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Inhibition of kynureninase (L-kynurenine hydrolase, EC 3.7.1.3) by oestrone sulphate: an alternative explanation for abnormal results of tryptophan load tests in women receiving oestrogenic steroids

Published online by Cambridge University Press:  09 March 2007

David A. Bender  and
David Wynick
David A. Bender
Affiliation:
Courtauld Institute of Biochemistry, The Middlesex Hospital Medical School, LondonW1P 7PN
David Wynick
Affiliation:
Courtauld Institute of Biochemistry, The Middlesex Hospital Medical School, LondonW1P 7PN
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Abstract

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1. A partial purification of kynureninase (L-kynurenine hydrolase, EC 3.7.1.3) 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 B6 deficiency, 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 B6 deficiency in such cases.

Type
Papers of direct relevance to Clinical and Human Nutrition
Information
British Journal of Nutrition , Volume 45 , Issue 2 , March 1981 , pp. 269 - 275
Copyright
Copyright © The Nutrition Society 1981

References

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