Xanthurenic Acid Excretion Research Articles

Vitamin B-6 Status of Women with a Constant Intake of Vitamin B-6 Changes with Three Levels of Dietary Protein

To determine the effect of varying levels of dietary protein with a constant intake of vitamin B-6 (B-6) on B-6 status, nine women were fed diets providing daily intakes of 1.25 mg B-6 and 0.5, 1.0 and 2.0 g protein/kg body weight. After an 8-d adjustment period, the women consumed each level of dietary protein for 14 d in a Latin-square design. Several direct and indirect B-6 status indicators were measured in blood and urine. Significant differences among protein levels were found for urinary 4-pyridoxic acid (4-PA) excretion (P < 0.01), plasma pyridoxal 5′-phosphate (PLP) concentration (P < 0.05), and urinary excretion of volatile amines (VA, kynurenine plus acetylkynurenine) after a 2-g L-tryptophan load (P < 0.05). Nitrogen intake was significantly negatively correlated with urinary 4-PA excretion (r = -0.619, P < 0.001) and plasma PLP concentration (r = -0.549, P < 0.01), and positively correlated with erythrocyte alanine aminotransferase percentage stimulation (r = 0.418, P < 0.05) and urinary post-tryptophan load excretion of xanthurenic acid (r = 0.535, P < 0.05), kynurenic acid (r = 0.563, P < 0.05) and VA (r = 0.626, P < 0.01). Compared with men consuming diets with similar B-6 to protein ratios in a previous study, the women excreted a greater percentage of the B-6 intake as 4-PA, had lower plasma PLP concentrations and excreted greater amounts of postload urinary tryptophan metabolites at all three protein levels. If the Recommended Dietary Allowance (RDA) of vitamin B-6 is to be based on the dietary B-6 to protein ratio, gender differences in response to varying protein intakes should be considered. For the levels of protein intake used in this study and a B-6 intake of 1.25 mg/d, a B-6 to protein ratio of greater than 0.020 mg/g is required for adequate vitamin B-6 status in women.

A Homozygous Deletion of Exon 5 of KYNU Resulting from a Maternal Chromosome 2 Isodisomy (UPD2) Causes Catel-Manzke-Syndrome/VCRL Syndrome

Vertebral, Cardiac, Renal and Limb Defect Syndrome (VCRL), is a very rare congenital malformation syndrome. Pathogenic variants in HAAO (3-Hydroxyanthranilate 3,4-dioxygenase), NADSYN1 (NAD+ Synthetase-1) and KYNU (Kynureninase) have been identified in a handful of affected individuals. All three genes encode for enzymes essential for the NAD+ de novo synthesis pathway. Using Trio-Exome analysis and CGH array analysis in combination with long range PCR, we have identified a novel homozygous copy number variant (CNV) encompassing exon 5 of KYNU in an individual presenting with overlapping features of VCRL and Catel–Manzke Syndrome. Interestingly, only the mother, not the father carried the small deletion in a heterozygous state. High-resolution SNP array analysis subsequently delineated a maternal isodisomy of chromosome 2 (UPD2). Increased xanthurenic acid excretion in the urine confirmed the genetic diagnosis. Our findings confirm the clinical, genetic and metabolic phenotype of VCRL1, adding a novel functionally tested disease allele. We also describe the first patient with NAD+ deficiency disorder resulting from a UPD. Furthermore, we provide a comprehensive review of the current literature covering the genetic basis and pathomechanisms for VCRL and Catel–Manzke Syndrome, including possible phenotype/genotype correlations as well as genetic causes of hypoplastic left heart syndrome.

Biallelic variants in KYNU cause a multisystemic syndrome with hand hyperphalangism.

