Pattern of Adaptive Control of Levels of Rat Liver Tryptophan Transaminase

Civen, Morton; Knox, W. Eugene

doi:10.1126/science.129.3364.1672

Cited by 21 publications

(12 citation statements)

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“…14C from L-[carboxy-"4C]tryptophan may be eliminated at several stages of tryptophan metabolism: (i) as [1-14Clalanine by the action of kynureninase on L-kynurenine or 3-hydroxy-Lkynurenine (McDermott et al, 1973); (ii) as 14CO2 by decarboxylation of tryptophan to tryptamine (Weissbach et al, 1959); rapid conversion of [1-14C]alanine into [1-14Clpyruvate by high alanine aminotransferase activity in liver and the subsequent oxidative decarboxylation of pyruvate would lead to the appearance of label as 14CO2; (iii) as 14CO2 by oxidation of indol-3-ylpyruvate to indol-3-ylacetate after transamination of tryptophan with 2-oxoglutarate (Civen & Knox, 1959); (iv) as 14CO2 by decarboxylation of 5-hydroxytryptophan to 5-hydroxytryptamine after metabolism of tryptophan by tryptophan hydroxylase.…”

Section: Resultsmentioning

confidence: 99%

“…Studies with cell-free extracts have shown that, in addition to enzymes required for the kynurenine pathway, the liver possesses the necessary enzymic complement for the catabolism of tryptophan by each of the other three pathways (Weissbach et al, 1959;Civen & Knox, 1959;Renson et al, 1966 Cell incubation conditions and assay procedures (i) Measurement of radioisotope release from radioisomers of L-tryptophan. The incubation conditions for determining rates of 14CO2 production from "4C-labelled tryptophan radioisomers were identical with those described previously (Smith & Pogson, 1980).…”

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confidence: 99%

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The metabolism of l-tryptophan by isolated rat liver cells. Quantification of the relative importance of, and the effect of nutritional status on, the individual pathways of tryptophan metabolism

Smith¹,

Carr²,

Pogson³

1980

Biochemical Journal

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1. The metabolism of L-tryptophan by liver cells prepared from fed and 48 h-starved rats was studied. Methods are described, with the use of L-[ring-2-14C], L-[carboxy-'4C1-and L-[benzene-ring-U-'4C]-tryptophan, for the simultaneous determination of tryptophan 2,3-dioxygenase and kynureninase activities and of the oxidation of tryptophan to CO2 and non-aromatic intermediates of the kynurenine-glutarate pathway. 2. At physiological concentrations (0.1 mM), tryptophan was oxidized by tryptophan 2,3-dioxygenase at comparable rates in liver cells from both fed and starved rats. Kynureninase activity of hepatocytes from starved rats was 50% greater than that of cells from fed rats. About 10%o of the tryptophan metabolized by tryptophan 2,3-dioxygenase was degraded completely to CO2. 3. In the presence of 0.5mm-L-tryptophan, tryptophan 2,3-dioxygenase and kynureninase activities increased 5-6-fold. Liver cells from starved rats oxidized tryptophan at about twice the rate of these from fed rats. Degradation of tryptophan to non-aromatic intermediates of the glutarate pathway and CO2 was increased only 3-fold, suggesting an accumulation of aromatic intermediates of the kynurenine pathway. 4. Rates of metabolism with 2.5 mM-L-tryptophan were not significantly different from those obtained with 0.5mM-tryptophan. 5. Rates of synthesis of quinolinic acid from 0.5mM-L-tryptophan, determined either by direct quantification or indirectly from rates of radioisotope release from L-[carboxy-"4C]-and [benzene-ring-U-'4C]tryptophan, were essentially similar. 6. At all three concentrations examined, tryptophan was degraded exclusively through kynurenine; there was no evidence of formation of either indol-3-ylacetic acid or 5-hydroxyindol-3-ylacetic acid.In the mammal, four separate pathways exist for the metabolism of L-tryptophan (see Scheme 1). These are: (i) oxidation by tryptophan 2,3-dioxygenase [L-tryptophan-02 2,3-oxidoreductase (decyclizing), EC 1.13.11.111 to kynurenine and subsequently to acetyl-CoA (the 'glutarate' pathway) or nicotinamide nucleotides (the 'NAD' pathway); (ii) transamination to yield indol-3-ylpyruvic acid, which may then be oxidized to indol-3-ylacetic acid; (iii) decarboxylation to yield the neurotransmitter tryptamine (Saavedra & Axelrod, 1973;Young et al., 1980) (Young et al., 1978). Several methods have been used to investigate the control of tryptophan oxidation by the kynurenine pathway in intact isolated liver preparations. These include measurements of rates of appearance of specific metabolites such as kynurenine (Green et al., 1976) or of removal of added tryptophan (Kim & Miller, 1969;Ng et al., 1970). The disadvantages of these methods have been discussed elsewhere (Smith & Pogson, 1980). S. A. Smith, F. P. A. Carr and C. I. Pogson kynurenine pathway has been derived from experiments with the use of specifically radiolabelled tryptophan (Altman & Gerber, 1967;Ng et al., 1970). However, interpretation of these radioisotope data is complicated because, in most instances, a racemic mixture of D-...

