title: [Studies on tryptophan metabolism in untreated phenylketonuric patients].
abstract: The products of the oxidative degradation of tryptophan via the kynurenine pathway were quantitatively determined in the urine of ten untreated patients with phenylketonuria, aged 4--35 years. All the patients were sevrely mentally retarded. The results of the analysis suggest a division of the patients into two groups, A and B. The patients of group A showed a basal urinary excretion of kynurenine, kynurenic acid, 3-hydroxykynurenine and xanthurenic acid which lies in the lower part of the normal range. The increase in excretion of tryptophan metabolites under tryptophan loading was, however, significantly less than in controls. On the average, only 0.63 % of the load was excreted in the form of these assayed metabolites; in contrast, the control value is 1,13 %. In group B, the rate of excretion was higher than normal under basal and loading conditions. The post-tryptophan excretion was four times greater than that of controls (4.64 %). 3-hydroxyanthranilic acid could only be detected in group B after loading. The metabolite 8-hydroxyquinaldic acid, which is supposed to be an abnormal metabolic product of tryptophan, was excreted in milligram amounts. The analysis of the metabolites of 3-hydroxyanthranilic acid showed that the excretion of N1-methylnicotinamide and N1-methyl-2-pyridone-5-carboxamide was within the normal range. The excretion of nicotinic acid and its amide was sporadic in both the patients and controls. Other theoretically possible metabolites in the pathway could not be found. A number of unidentified metabolites could be detected by thin-layer chromatography in the basal state. The excretion of these metabolites was greatly augmented after tryptophan loading. Other substances which were not detectable in the basal state became evident on loading. A number of these metabolites are characteristic either of group A or B. The structural identification of one of the new products has been hindered by its instability. A stable cleavage product was identified as omicron-aminoacetophenon by mass-spectroscopy. This metabolite its typical for group B. The possible influence of the blood phenylalanine on the metabolism of tryptophan in phenylketonuria is discussed.
mesh_terms: D000098:Acetophenones / Q000652:urine; D000293:Adolescent; D000328:Adult; D001711:Biotransformation; D002648:Child; D002675:Child, Preschool; D002852:Chromatography, Ion Exchange; D002855:Chromatography, Thin Layer; D005260:Female; D006801:Humans; D007736:Kynurenic Acid / Q000652:urine; D007737:Kynurenine / Q000031:analogs & derivatives / Q000652:urine; D008297:Male; D013058:Mass Spectrometry; D009536:Niacinamide / Q000652:urine; D009539:Nicotinic Acids / Q000652:urine; D010649:Phenylalanine / Q000097:blood; D010661:Phenylketonurias / Q000378:metabolism* / Q000652:urine; D011804:Quinolines / Q000652:urine; D014364:Tryptophan / Q000378:metabolism*; D014977:Xanthurenates / Q000652:urine; D062367:ortho-Aminobenzoates / Q000652:urine
chemical_list: D000098:Acetophenones; D009539:Nicotinic Acids; D011804:Quinolines; D014977:Xanthurenates; D062367:ortho-Aminobenzoates; D009536:Niacinamide; D007737:Kynurenine; D010649:Phenylalanine; D014364:Tryptophan; D007736:Kynurenic Acid
vernacular_title: Tryptophan-Stoffwechseluntersuchungen bei unbehandelten Phenylketonurikern