Catel-Manzke syndrome is characterized by the combination of Pierre Robin sequence and radial deviation, shortening as well as clinodactyly of the index fingers, due to an accessory ossification center. Mutations in TGDS have been identified as one cause of Catel-Manzke syndrome, but cannot be found as causative in every patient with the clinical diagnosis. We performed a chromosome microarray and/or exome sequencing in three patients with hand hyperphalangism, heart defect, short stature, and mild to severe developmental delay, all of whom were initially given a clinical diagnosis of Catel-Manzke syndrome. In one patient, we detected a large deletion of exons 1-8 and the missense variant c.1282C > T (p.Arg428Trp) in KYNU (NM_003937.2), whereas homozygous missense variants in KYNU were found in the other two patients (c.989G > A (p.Arg330Gln) and c.326G > C (p.Trp109Ser)). Plasma and urine metabolomic analysis of two patients indicated a block along the tryptophan catabolic pathway and urine organic acid analysis showed excretion of xanthurenic acid. Biallelic loss-of-function mutations in KYNU were recently described as a cause of NAD deficiency with vertebral, cardiac, renal and limb defects; however, no hand hyperphalangism was described in those patients, and Catel-Manzke syndrome was not discussed as a differential diagnosis. In conclusion, we present unrelated patients identified with biallelic variants in KYNU leading to kynureninase deficiency and xanthurenic aciduria as a very likely cause of their hyperphalangism, heart defect, short stature, and developmental delay. We suggest performance of urine organic acid analysis in patients with suspected Catel-Manzke syndrome, particularly in those with cardiac or vertebral defects or without mutations in TGDS.

Urinary excretion ratio of xanthurenic acid/kynurenic acid as a functional biomarker of niacin nutritional status.

The present study was conducted to survey functional biomarkers for evaluation of niacin nutritional status. Over 500 enzymes require niacin as a coenzyme. Of these, we chose the tryptophan degradation pathway. To create niacin-deficient animals, quinolinic acid phosphoribosyltransferase-knock out mice were used in the present study because wild type mice can synthesize nicotinamide from tryptophan. When the mice were made niacin-deficient, the urinary excretion of xanthurenic acid (XA) was extremely low compared with control mice; however, it increased according to the recovery of niacin nutritional status. The urinary excretion of kynurenic acid (KA) was the reverse of XA. Kynurenine 3-monooxygenase, which needs NADPH, was thought to be suppressed by niacin deficiency. Thus, we calculated the urinary excretion ratio of XA:KA as a functional biomarker of niacin nutrition. The ratio increased according to recovering niacin nutritional status. Low values equate with low niacin nutritional status.

Histological Changes in Pancreatic Islets of Animals with Experimental Diabetes Caused by Xanthurenic Acid under Condition of Suppression of Its Endogenous Synthesis.

Long-term administration of pyridoxine to rats kept on a diabetogenic diet stimulating endogenous synthesis of xanthurenic acid resulted in minimal glycemia, less pronounced decrease in insulin content in β-cells, and more intensive excretion of xanthurenic acid with urine. Histological changes were observed in 23% pancreatic islets, whereas in rats not treated with pyridoxine, destruction and necrosis of 40-45% β-cells were found in 38% of studied islets.

Pantothenic Acid Deficiency May Increase the Urinary Excretion of 2-Oxo Acids and Nicotinamide Catabolites in Rats

Pantothenic acid (PaA) is involved in the metabolism of amino acids as well as fatty acid. We investigated the systemic metabolism of amino acids in PaA-deficient rats. For this purpose, urine samples were collected and 2-oxo acids and L-tryptophan (L-Trp) and its metabolites including nicotinamide were measured. Group 1 was freely fed a conventional chemically-defined complete diet and used as an ad lib-fed control, which group was used for showing reference values. Group 2 was freely fed the complete diet without PaA (PaA-free diet) and used as a PaA-deficient group. Group 3 was fed the complete diet, but the daily food amount was equal to the amount of the PaA-deficient group and used as a pair-fed control group. All rats were orally administered 100 mg of L-Trp/kg body weight at 09:00 on day 34 of the experiment and the following 24-h urine samples were collected. The urinary excretion of the sum of pyruvic acid and oxaloacetic acid was higher in rats fed the PaA-free diets than in the rats fed pair-fed the complete diet. PaA deficiency elicited the increased urinary excretion of anthranilic acid and kynurenic acid, while the urinary excretion of xanthurenic acid decreased. The urinary excretion of L-Trp itself, 3-hydroxyanthranilic acid, and quinolinic acid revealed no differences between the rats fed the PaA-free and pair-fed the complete diets. PaA deficiency elicited the increased excretion of N(1)-methylnicotinamide, N(1)-methyl-2-pyridone-5-carboxamide, and N(1)-methyl-4-pyridone-3-carboxamide. These findings suggest that PaA deficiency disturbs the amino acid catabolism.

