalance in Schizophrenia

Büki

Kekesi

Horváth

et al. 2021

IJMS

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Schizophrenia is a neuropsychiatric disorder characterized by various symptoms including autonomic imbalance. These disturbances involve almost all autonomic functions and might contribute to poor medication compliance, worsened quality of life and increased mortality. Therefore, it has a great importance to find a potential therapeutic solution to improve the autonomic disturbances. The altered level of kynurenines (e.g., kynurenic acid), as tryptophan metabolites, is almost the most consistently found biochemical abnormality in schizophrenia. Kynurenic acid influences different types of receptors, most of them involved in the pathophysiology of schizophrenia. Only few data suggest that kynurenines might have effects on multiple autonomic functions. Publications so far have discussed the implication of kynurenines and the alteration of the autonomic nervous system in schizophrenia independently from each other. Thus, the coupling between them has not yet been addressed in schizophrenia, although their direct common points, potential interfaces indicate the consideration of their interaction. The present review gathers autonomic disturbances, the impaired kynurenine pathway in schizophrenia, and the effects of kynurenine pathway on autonomic functions. In the last part of the review, the potential interaction between the two systems in schizophrenia, and the possible therapeutic options are discussed.

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2012

Amino Acid Metabolism

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Insulin and glucagon as a new regulator system for tryptophan oxygenase activity demonstrated in primary cultured rat hepatocytes.

Cited by 85 publications

References 18 publications

A Mathematical Model of Tryptophan Metabolism via the Kynurenine Pathway Provides Insights into the Effects of Vitamin B-6 Deficiency, Tryptophan Loading, and Induction of Tryptophan 2,3-Dioxygenase on Tryptophan Metabolites

A Mathematical Model of Tryptophan Metabolism via the Kynurenine Pathway Provides Insights into the Effects of Vitamin B-6 Deficiency, Tryptophan Loading, and Induction of Tryptophan 2,3-Dioxygenase on Tryptophan Metabolites

A Potential Interface between the Kynurenine Pathway and Autonomic Imbalance in Schizophrenia

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