Biomaterial Database

[Studies on tryptophan metabolism in untreated phenylketonuric patients]. 1975

W Kochen, and D J Byrd, and R Bühner, and E Bühlen

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.

UI	MeSH Term	Description	Entries
D007736	Kynurenic Acid	A broad-spectrum excitatory amino acid antagonist used as a research tool.	Kynurenate,Acid, Kynurenic
D007737	Kynurenine	A metabolite of the essential amino acid tryptophan metabolized via the tryptophan-kynurenine pathway.
D008297	Male		Males
D009536	Niacinamide	An important compound functioning as a component of the coenzyme NAD. Its primary significance is in the prevention and/or cure of blacktongue and PELLAGRA. Most animals cannot manufacture this compound in amounts sufficient to prevent nutritional deficiency and it therefore must be supplemented through dietary intake.	Nicotinamide,Vitamin B 3,Vitamin PP,3-Pyridinecarboxamide,Enduramide,Nicobion,Nicotinsäureamid Jenapharm,Papulex,Vitamin B3,3 Pyridinecarboxamide,B 3, Vitamin,B3, Vitamin,Jenapharm, Nicotinsäureamid
D009539	Nicotinic Acids	2-, 3-, or 4-Pyridinecarboxylic acids. Pyridine derivatives substituted with a carboxy group at the 2-, 3-, or 4-position. The 3-carboxy derivative (NIACIN) is active as a vitamin.	Acids, Nicotinic
D010649	Phenylalanine	An essential aromatic amino acid that is a precursor of MELANIN; DOPAMINE; noradrenalin (NOREPINEPHRINE), and THYROXINE.	Endorphenyl,L-Phenylalanine,Phenylalanine, L-Isomer,L-Isomer Phenylalanine,Phenylalanine, L Isomer
D010661	Phenylketonurias	A group of autosomal recessive disorders marked by a deficiency of the hepatic enzyme PHENYLALANINE HYDROXYLASE or less frequently by reduced activity of DIHYDROPTERIDINE REDUCTASE (i.e., atypical phenylketonuria). Classical phenylketonuria is caused by a severe deficiency of phenylalanine hydroxylase and presents in infancy with developmental delay; SEIZURES; skin HYPOPIGMENTATION; ECZEMA; and demyelination in the central nervous system. (From Adams et al., Principles of Neurology, 6th ed, p952).	Biopterin Deficiency,Dihydropteridine Reductase Deficiency Disease,Hyperphenylalaninemia, Non-Phenylketonuric,Phenylalanine Hydroxylase Deficiency Disease,BH4 Deficiency,DHPR Deficiency,Deficiency Disease, Dihydropteridine Reductase,Deficiency Disease, Phenylalanine Hydroxylase,Deficiency Disease, Phenylalanine Hydroxylase, Severe,Dihydropteridine Reductase Deficiency,Folling Disease,Folling's Disease,HPABH4C,Hyperphenylalaninaemia,Hyperphenylalaninemia Caused by a Defect in Biopterin Metabolism,Hyperphenylalaninemia, BH4-Deficient, C,Hyperphenylalaninemia, Tetrahydrobiopterin-Deficient, Due To DHPR Deficiency,Non-Phenylketonuric Hyperphenylalaninemia,Oligophrenia Phenylpyruvica,PAH Deficiency,PKU, Atypical,Phenylalanine Hydroxylase Deficiency,Phenylalanine Hydroxylase Deficiency Disease, Severe,Phenylketonuria,Phenylketonuria I,Phenylketonuria II,Phenylketonuria Type 2,Phenylketonuria, Atypical,Phenylketonuria, Classical,QDPR Deficiency,Quinoid Dihydropteridine Reductase Deficiency,Tetrahydrobiopterin Deficiency,Atypical PKU,Atypical Phenylketonuria,Biopterin Deficiencies,Classical Phenylketonuria,Deficiency, BH4,Deficiency, Biopterin,Deficiency, DHPR,Deficiency, Dihydropteridine Reductase,Deficiency, PAH,Deficiency, Phenylalanine Hydroxylase,Deficiency, QDPR,Deficiency, Tetrahydrobiopterin,Disease, Folling,Disease, Folling's,Hyperphenylalaninemia, Non Phenylketonuric,Non Phenylketonuric Hyperphenylalaninemia,Non-Phenylketonuric Hyperphenylalaninemias
D011804	Quinolines
D002648	Child	A person 6 to 12 years of age. An individual 2 to 5 years old is CHILD, PRESCHOOL.	Children
D002675	Child, Preschool	A child between the ages of 2 and 5.	Children, Preschool,Preschool Child,Preschool Children