The Vitamin B6 Requirement In Oral Contraceptive Users

Women using oral contraceptives (OCs) have been found to excrete increased amounts of several metabolites arising from tryptophan catabolism, the most pronounced change being in xanthurenic acid and kynurenic acid excretion. The abnormality is largely corrected by the administration of pyridoxine, suggesting an increased need for vitamin B6 in OC users. Although a majority of malnourished and well-nourished women show the abnormality in tryptophan metabolism following OC use, investigators differ in their assessment of vitamin B6 status using other tests. The question of vitamin B6 deficiency in OC users is controversial. 2 types of multiparameter assessment approaches have been used to elucidate the vitamin B6 requirement of OC users. In a study of malnourished India women, it was observed that daily supplements of 10 mg pyridoxine from the day of starting contraception largely prevented the development of the abnormality in tryptophan metabolism. This level of supplementation also prevented the OC-mediated deterioration in vitamin B6 status as determined byerythrocyte aspartate aminotransferase activation. In another type of multiparametric approach Brown et al. and Laklem et al. measured the pyridoxine status of OC users on known intakes of the vitamin in a depletion followed by repletion study. Despite the current controversy, it might be advisable to supplement women using OC with pyridoxine to ensure a daily intake of at least 5 mg vitamin B6.

Xanthurenic aciduria due to a mutation in KYNU encoding kynureninase

Massive urinary excretion of xanthurenic acid, 3-hydroxykynurenine and kynurenine, known as xanthurenic aciduria or hydroxykynureninuria, in a young Somali boy suggested kynureninase deficiency. Mutation analysis of KYNU encoding kynureninase of the index case revealed homozygosity for a c.593 A > G substitution leading to a threonine-to-alanine (T198A) shift. A younger brother was found to have a similar excretion pattern and the same genotype. At present, neither of the two boys has symptoms of niacin deficiency. This is the first report linking xanthurenic aciduria to a mutation in the gene encoding kynureninase.

Pyridoxine supplementation corrects vitamin B6 deficiency but does not improve inflammation in patients with rheumatoid arthritis

Patients with rheumatoid arthritis have subnormal vitamin B6 status, both quantitatively and functionally. Abnormal vitamin B6 status in rheumatoid arthritis has been associated with spontaneous tumor necrosis factor (TNF)-α production and markers of inflammation, including C-reactive protein and erythrocyte sedimentation rate. Impaired vitamin B6 status could be a result of inflammation, and these patients may have higher demand for vitamin B6. The aim of this study was to determine if daily supplementation with 50 mg of pyridoxine for 30 days can correct the static and/or the functional abnormalities of vitamin B6 status seen in patients with rheumatoid arthritis, and further investigate if pyridoxine supplementation has any effects on the pro-inflammatory cytokine TNF-α or IL-6 production of arthritis. This was a double-blinded, placebo-controlled study involving patients with rheumatoid arthritis with plasma pyridoxal 5'-phosphate below the 25th percentile of the Framingham Heart Cohort Study. Vitamin B6 status was assessed via plasma and erythrocyte pyridoxal 5'-phosphate concentrations, the erythrocyte aspartate aminotransferase activity coefficient (αEAST), net homocysteine increase in response to a methionine load test (ΔtHcy), and 24 h urinary xanthurenic acid (XA) excretion in response to a tryptophan load test. Urinary 4-pyridoxic acid (4-PA) was measured to examine the impact of pyridoxine treatment on vitamin B6 excretion in these patients. Pro-inflammatory cytokine (TNF-α and IL-6) production, C-reactive protein levels and the erythrocyte sedimentation rate before and after supplementation were also examined. Pyridoxine supplementation significantly improved plasma and erythrocyte pyridoxal 5'-phosphate concentrations, erythrocyte αEAST, urinary 4-PA, and XA excretion. These improvements were apparent regardless of baseline B6 levels. Pyridoxine supplementation also showed a trend (p < 0.09) towards a reduction in post-methionine load ΔtHcy. Supplementation did not affect pro-inflammatory cytokine production. Although pyridoxine supplementation did not suppress pro-inflammatory cytokine production in patients with rheumatoid arthritis, the suboptimal vitamin B6 status seen in rheumatoid arthritis can be corrected by 50 mg pyridoxine supplementation for 30 days. Data from the present study suggest that patients with rheumatoid arthritis may have higher requirements for vitamin B6 than those in a normal healthy population.