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Section: Resultsmentioning

confidence: 99%

mentioning

confidence: 99%

The metabolism of l-tryptophan by isolated rat liver cells. Quantification of the relative importance of, and the effect of nutritional status on, the individual pathways of tryptophan metabolism

Smith¹,

Carr²,

Pogson³

1980

Biochemical Journal

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“…This conclusion rests on studies employing drug dosage levels in the pharmacologic range and drug action period considerably longer than necessary to show a marked response to an inciting stimulus (4,6,8,13). For instance, either the intraperitoneal or intravenous injection of iV of the L-tryptophan standard dose produced a marked increase in hepatic TP activity in intact rats within 1 hour; in dogs a somewhat greater response was obtained with -£$ of this dose (2).…”

Section: Discussionmentioning

confidence: 92%

“…In view of the rapidity and sensitiveness of the mechanisms operative in these cases, and of the reduced response following adrenalectomy (Table 1), it would seem to be of rather limited usefulness to regard the function of the adrenal steroids in the intact organism solely from the standpoint of their inducing action. Furthermore, it is difficult to extract from the previously cited studies an insight into the function of the adrenal secretory product in the presence of increased plasma levels of the specific substrate (13).…”

Section: Discussionmentioning

confidence: 99%

Tryptophan Pyrrolase Induction and the Influence of Adrenocorticoids¹

Lee

Baltz

1962

Endocrinology

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“…A high level of dietary vitamin E might result in lowering the concentration of lipid peroxides in the tissues, thereby sparing the need for GSH peroxidase, the decomposer of lipid peroxides. Substrate induction is known to be an important factor for the synthesis of certain enzymes (18); for example, the activity of tryptophan pyrrolase in liver has been shown to increase in rats in response to the administration of its substrate, tryptophan (19,20). It has been shown (1 5 , 21, 22) that the accumulation of fluoresent products (believed to be products of lipid peroxidation) in tissues is related to the level of dietary vitamin E. The reduced oxidative stress might be part of the reason for lower activity of GSH peroxidase in tissues of rats given high levels of vitamin E.…”

