Biomedical subjects
Publications and source records attributed to G Allegri.
Tryptophan metabolism after load test, along the kynurenine pathway was studied in guinea pigs, before and during the psoralen-induced photodermatitis. This skin injury, during the acute phase, causes a large increase in urinary excretion of total metabolites and a significant increase of liver tryptophan pyrrolase.
The levels of total and free serum tryptophan have been determined in a group of newborn babies at birth, one day later and five days after birth. Total and free tryptophan levels are very high in the umbilical cord at birth, decrease quickly and significantly 24 hours after birth and show a slight, but not significant increase five days after birth. The high tryptophan levels at birth and their decrease in the first day after birth recall previous data on tryptophan metabolism "via" serotonin and "via" nicotinic acid. Since the synthesis of cerebral serotonin depends on the availability of tryptophan, and is thus linked to the level of free tryptophan in blood, these data suggest that synthesis of serotonin as well may be elevated at birth and may reach the values of adult soon afterwards. With respect to the nicotinic acid pathway the high levels of tryptophan in blood may be related to the synthesis of tryptophan pyrrolase, which is present in the liver of newborn babies.
Tryptophan metabolism "via kynurenine" after load of amino-acid has been studied in urine of rats before and after induction of experimental light-conditioned dermatitis with psoralen. Tryptophan load in animals during the acute phase of dermatitis (one day after induction) causes a markedly increased urinary excretion of total metabolites in comparison with that obtained before dermatitis. After six days of dermatitis, when the skin damage was in repair, the excretory values after tryptophan load in rats are only slightly increased indicating that the metabolic disturbance is correlated with the skin damage.
Tryptophan load in guinea pigs after induction of a photodermatitis from psoralen caused marked increase of urinary excretion of total metabolites "via kynurenine" in comparison with that obtained before dermatitis. Xanthurenic acid is the metabolite which showed the most increased levels in urine during dermatitis. This dermatitis from furocoumarin caused an alteration of tryptophan metabolism in guinea pigs as well as rats, but species differences in the excretion of metabolites after amino acid load are observed.
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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.
The kynurenine aminotransferase activity of supernatant and mitochondrial fractions obtained from rat liver and kidney was studied with L-kynurenine and L-3-hydroxykynurenine as substrates. A substrate inhibition with L-kynurenine at concentrations higher than 6-7mM was observed with all four enzyme preparations. This did not happen with L-3-hydroxykynurenine as a substrate. Moreover, the liver mitochondrial enzyme shows a Km for pyridoxal phosphate 2-4 times smaller than the other preparations when assayed with L-3-hydroxykynurenine as a substrate. Therefore, the accumulation of xanthurenic acid and not of kynurenic acid in B6 deficiency could be related both to this high activity of liver mitochondrial kynurenine aminotransferase with L-3-hydroxykynurenine, even at small concentrations of B6, and to substrate inhibition observed with L-kynurenine and not with L-3-hydroxykynurenine.
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The tryptophan metabolism "via" kynurenine was studied in five patients with scleroderma after aminoacid loading. Four of these patients had abnormal tryptophan metabolism, characterized by a large urinary excretion of kynurenine and kynurenic acid in two cases, of kynurenine, 3-hydroxykynurenine and kynurenic acid in one case and of 3-hydroxyanthranilic acid in another case and generally a reduced excretion of xanthurenic acid and its 8-methyl ether in comparison with a group of healthy controls. Only two of the four patients had a normal response to tryptophan loading after pyridoxine administration, while no one of these responded to nicotinamide supplementation. But the simultaneous administration of pyridoxine and nicotinamide to three of these patients normalized the excretory picture after tryptophan loading. This suggested the presence of a combined vitamin deficiency in seleroderma. As four out of five patients showed total excretory values of kynurenine, kynurenic acid and acetylkynurenine higher than that of the controls, the sum of these values might be considered as a characteristic index of scleroderma.
