Urinary Excretion Of Nicotinamide Research Articles

Moderate food restriction suppresses the conversion of L-tryptophan to nicotinamide in weaning rats.

Calorie restriction leads to a change in the metabolism of nutrients. Nicotinamide is biosynthesized from L-tryptophan. We attempted to determine the effects of food restriction on the biosynthesis of nicotinamide from L-tryptophan. Weaning male rats were fed a conventional chemically defined diet without preformed niacin for 63 d. However, the food intake was restricted to 80 and 65% of the intake of the ad libitum-fed control group of rats. The 24-h urine samples were periodically collected, and the urinary excretion of nicotinamide and its catabolites was measured. The conversion percentages were lower in both restricted groups than in the ad libitum-fed control group during the experimental period (control group, 1.37 ± 0.24%; 80%-restricted group, 0.20 ± 0.04%; 65%-restricted group, 0.15 ± 0.02%; control vs. restricted groups, p < 0.01). Food restriction, even at mild level, suppressed the conversion of L-tryptophan to nicotinamide when compared to the ad libitum-fed control group.

Supplementing Healthy Women with up to 5.0 g/d of L-Tryptophan Has No Adverse Effects

Because of the frequent use of L-tryptophan (L-Trp) in dietary supplements, determination of the no-observed-adverse-effect-level is desirable for public health purposes. We therefore assessed the no-observed-adverse-effect-level for L-Trp and attempted to identify a surrogate biomarker for excess L-Trp in healthy humans. A randomized, double-blind, placebo-controlled, crossover intervention study was performed in 17 apparently healthy Japanese women aged 18–26 y with a BMI of ∼20 kg/m2. The participants were randomly assigned to receive placebo (0 g/d) or 1.0, 2.0, 3.0, 4.0, or 5.0 g/d of L-Trp for 21 d each with a 5-wk washout period between trials. Food intake, body weight, general biomarkers in blood and urine, and amino acid composition in blood and urine were not affected by any dose of L-Trp. Administration of up to 5.0 g/d L-Trp had no effect on a profile of mood states category measurement. The urinary excretion of nicotinamide and its catabolites increased in proportion to the ingested amounts of L-Trp, indicating that participants could normally metabolize this amino acid. The urinary excretion of L-tryptophan metabolites, including kynurenine (Kyn), anthranilic acid, kynurenic acid, 3-hydroxykynurenine (3-HK), 3-hydroxyanthranilic acid, and quinolinic acid (QA), all of which are intermediates of the L-Trp→Kyn→QA pathway, was in proportion to L-Trp loading. The response of 3-HK was the most characteristic of these L-Trp metabolites. This finding suggests that the urinary excretion of 3-HK is a good surrogate biomarker for excess L-Trp ingestion.

Effects of hepatic injury or kidney injury on the tryptophan–niacin metabolism in rats

Abstract Hepatic α-amino-β-carboxymuconate-e-semialdehyde decarboxylase (ACMSD) plays a key role in regulating NAD biosynthesis. In normal rats, ACMSD has been generally detectable only in the liver and kidneys. Therefore, there is a possibility that liver or kidney injury affects tryptophan–niacin metabolism. We previously reported the significant change of tryptophan–niacin metabolism in rats with liver cirrhosis or in rats with d -galactosamine injected liver injury. In this experiment, we investigated the change of tryptophan–niacin metabolism in rats treated with puromycin aminonucleoside (PAN)-induced nephrosis, the mechanisms responsible for their change of urinary excretion of nicotinamide and its metabolites, and the role of the kidney in tryptophan–niacin conversion. In PAN-treated rats, the sum of urinary excretion of nicotinamide and its metabolites was significantly lower compared with controls. Although kidney ACMSD activity was reduced, the conversion of tryptophan to niacin tended to be lower in the PAN-treated rats. The reduction of urinary excretion of niacin in nephrotic rats may be due to the reduction of blood tryptophan concentration. The role of the kidney ACMSD may be insignificant concerning tryptophan–niacin conversion under this experimental condition.

