Effect of natural oestrogens on tryptophan metabolism: evidence for interference of oestrogens with kynureninase

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 μmol L-tryptophan or 700 μmol 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 μmol 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.

Key Words:

• kynureninase
• kynurenine
• nicotinic acid
• oestrogens
• pyridoxal phosphate
• tryptophan
• vitamin B₆