Effects of oestradiol and vitamin B₆on tryptophan metabolism in the rat: implications for the interpretation of the tryptophan load test for vitamin B₆nutritional status

Abstract

1. The effects of the administration of oestradiol and vitamin B, on tryptophan metabolism in the rat have been assessed by measurement of the release of 14C0, from [14C]tryptophan, in vivo, in order to determine whether, and to what extent, the abnormalities of tryptophan metabolism that are associated with oestrogen administration can be attributed to drug-induced vitamin B, deficiency or depletion. Two positional isomers of [14qtryptophan have been used; tryptophan as an index of the activity of tryptophan oxygenase (L-tryptophan: oxygen oxidoreductase (decyclizing), EC 1 . 13.11 . 11) and [me~hylene-'~C]trytophan as an index of the activity of kynureninase (L-kynurenine hydrolase, EC 3.7.1 .3).2. The administration of 500 pg oestradiol/kg body-weight led to a reduction in the release of 14C0, from both positional isomers of tryptophan, suggesting that the activities of both tryptophan oxygenase and kynureninase are reduced following oestrogen treatment. The kinetics of the release of 14C0, from [methylene-14C]tryptophan after the administration of oestradiol were compatible with competitive inhibition of kynureninase by oestradiol or a metabolite.3. The administration of 10 mg pyridoxine hydrochloride/kg body-weight also reduced the production of l4COZ from both positional isomers of [14C]tryptophan, suggesting some toxicity of such a high dose of the vitamin. 4.In animals which had received the supplementary dose of vitamin B,, the administration of oestradiol led to further reduction in the production of 14C0, from [ring-2-14C]tryptophan, suggesting a further reduction in the activity of tryptophan oxygenase, and an increase in the production of 14C0, from [methylene-I4C]tryptophan, but with a delay in the peak of production.5. These results confirm that there is no induction of tryptophan oxygenase by oestradiol, but rather reduced activity of the enzyme after the administration of a relatively high dose of the hormone. They also confirm that the inhibition of kynureninase by oestrogen metabolites that has been reported previously in partially-purified enzyme preparations also occurs in vivo. 6. It is suggested that the abnormal results of the tryptophan load test that have been reported in women receiving oestrogens, and which have been interpreted as indicating some extent of drug-induced vitamin B, deficiency, can be accounted for by the inhibition of tryptophan metabolism by oestrogens or their metabolites.Therefore it seems likely that the practice of administering supplements of vitamin B, to women receiving oestrogens may not be appropriate, and indeed may exacerbate the changes in tryptophan metabolism that result from the administration of oestrogens. The tryptophan load test would appear to be unreliable as an index of vitamin B, nutritional status in women receiving oestrogens.The tryptophan load test for vitamin B, nutritional status depends on the fact that kynureninase (L-kynurenine hydrolase, EC 3 . 7 . 1 .3) is a pyridoxal phosphate-dependent enzyme and, in vitamin B, deficiency, the activ...

Research Note: Production Performance of Laying Hens Fed L-Tryptophan

“…However, plasma estradiol levels were not determined in the present study. It has been established that estrogen administration inhibits tryptophan oxigenase (EC 1.13.11.11) and kinureninase (EC 3.7.1.3), which lead to de novo synthesis of nicotinamide in rats (Bender, 1983;Bender and Totoe, 1984).…”

“…al, 1983). Bender and Wynick (1981) and Bender (1983) have shown that the oxidative pathway of tryptophan metabolism is inhibited by estrogen in rats. Recently, it has been suggested that decreased egg production and egg shell quality observed late in the laying year of hens may be related to increased estrogen concentration in the plasma (Edens et al, 1985).…”

High Doses of Vitamin B6 in the Rat Are Associated with Inhibition of Hepatic Tryptophan Metabolism and Increased Uptake of Tryptophan into the Brain

“…Each animal received an intraperitoneal injection of 50 mg L-tryptophan/kg body weight together with a tracer dose of L-[ring-2-I4C]tryptophan (Commissariat d'Energie Atomique, Gif-sur-Yvette, France) at a final specific activity of 0.66 mCi/mmol, at 12.30 h. They were then placed in sealed glass vessels, through which moistened air was passed from a small compressor. The CO, in the exhaled air was collected into Hyamine hydroxide, changed at 10min intervals for 4 h, and radioactivity measured as described previously (Bender, 19830). To ensure that any effects on the production of I4CO2 were due to changes in the metabolism of tryptophan, and not to changes in the metabolism of formate, additional groups of animals received an intraperitoneal injection of 0 .…”

Pyridoxal 5′-Phosphate-Dependent Enzymes at the Crossroads of Host–Microbe Tryptophan Metabolism

“…However, it has been shown that neuronal AADC activity is reduced in the case of vitamin B6 deficiency, either as a consequence of inherited conditions or as a side-effect of pharmacological treatments [ 82 ]. Thus, the decarboxylation step can become limiting under conditions of PLP deficiency in the CNS [ 83 , 84 ]. Whether a similar regulation also occurs at intestinal level remains to be defined.…”