Section: Discussion Many Factors Such As Dietary Levels Of Seleniummentioning

confidence: 99%

Vitamin E Supplementation and Glutathione Peroxidase Activity

et al. 1976

Experimental Biology and Medicine

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Vitamin E and selenium have been recognized as physiological antioxidants in the prevention of oxidative damage to tissues. Rotruck et al. (1) found that selenium was able to help prevent oxidative damage to rat erythrocytes incubated with glucose, as evidenced by decreased hemolysis and decreased hemoglobin oxidation. Vitamin E , however, protected only against hemolysis, whether with or without glucose, but did not prevent hemoglobin oxidation. These results indicated that the effect of selenium was specific and distinct from that of vitamin E. Later, it was demonstrated by Rotruck et al.(2) that selenium was an integral and essential part of glutathione (GSH) peroxidase. Glutathione peroxidase was reported to be responsible for the destruction of lipid peroxides in cells (3,4). Reduced GSH is a hydrogen donor for the GSH peroxidase reaction and is itself regenerated through the reaction of GSH reductase, using NADPH from the oxidation of glucose in the phosphogluconate pathway ( 2 , 3 , 5 ) . Noguchi et al. (6) showed that GSH peroxidase was present mainly in cytosol and the plasma while the action of vitamin E was thought to be primarily within the membrane. A new hypothesis (2, 5 , 6) is now being presented that vitamin E functions by neutralizing the free radicals at the site of their formation whereas GSH peroxide appears to be involved in the intracellular decomposition of lipid hydroperoxides formed. However, the relationship between dietary vitamin E supplementation and activity of GSH peroxidase in tissues has not been thoroughly investigated. The present study was undertaken to investigate the effects of a wide range of dietary vitamin E supplementation (from 0 to 25,000 IU vitamin E/kg diet) on the activity of GSH Supported by the National Research Council of Canada, Grant No. A-4686 and University of British Columbia Research Grant.peroxidase in some tissues, such as the liver, plasma, and uterus of female rats.Materials and methods. Female weanling rats of Wistar strain weighing approximately 50 g were randomly divided into six groups with four rats in each group. Food and water were supplied ad libitum. The basal tocopherol-deficient diet of Draper et al. (7), with supplements of 0, 25, 250, 2500, 10,000, and 25,000 IU vitamin E (df-a-tocopheryl acetate)/kg diet was fed to six groups of rats for 8 months. Blood samples were taken from the inferior vena cava after anesthetizing the animals with ether, and the liver and uterus were removed. The plasma, liver, and uterus were frozen and stored until further analysis. The liver and uterus were minced and then homogenized in 5 vol of KCl (0.124 M ) first with a Sorvall microhomogenizer attached to an omnimixer and then with a motor-driven Potter-Elvehjem homogenizer. The homogenate was subjected with osmotic shock to facilitate release of GSH peroxidase from mitochondria. The activity of GSH peroxidase in diluted homogenate of liver, uterus, and diluted plasma was determined by Mills' procedure 2 (8) with the modification of Hafeman et al. (9). The pr...

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Pattern of Adaptive Control of Levels of Rat Liver Tryptophan Transaminase

Cited by 21 publications

References 4 publications

The metabolism of l-tryptophan by isolated rat liver cells. Quantification of the relative importance of, and the effect of nutritional status on, the individual pathways of tryptophan metabolism

The metabolism of l-tryptophan by isolated rat liver cells. Quantification of the relative importance of, and the effect of nutritional status on, the individual pathways of tryptophan metabolism

Tryptophan Pyrrolase Induction and the Influence of Adrenocorticoids¹

Vitamin E Supplementation and Glutathione Peroxidase Activity

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Pattern of Adaptive Control of Levels of Rat Liver Tryptophan Transaminase

Cited by 21 publications

References 4 publications

The metabolism of l-tryptophan by isolated rat liver cells. Quantification of the relative importance of, and the effect of nutritional status on, the individual pathways of tryptophan metabolism

The metabolism of l-tryptophan by isolated rat liver cells. Quantification of the relative importance of, and the effect of nutritional status on, the individual pathways of tryptophan metabolism

Tryptophan Pyrrolase Induction and the Influence of Adrenocorticoids1

Vitamin E Supplementation and Glutathione Peroxidase Activity

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Product

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About

Tryptophan Pyrrolase Induction and the Influence of Adrenocorticoids¹