Tryptophan-Niacin Metabolism in Rat with Puromycin Aminonucleoside-Induced Nephrosis

We investigated the change of tryptophan-niacin metabolism in rats with puromycin aminonucleoside PAN-induced nephrosis, the mechanisms responsible for their change of urinary excretion of nicotinamide and its metabolites, and the role of the kidney in tryptophan-niacin conversion. PAN-treated rats were intraperitoneally injected once with a 1.0% (w/v) solution of PAN at a dose of 100 mg/kg body weight. The collection of 24-hour urine was conducted 8 days after PAN injection. Daily urinary excretion of nicotinamide and its metabolites, liver and blood NAD, and key enzyme activities of tryptophan-niacin metabolism were determined. In PAN-treated rats, the sum of urinary excretion of nicotinamide and its metabolites was significantly lower compared with controls. The kidney alpha-amino-beta-carboxymuconate-epsilon-semialdehyde decarboxylase (ACMSD) activity in the PAN-treated group was significantly decreased by 50%, compared with the control group. Although kidney ACMSD activity was reduced, the conversion of tryptophan to niacin tended to be lower in the PAN-treated rats. A decrease in urinary excretion of niacin and the conversion of tryptophan to niacin in nephrotic rats may contribute to a low level of blood tryptophan. The role of kidney ACMSD activity may be minimal concerning tryptophan-niacin conversion under this experimental condition.

Effects of excess nicotinamide administration on the urinary excretion of nicotinamide N-oxide and nicotinuric acid by rats.

We investigated a useful chemical index for an excessive nicotinamide intake and how this excessive nicotinamide intake affects the tryptophan-nicotinamide metabolism in rats. Weaning rats were fed on a tryptophan-limited and nicotinic acid-free diet containing no, 0.003%, 0.1%, 0.2%, or 0.3% nicotinamide for 21 days. Urine samples were collected on the last day and analyzed the intermediates and metabolites on the tryptophan-nicotinamide pathway. Nicotinamide N-oxide, nicotinic acid and nicotinuric acid, metabolites of nicotinamide, were detected when nicotinamide at more than 0.1% had been taken. An intake of nicotinamide of more than 0.1% increased the urinary excretion of quinolinic acid, an intermediate on the pathway. Nicotinamide N-oxide and nicotinuric acid increased with increasing dietary concentration of nicotinamide. These results show that the measurements of nicotinamide N-oxide and nicotinuric acid in urine would be useful indices for an excessive nicotinamide intake.

Change of tryptophan-niacin metabolism in D-galactosamine-induced liver injury in rat.

The change of tryptophan-niacin metabolism in D-galactosamine (D-galN) injected rats was investigated. Rats fed with niacin-free diets containing 40% casein for 11 days were injected with D-galN (0.8 g/kg body weight). The urinary excretions of nicotinamide and its metabolites, and the activity of liver alpha-amino-beta-carboxymuconate-epsilon-semialdehyde decarboxylase (ACMSD) (EC 4.1.1.45), a key enzyme of tryptophan-niacin metabolism, were assayed. As the result, the urinary excretions of N1-methylnicotinamide (MNA), N1-methyl-2-pyridone-5-carboxamide (2-Py), N1-methyl-4-pyridone-3-carboxamide (4-Py) and their sum (nicotinamide+MNA+2-Py+4-Py) were higher in the D-galN-injected group than in the control group. Hepatic ACMSD activity in the D-galN-injected group was lower than that of the control group. These results suggest that the increase in urinary excretion of nicotinamide and its metabolites after the injection of D-galN is considered to be attributable to a decrease in liver ACMSD activity.

Effects of sex hormones on the metabolism of tryptophan to niacin and to serotonin in male rats.

It is known that deaths attributable to pellagra, which is considered to be a disease caused by the disturbance of tryptophan metabolism, have been approximately two-fold higher in women than in men. We investigated the effects of the administration of female and male sex hormones on the contents of tryptophan and such metabolites as serotonin, nicotinamide, N1-methylnicotinamide, N1-methyl-2-pyridone-5-carboxamide, and N1-methyl-4-pyridone-3-carboxamide, and on the conversion ratio of tryptophan to niacin in male rats. Feeding a diet containing estrone or testosterone had no effect on the concentrations of tryptophan and serotonin in the blood and brain, or on the concentration of 5-hydroxyindole-3-acetic acid in the brain. On the contrary, feeding a diet containing estrone caused to a decrease in the urinary excretion of nicotinamide, N1-methylnicotinamide, N1-methyl-2-pyridone-5-carboxamide, and N1-methyl-4-pyridone-3-carboxamide, and of the conversion ratio of tryptophan to niacin when compared with the control rats. Feeding a diet containing testosterone had no effect on any parameter. We postulate from these findings that the cause of higher pellagra deaths in women than in men is attributable to the decrease in the formation of niacin from tryptophan, but not in the formation of serotonin by the female hormone. It seems likely that female sex hormones inhibit the synthesis of niacin from tryptophan, and that women, especially during pregnancy, will be more at risk to pellagra than are men.