Konjac mannan improves the vitamin B-6 status of rats fed a vitamin B-6-deficient diet.

To investigate how dietary fiber in the diet affects vitamin B-6 nutriture of rats which have been deprived of vitamin B-6, rats were made vitamin B-6-deficient by feeding a vitamin B-6-deficient 70% casein diet. They were fed 2% cellulose powder-based vitamin B-6-deficient diets supplemented with 3% of additional dietary fiber sources (agar, konjac mannan, pectin and cellulose powder) for subsequent 18 days. Vitamin B-6 status was evaluated according to several biological criteria (weight gain, urinary excretion of xanthurenic acid after tryptophan loading, plasma pyridoxal 5'-phosphate, apparent pyridoxal 5'-phosphate-saturation of liver kynureninase, urinary excretion of 4-pyridoxic acid and fecal output of vitamin B-6). Vitamin B-6 status evaluated by these criteria was considerably improved in the konjac mannan-fed group, when compared with the respective data of the vitamin B-6 supplemented group. The relative mean effect of the konjac mannan diet was about 40% of the vitamin B-6 supplemented diet. In conclusion, konjac mannan was effective for improving the vitamin B-6 nutritional state in vitamin B-6-deprived rats.

Changes in vitamin B-6 status indicators of women fed a constant protein diet with varying levels of vitamin B-6

Changes in vitamin B-6 status indicators were evaluated in vitamin B-6-replete subjects. Ten young women consumed diets providing 85 g protein/d and 1.03, 1.33, 1.73, and 2.39 mg vitamin B-6/d for 12 or 15 d during four successive diet periods; in a second study, six women were fed diets providing 85 g protein/d and 0.84, 1.14, and 2.34 mg vitamin B-6/d for 10 or 12 d during three successive diet periods. Vitamin B-6 status indicators showing significant differences among intakes included urinary excretion of 4-pyridoxic acid and total vitamin B-6, pyridoxal 5'-phosphate and total vitamin B-6 in plasma, and xanthurenic acid excretion after a 2-g L-tryptophan load. Significant correlations were found between vitamin B-6 intake and 4-pyridoxic acid, total vitamin B-6, plasma pyridoxal 5'-phosphate, plasma total vitamin B-6, erythrocyte alanine aminotransferase percentage stimulation and postload excretion of xanthurenic acid and volatile amines (kynurenine plus acetylkynurenine). Depending on the indicator, between 20% and 70% of the subjects had inadequate values for 4-pyridoxic acid, total vitamin B-6, plasma pyridoxal 5'-phosphate, and erythrocyte alanine aminotransferase percentage stimulation at a vitamin B-6 intake of 1.33 mg/d (0.016 mg vitamin B-6/g protein). A ratio of dietary vitamin B-6 to protein > 0.016 mg/g is required for adequate vitamin B-6 status in women.

Effect of Casein and Soy Protein Isolate on Vitamin B(6) Nutritional Status in Rats.

