Tryptophan-niacin Metabolism Research Articles

Tryptophan-niacin metabolism in alloxan diabetic rats and partial prevention of alloxan diabetes by nicotinamide.

After male rats of the Sprague Dawley strain, 5 weeks old, were fed a 20% casein diet with or without 0.5% nicotinamide for 13 days, 180 mg/kg body weight of alloxan was injected in- traperitoneally into the rats. The rats were kept for 18 days with the same diet. The level of blood glucose was increased 6-fold in the group on a 20% casein diet by the injection of alloxan, while there was only a 2-foid increase in the group on a nicotinamide-containing diet and the decreased body weight was also lower in the group on the nicotinamide diet than the group on the casein diet. The body weight was indirectly related to the concentration of blood glucose. A marked increase was observed in the activities of tryptophan oxygenase, aminocarboxymuconate-semialdehyde decarboxylase, and nicotinamide methyltransferase upon the injection of alloxan with both diets; on the other hand, the activities of kynureninase and NAD+ synthetase were decreased by the injection of alloxan. The activity of kynurenine aminotransferase...

Alteration of Tryptophan-Niacin Metabolism by Hormones and Nutrients

Alteration of Tryptophan-Niacin Metabolism by Hormones and Nutrients

Suppressive effect of dietary unsaturated fatty acids on alpha-amino-beta-carboxymuconate-epsilon-semialdehyde decarboxylase, a key enzyme of tryptophan-niacin metabolism in rat liver.

The effect of dietary fat on the activity of rat liver alpha-amino-beta-carboxymuconate-epsilon-semialdehyde decarboxylase [EC 4.1.1.45] (ACMSD), a key enzyme of tryptophan-niacin metabolism, was investigated. When high-fat diet was given to rats for a week, the activity of ACMSD in the liver was extremely suppressed, but not in the kidney. The liver enzyme activity was correspondingly and constantly reduced half by increasing soybean oil in the diet in 4% stages. The potency of suppression of the enzyme activity in liver was found to be different between soybean oil and lard in diets. Among various dietary fatty acids, saturated fatty acid was observed to be less effective. Unsaturated fatty acids, however, were shown to be suppressive and polyunsaturated fatty acid such as linoleic and linolenic acids more effective than oleic acid in suppressing liver ACMSD activity. These suppressive effects of dietary unsaturated fatty acids on the liver ACMSD activity were not considered to be caused by their direct effect on the enzyme protein. Moreover, neither inhibitor nor activator was thought to be involved in the alteration of the enzyme activity.

Tryptophan metabolism in alcoholic pellagra patients: measurements of urinary metabolites and histochemical studies of related muscle enzymes

Biochemical and enzymatic aspects of tryptophan-niacin metabolism were studied in 15 adult alcoholic pellagra patients and in 14 controls. In addition to the clinical signs of niacin deficiency, most of the pellagra patients had other signs of malnutrition. Plasma tryptophan in pellagra patients was 2.07 +/- 1.27 mumol/dl, and in the controls 4.84 +/- 2.21 mumol/dl (p less than 0.001). The erythrocyte glutamic oxaloacetic transaminase index was 1.94 +/- 0.77 in the pellagra patients and 1.58 +/- 0.73 in the controls. The urinary levels of 3-hydroxyanthranilic acid were 34.49 +/- 21.47 mumol/g of creatinine in the pellagra patients and 14.51 +/- 8.02 mumol/g creatinine in the controls (p less than 0.02). The urinary levels of N'methylinicotinamide were 2.13 +/- 1.18 mg/g creatinine in the pellagra patients and 4.76 +/- 1.94 mg/g creatinine in the controls (p less than 0.01). The excretion of N'-methyl-2-pyridone-5-carboxamide (2-pyridone) was 2.94 +/- 2.37 mg/g creatinine in the pellagra patients and 10.19 +/- 7.49 mg/g creatinine in the controls (p less than 0.01). The histoenzymological activity of 3-hydroxyanthranilate oxidase in the deltoid muscle was higher in the pellagra patients than in the controls, whereas alpha-glycerophosphate dehydrogenase activity was higher in the controls. These results suggest that for alcoholic pellagra patients the tryptophan-niacin pathway is inhibited after the 3-hydroxyanthranilate oxidase step.