Effect of Adding Branched-chain Amino Acids to a Nicotinic Acid-free, Low-protein Diet on the Conversion Ratio of Tryptophan to Nicotinamide in Rats

The effects of adding branched-chain amino acids to a nicotinic acid-free, low-protein diet on the conversion of tryptophan to nicotinamide were investigated in rats. The conversion ratio [urinary excretion of nicotinamide and its metabolites (μmol/day) × 100/tryptophan intake during urine collection (μmol/day)] was significantly lower in the groups fed with the 3% Leu-, Val-, or Ile-added diet than in the group fed with the control diet. Namely, the inhibition of this conversion was observed not only by the addition of Leu, but also by the addition of Val or Ile. The addition of Ile and/or Val to the Leu-added diet did not antagonize the Leu effect.

Increase in the Urinary Excretion of Nicotinamide and Its Metabolites in Rats Administered 3-Acetylpyridine, an Antagonist of Niacin.

Journal Article Increase in the Urinary Excretion of Nicotinamide and Its Metabolites in Rats Administered 3-Acetylpyridine, an Antagonist of Niacin Get access Katsumi Shibata, Katsumi Shibata Department of Food Science and Nutrition, Teikoku Women’s University, Moriguchi, Osaka 570, Japan Search for other works by this author on: Oxford Academic Google Scholar Junko Sumizaki, Junko Sumizaki Department of Food Science and Nutrition, Teikoku Women’s University, Moriguchi, Osaka 570, Japan Search for other works by this author on: Oxford Academic Google Scholar Michiko Onodera Michiko Onodera Department of Food Science and Nutrition, Teikoku Women’s University, Moriguchi, Osaka 570, Japan Search for other works by this author on: Oxford Academic Google Scholar Bioscience, Biotechnology, and Biochemistry, Volume 56, Issue 5, 1 January 1992, Page 825, https://doi.org/10.1271/bbb.56.825 Published: 01 January 1992 Article history Received: 28 October 1991 Published: 01 January 1992

Effects of Administration of Nicotinic Acid Related Compounds on The Growth of Rats, Food Intake, and The Urinary Excretion of Nicotinamide and Its Metabolites

Effects of Administration of Nicotinic Acid Related Compounds on The Growth of Rats, Food Intake, and The Urinary Excretion of Nicotinamide and Its Metabolites

Comparison of Tryptophan-Niacin Conversion in Rats Fed with a Nicotinic Acid-free Diet Containing Egg White, Egg White Proteolysate, or Mixtures of Amino Acids

This investigation was carried out to learn whether or not tryptophan-niacin conversion is affected by the type of tryptophan, namely protein, small peptides, and mixtures of amino acids. Growing rats were fed with a nicotinic acid-free diet containing 20% egg white (EW; tryptophan content, 0.2085%), 25% egg white proteolysate-5 (EWP-5; tryptophan content, 0.2087%), or 18.13% mixtures of amino acids (AA; tryptophan content, 0.2085%) for 10 days. Urine samples were collected on the last day of the experiment. The body weigh gain and food intake during the experiment were almost the same among the animals in the three groups, and the content of total nicotinamide in the liver in the three groups was within the normal range. Under these conditions, the apparant tryptophan-niacin conversion [urinary excretion of nicotinamide + N1-methylnicotinamdide + N1-methyl-2-pyridone-5-carboxamide + N1-methyl-4-pyridone-3-carboxamide (μmol/day)/daily tryptophan intake for urine collection (μmol/day)] in the EW, EWP-5 and AA groups was 2.3%, 0.93% and 1.45%, respectively. Therefore, it was found that the tryptophan-niacin conversion varied according to the type of tryptophan, namely protein, small peptides, and mixtures of amino acids.