Two experiments were conducted to test the effect of casein and soy protein isolate (SPI) on the nutritional status of vitamin B(6) in rats. Adult Long-Evans rats were fed with a casein or SPI diet at a 40% protein level with (control) or without (B(6)-deficient) 7 mg of pyridoxine/kg diet. Vitamin-B(6)-deficient rats were depleted of B(6) with (experiment 1) or without (experiment 2) deoxypyridoxine. In experiment 1, each rat was loaded with 150 mg of DL-tryptophan after 5 weeks of pair feeding. The rats on the vitamin-B(6)-deficient SPI diet (SPI-B(6)) excreted twice the amount of urine xanthurenic acid in 24 h than did the rats on the vitamin-B(6)-deficient casein (casein-B(6)) diet (p < 0.05). In experiment 2, L-tryptophan was loaded in a 20-mg dose at the end of each week. The excretion of xanthurenic acid was higher in the SPI-B(6) group than in the casein-B(6) group over the 5-week period of the experiment (p < 0.05). Erythrocyte transaminase (EGOT and EGPT) activities were lower, while EGOT and EGPT indexes were higher in the SPI-B(6) group than in the casein-B(6) group (p < 0.05). The results suggest that the source of dietary protein significantly influenced the status of B(6) nutrition in these rats. Copyright 1997 S. Karger AG, Basel

Zum einfluss von weizenkleie‐ und grünmehlzulagen auf den vitamin‐B6‐ stoffwechsel von sauen mit suboptimaler vitamin‐B6‐versorgung

Ziel der vorliegenden Untersuchungen war, den Einfluß von “natürlichen Ballaststoffzulagen”; wie Weizenkleie und Grümehl bei suboptimaler Vitamin‐B6‐Versorgung auf Kriterien des Vitamin‐B6‐Stoffwechsels von ausgewachsenen Sauen zu prüfen. Dazu wurden zwei Versuche mit 2 Durchgängen an jeweils 12 ausgewachsenen Sauen (180 kg Lebendmasse) in 3 Gruppen durchgeführt. Die Zulagen betru‐gen im ersten Versuch je Tier und Tag 0 g, 225g und 675 g Weizenkleie und im zweiten Versuch 0 g, 575 g und 1150 g Luzernegrünmehl zu einem Vitamin‐B6‐armen Alleinfutter. Als Kriterien dienten die Vitamin‐B6‐Konzentration und ‐Ausscheidung in Kot und Harn, die Vitamin‐B0‐Bilanz (= Zufuhr ‐ Ausscheidung), die Vitamin‐B6‐Konzentration im Blut, hämatologische Parameter, die Aktivität der erythrozytären Aspartat‐Aminotransferase (EAST) und die Xanthurensäureausscheidung nach Trypto‐phanbelastung. Die Vitamin‐B6‐Konzentration im Kot lag bei 10–12 ug/g DM und wurde weder durch die Art noch durch die Höhe der Ballaststoffzulagen beeinflußt. Die gesamte Vitamin‐B6‐Ausscheidung dagegen wurde durch jede Zulagestufe gesteigert, wobei 60–70% des ausgeschiedenen Vitamin B6 im Kot erschienen. Die fäkale Vitamin‐B6‐Ausscheidung wurde durch die höhere Ballaststoffzulage linear gesteigert. Die bakteriell fermentierbare Substanz aus Weizenkleie und Grunmehl verursachte eine höhere bakterielle Vitamin‐B6‐Synthese als reine Cellulose.

Taurine and kynureninase.

Kynureninase is the most important enzyme in tryptophan metabolism. In the main pathway of tryptophan metabolism, kynureninase forms 3-OH-anthranilic acid from 3-OH-kynurenine. In this reaction vitamin B6 is a co-enzyme. An important relationship between -SH groups and liver kynureninase apoenzyme has been reported by Takeuchi8, 9 and Izuta1. We have experimented on kynureninase and S-involved compounds as follows: (i) Kynureninase activity was inhibited in vitamin B6-deficient rats and in streptozotocin (STZ)-induced diabetic rats; (ii) Following tryptophan administration, in rats given taurine or oysters (rich in taurine), the excretion of xanthurenic acid (an index of vitamin B6 deficiency) decreased compared with an excess methionine-administered group; and (iii) The active center of kynureninase apoenzyme (464 amino acid residues) is located near cysteine.KeywordsPyridoxal PhosphateTryptophan MetabolismXanthurenic AcidInhibit Dopa DecarboxylaseAcid Dietary EnrichmentThese keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

In vivo inhibition of kynurenine aminotransferase activity by isonicotinic acid hydrazide in rats.

