Tryptophan-Stoffwechseluntersuchungen bei unbehandelten Phenylketonurikern

Abstract

Studies on tryptophan metabolism in untreated phenylketonuric patientsThe 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 severely 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 kynurehine, 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 N r methylnicotinamide and Ni-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 this 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 o-aminoacetophenon by mass-spectroscopy. This metabolite is typical for group B. The possible influence of the blood phenylalanine on the metabolism of tryptophan in phenylketonuria is discussed.

“Untypical Aging Off-Flavor” in Wine: Synthesis of Potential Degradation Compounds of Indole-3-acetic Acid and Kynurenine and Their Evaluation as Precursors of 2-Aminoacetophenone

“…A, (2-sulfoindole)-3-acetic acid(14); B, 2,3-dioxindole-3-acetic acid (15); C, 2-(3-indolylmethyl)-indole-3-acetic acid(16).…”

Flavouring Group Evaluation 48: Aminoacetophenone from chemical group 33

“…However, other studies suggest that this substance is produced only in aerobic conditions and the largely anaerobic gut environment would inhibit the production of this substance (Bowden et al, 1976). A study in 10 untreated patients with phenylketonuria showed that 2-aminoacetophenone was excreted as a product of the kynurenine breakdown pathway following tryptophan loading but not following normal dietary intake of tryptophan (Kochen et al, 1975).…”

Xanthurenic Acid Excretion in Urine After Oral Intake of 5 Gram L-Tryptophan by Healthy Volunteers: Standardisation of the Reference Values

“…1) There is no standard method for the determination of xanthurenic acid; some workers use colorimetry (1,7,10), others an array of Chromatographie methods (3,11) or spectrofluorimetry (6).…”

“…2) Some authors have administered L-tiyptophan in a mg/kg body-weight dose (5,6,11) and others in a fixed dose (3,4,7,8,9). Even within each of these administrat ion modes the dose used by different authors was not identical.…”

“…3) Some authors considered the urine collected during 6 hours after Ζ,-tryptophan intake (12), others during 8 hours (4), 12 hours (6) or 24 hours (7,8,9,11).…”