Nutritional Efficiency of Nicotinamide N-Oxide and N'-Methylnicotinamide as Niacin in Rats.

The nutritional efficiency of nicotinamide N-oxide and N’-methylnicotinamide as substitutes for nicotinic acid was investigated using weanling rats fed with a nicotinic acid-free and tryptophan-limited diet (basal diet; negative control), the basal diet containing 0.003% nicotinic acid (positive control), or basal diet containing various amounts of nicotinamide N-oxide or N’-methylnicotinamide. The relative niacin activity of nicotinamide N-oxide and N’-methylnicotinamide to nicotinic acid was about 1/5 and 1/2 on a weight basis, respectively, judged from the following comparisons: body weight gain, food intake, food efficiency ratio, the NAD contents in liver and blood, the total nicotinamide content in liver, and the urinary excretion of nicotinamide and its metabolites such as N1-methylnicotinamide, N1-methyl-2-pyridone-5-carboxamide, and N1-methyl-4-pyridone-3-carboxamide.

Comparison of tryptophan-niacin conversion in rats fed with a nicotinic acid-free diet containing egg white, egg white proteolysate, or mixtures of amino acids.

This investigation was carried out to learn whether or not tryptophan-niacin conversion is affected by the type of tryptophan, namely protein, small peptides, and mixtures of amino acids. Growing rats were fed with a nicotinic acid-free diet containing 20% egg white (EW; tryptophan content, 0.2085%), 25% egg white proteolysate-5 (EWP-5; tryptophan content, 0.2087%), or 18.13% mixtures of amino acids (AA; tryptophan content, 0.2085%) for 10 days. Urine samples were collected on the last day of the experiment. The body weigh gain and food intake during the experiment were almost the same among the animals in the three groups, and the content of total nicotinamide in the liver in the three groups was within the normal range. Under these conditions, the apparant tryptophan-niacin conversion [urinary excretion of nicotinamide + N1 -methylnicotinamdide + N1 -methyl-2-pyridone-5-carboxamide + N1-methyl-4-pyridone-3-carboxamide (μmol/day)/daily tryptophan intake for urine collection (μmol/day)] in the EW, EWP-5 and AA groups was 2.3%, 0.93% and 1.45%, respectively. Therefore, it was found that the tryptophan-niacin conversion varied according to the type of tryptophan, namely protein, small peptides, and mixtures of amino acids.

Effect of Prednisolone on the Urinary Excretion of Nicotinamide and Its Metabolites in Rats Fed with a Niacin-free Diet

Adrenal cortical hormone seems to play an important role in de novo NAD biosynthesis from tryptophan. Therefore, the effects of prednisolone, a synthetic adrenal cortical hormone, on the urinary excretion of nicotinamide and such catabolic metabolites as N1-methylnicotinamide (MNA), N1-methyl-2-pyridone-5-carboxamide (2-Py) and N1-methyl-4-pyridone-3-carboxamide (4-Py) were investigated. Rats fed with a niacin-free diet were intraperitoneally injected with prednisolone (3 mg/rat) three times at 09:00, 13:00 and 17:00 hr on day 0. As a result, the urinary excretion of nicotinamide, MNA, 2-Py and 4-Py was each higher in the prednisolone group than in the physiological saline group (for control) after 1 day; however, each excretion was lower in the prednisolone group than in control group after 3, 4, 5 and 6 days. On around the 7th day, the urinary excretion in the prednisolone group was restored to the control values. The initial rapid increase and subsequent decrease in the urinary excretion of nicotinamide and its metabolites by an injection of prednisolone is considered to be attributable to a respective elevation of the liver tryptophan oxygenase level and the liver aminocarboxymuconate-semialdehyde decarboxylase level.

Effect of prednisolone on the urinary excretion of nicotinamide and its metabolites in rats fed with a niacin-free diet.

