The Hormonal Control of Tryptophan Peroxidase in the Rat

Knox, W. Eugene; Auerbach, Victor H.

doi:10.1016/s0021-9258(18)70969-1

Cited by 387 publications

(14 citation statements)

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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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“…after hormone administration. Tryptophan pyrrolase activities were measured on fresh liver by four methods: with whole homogenate (Knox & Auerbach, 1955), with cell sap and with cell sap plus haematin (Feigelson & Greengard, 1961), and with preincubated cell sap (Knox et al 1966). Activities are given as means + S.D.…”

Section: Resultsmentioning

confidence: 99%

“…The percentage inhibition of induction was calculated from the average activities from five control and five treated rats for each point on the curve. Tryptophan pyrrolase activity was assayed by the whole-homogenate method of Knox & Auerbach (1955). Experimental details are given in the text.…”

Section: Resultsmentioning

confidence: 99%

“…A88ay of tryptophan pyrrolase. Tryptophan pyrrolase was generally determined on whole-liver homogenates by the method of Knox & Auerbach (1955). In some experiments, as indicated in the text, the enzyme was assayed by three additional methods: on cell sap and on cell sap plus haematin by the methods of Feigelson & Greengard (1961) and on preincubated cell sap by the method of Knox, Piras & Tokuyama (1966).…”

Section: Methodsmentioning

confidence: 99%

“…of liver/hr. at 370) from individual duplicate assays on five rats measured by the assay method of Knox & Auerbach (1955).…”

Section: Methodsmentioning

confidence: 99%

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Effect of dimethylnitrosamine on enzyme induction in rat liver

Shank

1968

Biochemical Journal

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1. The effects of various doses of dimethylnitrosamine on the hydrocortisone induction of tryptophan pyrrolase were studied. A single LD(50) dose of dimethylnitrosamine inhibits the synthesis of the enzyme if given within the first 5hr. of the induction. A quarter of this dose also inhibits the synthesis of the enzyme, but, in addition, retards the rate of decay of the enzyme. 2. A single small dose of dimethylnitrosamine significantly inhibits the hydrocortisone induction of tryptophan pyrrolase for at least 14 days without causing widespread damage to liver substructure. 3. The inhibition by dimethylnitrosamine of induced tryptophan pyrrolase synthesis is probably independent of any action of the toxin on the synthesis of cofactors necessary for full expression of the enzyme's activity. Dimethylnitrosamine appears to act directly on the synthesis of the enzyme protein. 4. The synthesis of that form of the enzyme which is most sensitive to hydrocortisone is apparently also most susceptible to the action of dimethylnitrosamine. 5. It is suggested that the inhibition of protein synthesis by dimethylnitrosamine may be a result of methylation of messenger RNA, which then is unable to code effectively for amino acid polymerization.

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