It is known that the anti-tuberculosis drug, isonicotinic acid hydrazide (INH), causes pellagra, a niacin deficiency syndrome, and peripheral neuritis in humans. We investigated the effects of INH on the metabolism of tryptophan to niacin in rats fed on a niacin-free diet. 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. The inhibition of kynurenine aminotransferase and the resulting decreased formation of xanthurenic acid generally mean a higher conversion ratio of tryptophan to niacin. However, the conversion ratio was no different between the control and INH groups.

Vitamin B-6 requirements of humans

Vitamin B-6, also referred to as vitamin B 6, is the generic descriptor for all 3-hydroxy-2-methylpyridine derivatives possessing the biological activity of pyridoxine. Convincing evidence of the essentiality of the vitamin was demonstrated when hyperirritability and epileptiform-type seizures were reported in infants fed autoclaved commercial liquid formula low in vitamin B-6; administration of the vitamin corrected these symptoms. Vitamin B-6 status and requirements have been assessed using several methodologies. Dietary assessment usually consists of 24-h recall and/or 2–7-d intake records with nutrient composition being estimated using values given in the US Department of Agriculture's Handbook 8 series. Frequently used biochemical assessment methodologies include xanthurenic acid excretion after a tryptophan load, urinary 4-pyridoxic acid level, urinary and plasma total vitamin B-6 levels, erythrocyte alanine and aspartate aminotransferase activity coefficients, and plasma pyridoxal-5′-phosphate concentration. The most accepted vitamin B-6 status parameter is plasma pyridoxal-5′-phosphate concentration; however, more than one method should be utilized in evaluating status. The minimum vitamin B-6 requirement of men as evaluated by different researchers using various methodologies seems to be about 0.65 to 1.25 mg/d; similar estimates have been made for women. Estimates of vitamin B-6 requirements of pregnant and lactating women range from about 2.1 to 7.6 mg/d; pregnancy may affect many of the parameters utilized for assessing vitamin B-6 status. Controlled feeding studies utilizing infants, children, and adolescents are mainly lacking. Recommended Dietary Allowances (RDAs) for vitamin B-6 have existed since 1968; these RDAs are based primarily on protein intake. A few other countries also have recommended intake values for the vitamin. Vitamin B-6 metabolism and requirements may be altered in several diseases and pathological conditions. The symptoms for some but not all patients with these diseases/conditions have been reported to improve when therapeutic doses of the vitamin are given. Vitamin B-6 has been shown to be toxic. Dosages above 200 mg pyridoxine hydrochloride/d are not recommended.

Alteration of MICE L-tryptophan metabolism by the organophosphorous acid triester diazinon

Diazinon [ O, O-diethyl O-(2-isopropyl-6-methyl-4-pyrimidinyl) phosphorothioate] altered the formation of several l-tryptophan metabolites associated with the l-kynurenine pathway in mice. Liver kynurenine formamidase was inhibited almost completely by diazinon (10 mg/kg). The enzyme inhibition resulted in reduced l-kynurenine biosynthesis in livers with a concomitant accumulation of N- formyl- l- kynurenine . In contrast to the liver, plasma l-kynurenine increased up to 5-fold in diazinon-treated mice. Consequently, the urinary excretion of xanthurenic acid and kynurenic add was raised 5- to 15-fold. The revelation of this novel mechanism of diazinon action is an important piece of information needed for a better understanding of the noncholinergic toxicity of organophosphorous add triesters and methylcarbamates.

Difference in Tryptophan-nicotinamide Conversion According to Dietary Nitrogen Sources; Casein, Casein Hydrolysate, and Mixtures of Amino Acids.

