Urinary anthranilic acid

Urinary anthranilic acid. Higher than normal 48,229... 

Combined Gas Chromatography-Mass Spectrometry in the Determination of Urinary Anthranilic Acid J. Chromatogr. 70(1) 53-57 (1972) ... 

The influence of dose size was also examined in male and female B6C3Fi mice given 0, 10, 100, 1000, 5000, 15 000 or 30 000 ppm (mg/kg diet) ciimamyl anthranilate in the diet for four days (Caldwell et al., 1985). The urinary excretion of cinnamyl anthranilate, hippuric acid and anthranilic acid within 24-h after removal of the test diet rose with increasing cinnamyl anthranilate dose. Cinnamyl anthranilate was detected in increasing quantities in the urine of male mice at 1000 ppm and above. In females, it was only seen at 5000 ppm and above and the levels were two- to nine-fold lower. 

Acetyloxyindole (256), when fed to rats, caused an increase in the urinary excretion of indole, indoxyl sulfate (258), and anthranilic acid, but 1-methoxyindole (257) was almost completely converted to 258 and anthranilic acid, no indole being detected (84MI7). Feeding the rats 1-... 

Boyland and Williams (B18) loaded 10 normal controls with 10 g DL-tryptophan. In spite of the fact that it is essential to use L-tryptophan in studies of this type and although data on excretion of kynurenic and xanthurenic acids are lacking, at least 5% was recovered as increased kynurenine, 3-hydroxykynurenine, anthranilic acid, and 3-hydroxyan-thranilic acid, free and conjugated. It should be pointed out that in these studies only a low percentage of the ingested dose of tryptophan was found in the form of urinary metabolites. The remainder, approximately 93-94%, of the load could not be recovered. 

One of the rare studies of the excretion of tryptophan metabolites, both spontaneous and after load, by patients with hematological disorders, is the work of Altman and Miller (A4). They reported an elevated urinary excretion of anthranilic acid in 9 children with an unusual congenital anemia referred to as erythrogenesis imperfecta (A4). Oral administration of 1.6 g L-tryptophan to one patient led to increased urinary excretion of anthranilic acid as well as other intermediary metabolites of tryptophan. Massive doses of riboflavin per os during 30 days caused no change in the hematological status, but there appeared to be a decrease in the amount of anthranilic acid excreted. 

The investigation of Marver (M2) indicated that the urinary tryptophan metabolites were elevated in 2 children and 3 adults with erythro-genesis imperfecta after a 2-g load of L-tryptophan. Also anthranilic acid was excreted in abnormally large amounts, thus confirming the findings of Altman and Miller (A4). The repeated elevation of urinary tryptophan metabolites after a load dose in the mother of one child with aplastic anemia suggested that the tryptophan abnormality noted in at least this case may be genetically determined. 

The spontaneous urinary pattern during viral hepatitis in an acute phase seems to be abnormal, showing kynurenine in a high percentage of cases together with 3-hydroxykynurenine, 3-hydroxyanthranilic acid, and in a few instances anthranilic acid. Some discrepancies appear for the excretion in clinically recovered subjects, since Quagliariello (Q3) found a normalized output of metabolites, whereas Piazza and Tancredi (P5) found that about 60% showed an abnormal excretion of the same substances. 

Kyrmreninase (EC 3.7.1.3). Failure to convert 3-hy-droxykynurenine to 3-hydroxyanthranilic acid, and kynurenine to anthranilic acid. Increased urinary xanthurenic acid, kynurenine and 3-hydroxykynurenine, especially after ingestion of tryptophan. Some patients mentally retarded, others symptomless. Enzyme may not be absent, but structurally abnormal, with decreased affinity for coenzyme (dietary vitamin Bj temporarily corrects metabolic disturbance, and addition of pyridoxal phosphate to liver biopsy material increases enzyme activity to near normal). See Tryptophan. 

Mefenamic, flufenamic and meclofenamic acids produce renal papillary necrosis in animals (36 ) and the other anthranilic acid analgesics probably have similar effects on the kidney. Urinary symptoms, dysuria, proteinuria and haematuria have been described (20, 86 =). Niflumic acid therapy was asso-dated with greatly increased urinary cell excretion in some patients, while in others there was a significant increase in the blood urea (86 =). 

The metabolism of cinnamyl anthranilate in rats and mice has been studied (Keyhanfar Caldwell, 1996). Male Fischer 344 rats and male CD-I mice were given 250 mg/kg bw [3- C] cinnamyl anthranilate by intraperitoneal injection. The majority of the administered C was excreted in the 0-24-h urine (70% of the dose in rats and 78% in mice). A further 10% (rat) and 6% (mouse) was recovered in the 24-72-h urine with 10% (rat) and 7% (mouse) in the 0-72-h faeces. In the rat, the major urinary metabolite was hippuric acid (95% of urinary C), together with much smaller amounts of benzoic acid. However, in mice, the urine contained relatively less hippuric acid ( 80%) and more benzoic acid (16% of urinary i C), together with 2.2% of the dose as unchanged ciimamyl anthranilate. 

Returning to the major tryptophan catabolic pathway, marked by green arrows in Fig. 25-11, formate is removed hydrolytically (step c) from the product of tryptophan dioxygenase action to form kynurenine, a compound that is acted upon by a number of enzymes. Kynureninase (Eq. 14-35) cleaves the compound to anthranilate and alanine (step d), while transamination leads to the cyclic kynurenic acid (step e). Hie latter is dehydroxylated in an unusual reaction to quinaldic acid, a prominent urinary excretion product. 

Chizhova and Ivanova (C7) studied 20 children, aged 1-12 years, under therapy for leukemia and 10 healthy children as control. A total of 15-20 g of tryptophan was administered during 5-10 days (1.5-3 g/day) to 7 children whereas 13 were given a single dose of 2-3 g. Daily determinations of urinary metabolites by paper chromatography demonstrated a disturbance of tryptophan metabolism in 19 of the 20 leukemic children before and after tryptophan loading. Kynurenine, 3-hydroxykynurenine, and anthranilic and 3-hydroxyanthranilic acids appeared in urine, whereas 5-hydroxyindoleacetic acid was absent in the majority of the young patients. The disturbances of tryptophan metabolism were similar in all of them. Administration of vitamin Be restored tryptophan metabolism to normal in the majority of the patients. 

It has been observed (D6) Aat addition of vitamin Be to insulin therapy allowed the employment of lower doses of insuhn and, in one subject, the total cessation of insulin administration. Finally, Oka and Leppanen (04) studied the tryptophan metabolism in 10 patients with diabetes mellitus and in 12 control subjects by determining the urinary excretion of 5-hydroxyindoleacetic acid, kynurfenine, and anthranilic, 3-hydroxyanthranilic, and xanthurenic acids before and after a load of 2 g L-tryptophan. The authors noted a markedly increased excretion of... 

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