Adrenal cortical hormone seems to play an important role in de novo NAD biosynthesis from tryptophan. Therefore, the effects of prednisolone, a synthetic adrenal cortical hormone, on the urinary excretion of nicotinamide and such catabolic metabolites as N1-methyhiicotinamide (MNA), N1-methyl-2-pyridone-5-carboxamide (2-Py) and N1-methyl-4-pyridone-3-carboxamide (4-Py) were investigated. Rats fed with a niacin-free diet were intraperitoneally injected with prednisolone (3mg/rat) three times at 09:00, 13:00 and 17:00 hr on day 0. As a result, the urinary excretion of nicotinamide, MNA, 2-Py and 4-Py was each higher in the prednisolone group than in the physiological saline group (for control) after 1 day; however, each excretion was lower in the prednisolone group than in control group after 3, 4, 5 and 6 days. On around the 7th day, the urinary excretion in the prednisolone group was restored to the control values. The initial rapid increase and subsequent decrease in the urinary excretion of nicotinamide and its metabolites by an injection of prednisolone is considered to be attributable to a respective elevation of the liver tryptophan oxygenase level and the liver aminocarboxymuconate-semialdehyde decarboxylase level.

Fates of N'-methylnicotinamide and nicotinamide N-oxide in mice.

This experiment was performed to investigate the possibility that N'-methylnicotinamide (N'-methyl-3-pyridinecarboxamide) and nicotinamide N-oxide have niacin activity or not in animals. When 20 mg N'-methylnicotinamide per mouse was administered, urinary excretion of nicotinamide, N1-methylnicotinamide (MNA), N1-methyl-2-pyridone-5-carboxamide (2-Py), and N1-methyMpyridone-3-carboxamide (4-Py) increased 24-, 3-, 3-, and 3-fold, respectively, compared with the control values. The increased ratios of MNA, 2-Py, and 4-Py were almost the same as those when 20 mg nicotinamide was administered. Therefore, the relative activity of N'-methylnicotinamide to nicotinamide as niacin was considered to be about 1. When 20 mg nicotinamide N-oxide per mouse was administered, urinary excretion of nicotinamide, MNA, 2-Py, and 4-Py increased 6.4-, 1.8-, 1.6-, and 1.7-fold, respectively, compared with the control values. The increased ratios of MNA, 2-Py, and 4-Py were about 1/2 of those when 20 mg nicotinamide was administered, so the relative activity of nicotinamide N-oxide to nicotinamide as niacin is considered to be about 1/2. In conclusion, it was found the possibility that the reactions N'-methylnicotinamide→nicotinamide and nicotinamide N-oxide→nicotinamide occur, at least in mice, and that therefore N'-methylnicotinamide and nicotinamide N-oxide have niacin activity.

Changes in Blood NAD and NADP Levels, and the Urinary Excretion of Nicotinamide and Its Metabolites in Women Students after Nicotinamide Administration

Changes in Blood NAD and NADP Levels, and the Urinary Excretion of Nicotinamide and Its Metabolites in Women Students after Nicotinamide Administration

Urinary excretion of nicotinamide and its metabolites in alloxan-diabetic rats fed on a niacin-free diet.

Urinary excretion of nicotinamide and its metabolites in alloxan-diabetic rats fed on a niacin-free diet.

Effect of dietary protein levels on the urinary excretion of nicotinamide and its metabolites in rats.

Male rats of the Wistar strain (seven weeks old) were fed ad libitum with a 10%, 20% or 40% casein diet (these diets contained sufficient nitocinic acid of 6 mg per 100 g of diet) for 20 days. Urine was collected for the last 2 days, and the urinary excretion of nicotinamide, N1-methylnicotinamide (MNA), N1-methyl-2-pyridone-5-carboxamide (2-py) and N1-methy-4-pyridone-3-carboxamide (4-py) was measured using the most reliable determination methods with a high-performance liquid chromatograph. The urinary excretion of nicotinamide and 2-py was about the same in the three groups. The urinary excretion of 4-py increased with increasing dietary protein levels, contrary to MNA, which decreased with increasing dietary protein levels. The total urinary excretion of nicotinamide, MNA, 2-py and 4-py was about the same amount in the three groups. The contents of total nicotinamide and MNA in the liver decreased with increasing dietary protein levels, all these results being inconsistent with the established theory.

Fluorometric determination of nicotinamide and N'-methylnicotinamide and theri urinary excretion in man.

Investigation was made on the fluorometric determination of nicotinamide and N1-methylnicotinamide using column chromatography of ion exchange resins according to Kato. The urinary excretion of nicotinamide and N1-methylnicotinamide was estimated by this improved method in the 24-hour urines of healthy and diabetic subjects.