The 24 hours urinary excretion of tryptophan metabolites after an aminoacid loading (50 mg/Kg body-weight) was studied in a group of hyperbilirubinemic infants with or without light exposure treatment, in comparison to normal newborn babies. Kynurenine was the main metabolite in the urine of the control subjects. In the hyperbilirubinemic infants a high urinary excretion of kynurenine and 3-hydroxyanthranilic acid was observed. In the ones treated with phototherapy these two substances were markedly decreased. Besides 3-hydroxykynurenine was almost always absent. The effect of the light exposure was studied on kynurenine and 3-hydroxykynurenine "in vitro". Kynurenine did not present any photodecomposition. On the contrary, 3-hydroxykynurenine was easily decomposed. This fact can explain the decreased excretion of 3-hydroxykynurenine and 3-hydroxyanthranilic acid observed in urine of hyperbilirubinemic newborn infants treated with phototherapy. The decrease of kynurenine in these infants probably is a consequence of the photodecomposition of 3-hydroxykynurenine.
D,L-tryptophan[benzene ring-14C (U)] and D,L-tryptophan (methylene-14C) are incorporated significantly into melanin of Harding-Passey mouse melanoma. D,L-5-hydroxytryptophan (methylene-14C) and 5-hydroxytryptamine-3-14C (serotonin) gave an incorporation of radioactivity into melanin significantly lower than tryptophan. D,L-tyrosine-2-14C was incorporated into melanin as well as tryptophan. Therefore tryptophan must be considered an important precursor in the biogenesis of melanins too.
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Kynureninase (L-kynurenine hydrolase E.C. 3.7.1.3.) was purified about 200 times from rat liver. The purified enzyme catalyzes the L-3-hydroxykynurenine leads to 3-hydroxyanthranilate reaction more favorably than the L-kynurenine leads to anthranilate reaction, with Km values of 1.67 x 10(-6) M for L-3-hydroxykynurenine and of 1.67 x 10(-4) M for L-kynurenine. Besides, this enzyme did not produce 5-hydroxyanthranilate from D,L-5-hydroxykynurenine. Therefore we think it is mainly a 3-hydroxykynureninase regulating the tryptophan degradation towards the formation of nicotinic acid necessary to NAD synthesis, rather than towards the accumulation of anthranilate.
The urinary excretion of tryptophan metabolites was studied in 20 aged subjects (over 70 years) after oral tryptophan loading (100 mg/kg body weight). All the subjects considered showed an abnormal excretion of metabolites with mean values of 24.67% in men and 25.83% in women in comparison to 6.77% in young controls. Among the metabolites the highest excretion was from kynurenine; moreover kynurenic acid and N-alpha-acetylkynurenine were also excreted in signficantly high amounts. The other metabolites too showed increased values. As the abnormal tryptophan metabolism in aging seemed to be in connection with vitamin B6 and nicotinamide, in a group of 7 aged sugjects the urinary excretion of tryptophan metabolites was studied after aminoacid loading with or without simultaneous administration of these two vitamins. The results show that the abnormal excretory pattern is normalized after vitamin administration (from 16.49% to 7.42% total mean metabolite values).
The urinary excretion of the metabolites "via kynurenine" was studied in a group of patients with chronic alcoholism after a L-tryptophan loading (100 mg/kg body-weight) with or without simultaneous administration of vitamin B6 or nicotinamide or both. In these subjects an abnormal tryptophan metabolism was obtained with excretion total mean values of 9 metabolites of 15.34% against 6.86% in healthy controls. The treatment with vitamin B6 or nicotinamide in 5 patients decreased the total average excretion from 14.41% to 9.47% and to 9.92% respectively without normalizing, however, the excretory pattern produced from the aminoacid loading. The simultaneous administration of these two vitamins in 9 chronic alcoholic men corrected completely the metabolic defect (from 15.34% to 6.55%).
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Explore the source record for details and available documents.
Explore the source record for details and available documents.