Effects of leucine/isoleucine ratio in amino acid mixture-diets simulating normal and high-lysine maize proteins on growth, nitrogen balance, and tryptophan-niacin metabolism in rats.

To re-evaluate nutritive values of opaque-2 (o2) and brittle-2 opaque-2 (bt2o2) maize protein and to re-estimate Gopalan's hypothesis [Lancet, i, 954-957 (1960)] that pathogenesis of pellagra might be related with intake of excess leucine and with chronic consumption of maize or jowar which contains relative high leucine, rats were fed on synthetic diets composed of amino acid mixtures simulating the protein of normal and high-lysine maize, o2 and bt2o2 maize. In order to investigate the effect of intake of excess leucine, leucine was supplemented to o2 and bt2o2 diet at the level of 0.43 and 0.73%, respectively, to adjust the ratio of leucine to isoleucine to that of normal maize protein. Judging from body weight gains and carcass nitrogen of weanling rats fed on these diets, the protein quality (amino acid composition) of bt2o2 maize was 30% superior nutritionally to that of o2 maize, and body composition of bt2o2 diet group were similar to that of casein diet group. Leucine supplementation did not affect these values except for a significant decrease in plasma valine levels. In young adult rats fed on leucine supplemented o2 diet, excretion of urinary nitrogen increased significantly compared with o2 diet alone, suggesting that a slight amino acid imbalance took place. But leucine supplementation altered neither N1-methylnicotinamide level in urine nor total niacin levels in the liver and the brain. These results suggest that supplementation of leucine to a high lysine maize diet did not affect tryptophan and niacin metabolism in rats under these conditions.

Regulation of tryptophan-niacin metabolism by hormones.

The regulation of tryptophan-niacin metabolism by pituitary and adrenocortical hormones was investigated. Hypophysectomized rats fed on a niacin-free purified diet were injected with bovine somatotropin, predonine acetate or both. The urinary excretion of N-methylnicotinamide (MNA) and N-methyl-2-pyridone-5-carboxamide (2-Py) after oral administration of tryptophan was then compared before and after the hormone treatment. The amount of urinary MNA was found to be increased after the injection of somatotropin, but decreased after the predonine injection. On the other hand, no change in urinary MNA was observed in the rats administered with both hormones. The amount of 2-Py appeared to be reduced by the predonine treatment, but was not affected by somatotropin injection. The activity of liver alpha-amino-beta-carboxymuconate-epsilon-semialdehyde decarboxylase (picolinic carboxylase) was shown to be directly proportional to the ratio (oral tryptophan)/(urinary MNA). Moreover, the enzyme activity appeared to be inversely proportional to the concentration of niacin in liver. In addition, the amount of urinary MNA was suggested to be affected by the change of body weight gain. The administration of both pituitary hormone and insulin failed to normalize the reduced urinary MNA excretion in diabetic rats, suggesting that any change in pituitary hormone was not responsible for the abnormal tryptophan-niacin metabolism in diabetes.

Regulation of tryptophan-niacin metabolism in diabetic rats.

The regulation of tryptophan-niacin metabolism was studied in vivo with regard to the activity of liver α-amino-β carboxymuconate-e-semialdehyde decarboxylase (picolinic carboxylase) using non-diabetic and diabetic rats. Non-diabetic rats and rats with diabetes induced by alloxan were fed on a commercial diet for 80 days, followed by a niacin-free experimental diet for the next 16 days. Protamine zinc insulin (5 units/head) was injected into 3 diabetic rats every 12 hr from the 10th to 16th day of the start of administration of the experimental diet. At the 14th day of the experimental diet, 24-hr urine was collected and urine collection repeated after the oral administration of L-tryptophan (100mg/rat). At the end of the metabolic experiments, the content of total nicotinate in liver was determined and the enzyme activity of liver picolinic carboxylase was assayed. The urine was analyzed for N-methylnicotinamide (MNA). The amount of urinary excreted MNA per diet or per administered tryptophan was significantly reduced in diabetes, and insulin treatment rather lessened the amount in spite of normal blood glucose levels. Although the activities of liver picolinic carboxylase in diabetic and insulin-treated diabetic rat groups were higher than that of non-diabetic groups, no difference was observed between the former two groups. As the content of total nicotinate in liver was found to be almost constant among these three groups, the reduction of the urinary MNA in the insulin-treated group is considered to be attributable to the elevated retention of nicotinate that is associated with the increased weight gain. The activity of liver picolinic carboxylase was found to be inversely proportional to the amount of urinary excreted MNA and appeared to be roughly proportional to the ratio, of the amount of L-tryptophan administered to the urinary MNA. Thus, the amount of tryptophan required to produce a constant amount of MNA is expected to increase proportionally according to the elevation of the activity of liver picolinic carboxylase.

