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  • Title: Effect of natural oestrogens on tryptophan metabolism: evidence for interference of oestrogens with kynureninase.
    Author: Wolf H, Walter S, Brown RR, Arend RA.
    Journal: Scand J Clin Lab Invest; 1980 Feb; 40(1):15-22. PubMed ID: 7367807.
    Abstract:
    Urinary excretion of metabolites of the tryptophan-nicotinic acid ribonucleotide pathway, urinary excretion of 4-pyridoxic acid and blood concentrations of oestradiol and pyridoxal phosphate were studied in groups of post-menopausal women before or during treatment with natural oestrogens, i.e. oestradiol and oestriol, before and after loading doses of 9800 mumol L-tryptophan or 700 mumol L-kynurenine sulphate. Natural oestrogens induced abnormalities of tryptophan metabolism similar to those induced by synthetic oestrogens, and there was a dose related increase in urinary excretion of metabolites of the tryptophan-nicotinic acid ribonucleotide pathway before the kynureninase step. The increase in urinary excretion of these metabolites also after a loading dose of 700 mumol L-kynurenine indicates an inhibitory effect of oestrogens on kynureninase in vivo. Evidence is presented that this inhibition is an effect mediated through decreased availability of vitamin B6, the coenzyme of kynureninase, although the possibility of a direct effect of oestrogens on kynureninase can not be excluded. 12 healthy postmenopausal women were studied in this project with a 2-fold aim--1) to investigate whether the administration of natural estrogens in physiological doses was able to induce changes in tryptophan metabolism, and 2) to investigate, by means of the kynurenine load test, whether kynureninase activity in vivo is depressed by natural estrogens. The natural estrogens ingested by the subjects were estradiol and estriol, and they were administered before and after loading doses of 9800 mcmol of L-tryptophan or 700 mcmol of L-kynurenine suffate. Then urinary excretion of metabolites of tryptophan-nicotinic acid ribonucleotide pathway, urinary excretion of 4-pyridoxic acid, and blood concentrations of estradiol and pyridoxal phosphate were measured. It was found that natural estrogens induced abnormalities of tryptophan metabolism similar to those induced by synthetic estrogen preparations; in addition, a dose-related increase in urinary excretion of metabolites of the tryptophan-nicotinic acid ribonucleotide pathway before the kynureninase step was noted. An in vivo inhibitory effect of estrogens on kynureninase was indicated by the increase in urinary excretion of these metabolites after a loading dose of 700 mcmol of L-kynurenine. This inhibition may be mediated through decreased availability of vitamin B6, the coenzyme of kynureninase, but that argument does not rule out a direct effect of estrogens on kynureninase.
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