Effects of Dietary Pyrazinamide, an Antituberculosis Agent, on the Metabolism of Tryptophan to Niacin and of Tryptophan to Serotonin in Rats

  title={Effects of Dietary Pyrazinamide, an Antituberculosis Agent, on the Metabolism of Tryptophan to Niacin and of Tryptophan to Serotonin in Rats},
  author={Katsumi Shibata and Tsutomu Fukuwatari and Etsuro Sugimoto},
  journal={Bioscience, Biotechnology, and Biochemistry},
  pages={1339 - 1346}
The effects of pyrazinamide on the metabolism of tryptophan to niacin and of tryptophan to serotonin were investigated to elucidate the mechanism for pyrazinamide action against tuberculosis. Weanling rats were fed with a diet with or without 0.25% pyrazinamide for 61 days. Urine samples were periodically collected for measuring the tryptophan metabolites. The administration of pyrazinamide significantly increased the metabolites, 3-hydroxyanthranilic acid and beyond, especially quinolinic acid… 
Growth-promoting Activity of Pyrazinoic Acid, a Putative Active Compound of Antituberculosis Drug Pyrazinamide, in Niacin-deficient Rats through the Inhibition of ACMSD Activity
Results suggest that a derivative of POA metabolized by rats inhibited the ACMSD activity, the rate-limiting enzyme in the tryptophan-niacin pathway.
Effects of Fatty Liver Induced by Niacin-free Diet with Orotic Acid on the Metabolism of Tryptophan to Niacin in Rats
The conversion ratio of tryptophan to niacin significantly decreased in the test group in comparison with the control group, and the concentrations of NAD and NADP in liver significantly decreased, while these in blood did not decrease compared to thecontrol group.
Effects of Fatty Liver Induced by on the Metabolism of TryptophanNiacin-free Diet with to Niacin in RatsOrotic AcidJSIst
The effects of dietary orotic acid on the metabolism of tryptophan to niacin in weaning rats was investigated. The rats vvere fed vvith a niacin-free, 20% casein diet containing O% (controt diet) or
Effects of Excess Nicotinamide Administration on the Urinary Excretion of Nicotinamide N-Oxide and Nicotinuric Acid by Rats
Results show that the measurements of Nicotinamide N-oxide and nicotinuric acid in urine would be useful indices for an excessive nicotinamide intake.
The metabolites in the tryptophan degradation pathway might be useful to determine the tolerable upper intake level of tryptophan intake in rats.
The aim of the present workshop was to identify biomarkers that could be used before the appearance of adverse effects of L-Trp, and it is shown that the urinary excretory ratio of anthranilic acid:kynurenic acid is potentially the most sensitive and appropriate surrogate breakpoint index to predict the UL.
Organ Co-Relationship in Tryptophan Metabolism and Factors That Govern the Biosynthesis of Nicotinamide from Tryptophan.
  • K. Shibata
  • Chemistry, Medicine
    Journal of nutritional science and vitaminology
  • 2018
The findings indicate that QPRT is not the rate-limiting enzyme in the conversion of Trp to nicotinamide, and the limiting factors in the Conversion are the amounts of 3-hydroxyanthranilic acid and quinolinic acid in the liver and the activity of liver 3-Hydroxyanic acid 3,4-dioxygenase.
Pyrazinamide may possess cardioprotective properties
It is concluded that pyrazinamide increases resistance to metabolic stress in heart H9c2 cells probably by increasing SUR2A and SUR2B expression.
Nutritional Aspect of Tryptophan Metabolism
It is suggested that the conversion of nicotinamide from tryptophan is important in maintaining niacin nutrition and contributed to the determination of dietary reference intakes for niacIn recommended in the Dietary Reference Intakes for Japanese 2010.
Changes in the urinary excretion of the metabolites of the tryptophan-niacin pathway during pregnancy in Japanese women and rats.
The urinary excretions of niacin metabolites in humans and rats increased from mid pregnancy in a time-dependent manner, reached a peak of 2-3-fold during late pregnancy, and declined to control levels after childbirth.
Antioxidant and hepatoprotective effect of Macrotyloma uniflorum seed in antitubercular drug induced liver injury in rats
Horse gram [Macrotyloma uniflorum Lam. (Verdc.)] is a lesser known bean consumed as a whole seed or sprout in India. Its seeds are rich in flavonoids and phenolic acids. The protective effect of a


The effect of pyrazines on the metabolism of tryptophan and nicotinamide adenine dinucleotide in the rat. Evidence of the formation of a potent inhibitor of aminocarboxy-muconate-semialdehyde decarboxylase from pyrazinamide.
Results suggest that the glutarate pathway of L-tryptophan was strongly inhibited by the inhibitor produced after the administration of pyrazinoic acid and pyrazinamide, which exhibited a significant inhibition of the nuclear enzyme poly(ADP-ribose) synthetase in rat liver.
In vivo inhibition of kynurenine aminotransferase activity by isonicotinic acid hydrazide in rats.
The activity of kynurenine aminotransferase was significantly inhibited by feeding a diet containing INH and by an injection of INH, and the urinary excretion of xanthurenic acid, the side-reaction product of the conversion pathway of tryptophan to niacin, was below the limit of detection.
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
Simultaneous micro-determination of nicotinamide and its major metabolites, N1-methyl-2-pyridone-5-carboxamide and N1-methyl-4-pyridone-3-carboxamide, by high-performance liquid chromatography.
A simultaneous micro-determination of nicotinamide and its major metabolites, N1-methyl-2-pyridone-5-carboxamide (2-py) and N1 -methyl-4-pyrimidine-3-car boxamide (4-py), by high-performance liquid chromatography is described, applied to the analysis of rat and human urines.
Efficiency of Exogenous Quinolinic Acid as Niacin in Rats
The nutritional efficiency of quinolinic acid as a substitute for nicotinic acid was investigated using weanling rats Of the Sprague Dawley strain (3-weeks old) fed a nicotinic acid-free,
Evaluation of the teratogenic potential of pyrazinamide in Wistar rats.
Data show that in Wistar rats, only high doses of PZA (100 and 500 mg/kg) produced fetotoxicity, and no evidence of teratogenic effect of the drug was observed.
Measurement of 3-hydroxyanthranilic acid and anthranilic acid in urine by high-performance liquid chromatography
Measurements of 3-hydroxyanthranilic acid and anthranilic acid in urine are described. The urine adjusted to pH 3.0 was saturated with NaCl, and 3-hydroxyanthranilic acid and anthranilic acid were
Simultaneous High-performance Liquid Chromatographic Measurement of Xanthurenic Acid and 3-Hydroxyanthranilic Acid in Urine.
XA and 3-HA in the sample were characterized on the basis of their retention times, and by coinjecting the respective reference compounds by calculating molar absorptivity of 35,000 M- 1 .
Simple Measurement of Blood NADP and Blood Levels of NAD and NADP in Humans
iheasurement of NAD (NAD' + NADH) b}, Nisselbaum's method2} has been successfully used for the estimation of blood NAD and that blood NAD values varied depending on the niucin contents i] the diets
Reversed-phase high-performance liquid chromatography of nicotinic acid mononucleotide for measurement of quinolinate phosphoribosyltransferase.
A system has been developed for the determination of quinolinate phosphoribosyltransferase (QPRT) activity in liver and kidney homogenates using HPLC. A product, nicotinic acid mononucleotide (NaMN),