Effect of pituitary hormones on alpha-amino-beta-carboxymuconate-epsilon-semialdehyde decarboxylase in rat.

The hormonal regulation of α-amino β-carboxymuconate-e-semialdehyde decarboxylase (picolinic carboxylase) was studied to clarify the change of tryptophan-niacin metabolism in the different physiological states. Hypophysectomized rats were administered with predonine hemisuccinate and various kinds of pituitary hormones for 2 or 4 days every 12 hr. The activity of their liver picolinic carboxylase was then assayed. The injection of predonine alone elevated the enzyme activity in hypophysectomized rats. On the other hand, rat or bovine pituitary extract was found to suppress such enzyme induction when it was administered prior to predonine injection. The enzyme-suppressing activity of the pituitary extract was lost by heat treatment or addition of proteolytic enzyme such as trypsin and chymotrypsin. These results indicate that the effective substances in the extract may be polypeptides. By gel filtration of bovine pituitary extract, two effective fractions were obtained, which were able to suppress the predonine-dependent induction of liver picolinic carboxylase. The molecular weights of these substances were estimated to be about 23, 000 and 2, 000-4, 000, respectively. Both of these effective substances were shown to be localized in the anterior lobe of hypophysis. In the many kinds of pituitary hormones tested, bovine somatotropin and mammalian prolactin were found to be effective in suppressing the predonine-dependent induction of liver picolinic carbo xylase in hypophysectomized rats. To obtain some information on the mechanism by which liver picolinic carboxylase activity is elevated in diabetic rats, bovine somatotropin or rat pituitary extract was administered to diabetic rats for 4 or 7 days every 12 hr. This hormone treatment was not observed to depress the enzyme activity in the diabetic rats. These results are considred to suggest that changes in pituitary hormone are not responsible for the elevation of the enzyme activity in the diabetic rat.

Effect of leucine on enzymes of the tryptophan–niacin metabolic pathway in rat liver and kidney

Dietary excess of leucine affects tryptophan-niacin metabolism adversely and has thus been implicated in the etiology of pellagra. To understand the biochemical basis of leucine-induced changes in tryptophan-niacin metabolism the effect of leucine on enzymes of tryptophan-niacin metabolism was investigated. Excess of leucine in the diet had no effect on rat liver 3-hydroxyanthranilate oxygenase and nicotinate phosphoribosyltransferase but significantly decreased the activity of quinolinate phosphoribosyltransferase of rat liver and kidney. The activities of tryptophan oxygenase in liver and picolinate carboxylase in kidney were significantly higher in leucine-fed animals than in the controls. Also, oxidation of [U-(14)C]tryptophan in vivo was higher in leucine-fed animals. Increased picolinate carboxylase and decreased quinolinate phosphoribosyltransferase activities would result in a decrease in NAD formation from dietary tryptophan. Lowered NAD formation from tryptophan particularly when the niacin concentrations in the diet are marginal would result in a state of conditioned niacin deficiency.

Tryptophan-niacin Metabolism: I. Pregnancy, Ovarian Hormones and Levels of Tryptophan Intake as Factors Affecting the Tryptophan-Niacin Metabolism of the Rat

Tryptophan-niacin Metabolism: I. Pregnancy, Ovarian Hormones and Levels of Tryptophan Intake as Factors Affecting the Tryptophan-Niacin Metabolism of the Rat