Inhibition of kynureninase (L-kynurenine hydrolase,EC3.7.1.3) by oestrone sulphate: an alternative explanation for abnormal results of tryptophan load tests in women receiving oestrogenic steroids

Abstract

1. A partial purification of kynureninase (L-kynurenine hydrolase,EC3.7.1.3) from rat liver and a total resolution of the apoenzyme have been achieved. The hypothesis that conjugates of oestrogenic steroids compete with pyridoxal phosphate for the cofactor binding site of the enzyme, and so disturb tryptophan metabolism, leading to apparent vitamin B6deficiency, has been tested.2. Kynureninase from rat liver was partially purified, and the cofactor-free apoenzyme was prepared. Oestrone sulphate inhibited the enzyme uncompetitively with respect to pyridoxal phosphate, and competitively with respect to kynurenine, with a mean (±SE) inhibitor constant (Ki) of 82 ± 6 μM.3. The addition of a saturating concentration of pyridoxal phosphate to unfractionated liver homogenates led to an approximately fivefold increase in kynureninase activity, indicating the presence of a relatively large amount of apo-kynureninase in the tissue.4. It is suggested that the abnormal results of tryptophan load tests in women receiving oestrogens are the result of inhibition of kynureninase by oestrogen conjugates, and that there is no evidence for oestrogen-induced vitamin B6deficiency in such cases.