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In phenylalanine administered rat, tryptophan chiefly metabolized to xanthurenic acid and in nicotinic acid administration to 5-hydroxy indole acetic acid mainly. MAO reaction inhibited by quinoline compound and the inhibition of kynurenine aminotransferase activity through the injection of epinephrine or serotonin were observed. And also the induction of tryptophanpyrrolase in starvation was discussed.

The analysis of the results of a study on the urinary excretion of metabolites "via kynurenine" after the ingestion in man of different amounts of tryptophan is reported. Of the three doses of L-tryptophan administered to the subjects, that is 2 g pro capite, 50 mg/Kg and 75 mg/Kg body weight, it is preferable to choose that of 50 mg/Kg b.w. as a load test. Such a dose assures an excretion of the more important metabolites without significant variations between men and women and without producing overloading effects.

Tryptophan metabolism "via kynurenine" is altered in vitiligo: after a load of the amino acid the urinary excretion of 3-hydroxykynurenine and 3-hydroxyanthranilic acid is decreased, whereas that of xanthurenic acid and its 8-methyl ether is increased. The excretory values of the metabolites suggest a deficiency of the activity of kynurenine hydroxylase and kynunerinase, the enzymes involved in the metabolism of 3-hydroxykynurenine and 3-hydroxyanthranilic acid. The reduced excretion of 3-hydroxykynurenine, a tryptophan metabolite involved in melanin biosynthesis, may indicate a smaller utilization of tryptophan in the biogenesis of the melanins.

With the onset of fever in volunteers exposed to virulent Salmonella typhii as part of a vaccine evaluation study, urinary excretion of kynurenine, acetyl-kynurenine and o-amino-hippurate significantly increased by N-methylnicotinamide decreased. Serum tryptophan concentration at that time was 116% of control in contrast to total serum amino acid values at 83% of control. A 3 gram oral tryptophan load given during illness further increased serum tryptophan concentration to 186% of control and enhanced excretion of the aforementioned catabolites. In addition, urinary anthranilate glucuronide, kynurenate and xanthurenate rose significantly; 3-hydroxykynurenine increased only slightly and N-methyl-nicotinamide was unaltered. Thus, though a tryptophan load aids in detection of alterations in tryptophan catabolism via the kynurenine pathway as a whole, it also distorts the pattern of metabolites detected, seemingly by causing more kynurenine to be shunted to the mitochondria to be acted upon by kynurenine 3-hydroxylase and kynurenine aminotransferase. In unloaded patients the increased urinary excretion of tryptophan metabolites during typhoid fever merely reflect the enhanced flux of amino acids from muscle to liver, akin to that noted in other infections, in excess of that needed for the synthesis of serum proteins or for other metabolic pathways.

High values of anthranilic acid, 3-OH-kynurenine, xanthurenic acid and 3-OH-anthranilic acid are observed in the spontaneous urinary excretion of tryptophan metabolites in girls in the prepubertal age. The highest differences are between the 3-hydroxy metabolites especially the 3-hydroxykynurenine. On the other hand, this metabolic excretion in postmenopausal women is statistically identical to that of women in sexual maturity.

The tryptophan leads to nicotinic acid pathway is inhibited in the nicotinic acid administered rats; in this case tryptophan chiefly metabolizes "via" serotonin. The serotonin pathway is inhibited in the excess phenylalanine administered rats, especially due to the inhibition of the tryptophan-5-hydroxylase reaction. Xanthurenic acid inhibits kynurenine-3-hydroxylase in vitro, which is a very important regulatory enzyme for xanthurenic acid and nicotinic acid production.

A survey was carried out on the techniques developed by numerous research workers in this important field since Liebig discovered the presence of kynurenic acid in the urine of dogs fed on meat and Musajo that of xanthurenic acid in the urine of rats on a fibrin diet. The survey starts with the old methods of assay by precipitation of kynurenic acid and goes on to include the more recent ones of colorimetric assay of xanthurenic acid with ferrous sulphate or ferric chloride and of kynurenic acid by means of transformation into a chloro-derivative of the type of Besthorn dyes. Chromatographic techniques including paper chromatography, thin-layer chromatography, column chromatography nad gas chromatography, enabled researchers to detect the slightest traces of the two quinolincarbonic acids in the biological fluids together with the other metabolites of tryptophan. Among the techniques adopted for this purpose electrophoresis, automatic analyzers, polarography and, finally, the use of labelled substances, in particular L-tryptophan-3-C14, are included.

We have studied tryptophan metabolism "via kynurenine" in women who were oral contraceptives users, living in two different egyptian environments: in the city of Alexandria or in a rural area near Tanta and, in comparison, in control groups of women living in the same environments but who were not contraceptives users. In the non contraceptives users of Tanta we have registered a higher elimination of some metabolites (anthranilic acid, kynurenic acid, xanthurenic acid and 3-OH-anthranilic acid) which might be related to the way of life and environment. The pattern of the kynurenine pathway metabolites of the contraceptives users (studied 1, 3 and 12 months after contraceptives administration) shows some differences with respect to the controls, both in the spontaneous elimination and in that after tryptophan load. These differences are especially evident for anthranilic acid glucuronide, kynurenine and kynurenic, anthranilic and xanthurenic acids. Some differences may be observed after 1 month of contraceptives administration. The effect of tryptophan oral load is superimposed on those of environment and contraceptives use; in the spontaneous elimination of tryptophan metabolites an accomodation to the contraceptives administration is evident. The discrepancies between some of our results and those of the literature might be related to the influence of environmental factors and of the way of life.