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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.

As compared to the metabolic inhibitor 2,4-Dinitrophenol, the cytostatic drug Adriamycin influences the isolated embryo ventricular cells of the chicken, thus causing a decrease in the contraction amplitude, an increase in the heart-rate, and the occurrence of "after-contractions". With radioactive measurements it could be demonstrated, that the reason therefore is an increment of Ca2+i. This may be explained by a decreased Ca-uptake by the sarcoplasmic reticulum and the mitochondria. This increment of Ca2+i brought about a change in the action potential and the refractory-period, as well as the occurrence of "'after-contractions" by control of the potassium flux.

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