We investigated whether the fate of tryptophan (Trp) to nicotinamide (Nam) is changeable according to nitrogen sources or not. Male rats were fed with a nicotinic acid-free diet (Trp content was arranged at about 234mg/100g of diet) containing casein, casein hydrolysates, or mixtures of amino acids (simulating the amino acid pattern of casein) for 12 days. From the urinary excretion of Nam and its metabolites, the conversion ratio was calculated. The conversion ratio was lower in the groups fed with the casein hydrolysate diets than in the groups fed with the casein and amino acid diets. In order to find the reason, the urinary excretion of kynurenic acid, xanthurenic acid, anthranilic acid, and 3-hydroxyanthranilic acid from the upper part of the Trp-Nam conversion pathway, the contents of free Trp in whole blood, and eight kinds of enzyme activities involved in the Trp-Nam pathway were measured. From these results, it is considered that the reason why the conversion ratio was lower in the casein hydrolysate group is due to the lower concentration of free Trp in whole blood and the higher activity of aminocarboxymuconate-semialdehyde decarboxylase. As is known that this enzyme activity is induced by adrenal cortical hormone, it was suggested that the release of this hormone is stimulated by feeding the casein hydrolysate diet.

Effects of Peroxidation Products of Linoleic Acid on Tryptophan–nicotinamide Metabolism in Rats

The flavin and pyridine nucleotide coenzymes are involved in the detoxication of autoxidation products of lipids. In tryptophan-nicotinamide metabolism, kynurenine 3-hydroxylase and N1-methylnicotinamide (MNA) oxidase contain FAD as a coenzyme. So, the effects of dietary autoxidation products of linoleic acid on the metabolism of tryptophan-nicotinamide were investigated using rats. The administration of linoleic acid hydroperoxides or secondary products reduced the urinary excretion of xanthurenic acid, nicotinamide and its metabolites such as MNA, N1-methyl-2-pyridone-5-carboxamide (2-Py), and N1-methyl-4-pyridone-3-carboxamide (4-Py) as compared with the group administered saline or linoleic acid. Among the enzyme activities involved in the tryptophan-nicotinamide metabolism, the activity of NAD+ synthetase was decreased by the administration of linoleic acid hydroperoxides or secondary products. The activities of tryptophan oxygenase and 4-Py-forming MNA oxidase were also decreased by the administrati...

Insensitivity of the Tryptophan-Load Test to Marginal Vitamin B-6 Intake in Rats

The tryptophan-load test for vitamin B-6 nutritional status was administered to adult female Long-Evans rats fed graded levels of pyridoxine hydrochloride (PN.HCl) in two experiments, and its sensitivity to marginal vitamin B-6 intake was evaluated. In Experiment 1, rats were 4-h meal-fed an AIN-76A (20% casein) diet devoid of PN.HCl for 3 wk, then repleted (n = 12) for 6 wk with 4-h pair-fed meals of either 0.25, 0.5, 1.0 or 7.0 (control) mg PN.HCl/kg diet. In Experiment 2, rats (n = 16) were pair-fed for 10 wk either 0.0, 0.5, 1.0 or 7.0 (control) mg PN.HCl/kg diet, with 24-h access to food. Vitamin B-6 nutritional status was assessed at the end of each experiment. Except in rats fed 0 mg PN.HCl/kg diet, mean body weights were not significantly different among diet groups of either experiment. Plasma pyridoxal phosphate (PLP), pyridoxal and total vitamin B-6 concentrations, determined by HPLC, were very sensitive to gradations in dietary PN.HCl concentrations (P less than 0.05). Red blood cell endogenous and PLP-stimulated alanine and aspartate aminotransferase activity did not statistically differentiate all levels of dietary vitamin B-6, although the calculated activity coefficient for each enzyme (stimulated/endogenous activity) did. Urinary xanthurenic acid excretion following a tryptophan load [24.5 mumol (5 mg) L-tryptophan/100 g body weight, injected intraperitoneally] was significantly (P less than 0.05) elevated compared with controls only in the group fed 0 mg PN/HCl/kg diet. At the tryptophan dose used here, the tryptophan-load test was not useful in detecting marginal vitamin B-6 intake in rats.