Inhibition of tryptophan metabolism by oestrogens in the rat: a factor in the aetiology of pellagra

Abstract

1. The effect of the administration of oestrone sulphate on tryptophan metabolism has been assessed in rats in order to determine whether and to what extent inhibition of tryptophan metabolism by oestrogens may be a factor in the aetiology of pellagra, and might explain the reported twofold excess of females over males in many outbreaks of pellagra.2. Feeding ovariectomized rats for 1 week on a diet containing 15 mg oestrone sulphate/kg led to significant inhibition of kynurenine hydroxylase (EC 1 .14.13.9), kynureninase (EC 3 . 7 . 1 .3) and 3-hydroxyanthranilate oxidase (EC 1 . 13.11 .6). There was also a significant increase in plasma tryptophan, suggesting decreased activity of tryptophan oxygenase (EC 1 .13. 11 . 11). This inhibition of tryptophan metabolism will result in a considerable reduction in the synthesis of the nicotinamide nucleotide coenzymes (NAD and NADP) from tryptophan.3. When ovariectomized rats were maintained for 4 weeks on a diet providing no preformed niacin and only a marginally adequate amount of tryptophan (1030 mg/kg), the addition of oestrone sulphate to the diet led to a significant reduction in the liver content of nicotinamide nucleotides and the urinary excretion of the end-product of NAD metabolism, W-methyl nicotinamide.4. It is suggested that when the diet is only marginally adequate in tryptophan and niacin, inhibition of tryptophan metabolism by endogenous or administered oestrogens may be an additional factor in the development of pellagra.Miller (1978) drew attention to the fact that during the first half of the present century, when pellagra was a major problem of public health nutrition in the United States, there was an approximately twofold excess of females over males in the reported deaths from the disease. Over the four decades from 1920 to 1960 a total of 59391 deaths of women were attributed to pellagra, compared with 28022 deaths of males.Individual reports of outbreaks of pellagra also show an excess of females over males. In the 'epidemic' of pellagra at the Mount Vernon Insane Hospital in Alabama in 1906, only eight of a total of eighty-eight cases were men (Searcy, 1907). Albright (1912) reported on 3 16 cases of pellagra in Tennessee; 2 14 were females and 102 males. Aykroyd et al. (1 935) reported that in four Rumanian villages 79% of pellagra victims were females, and in outbreaks of the disease in Missouri and in Georgia in the USSR 72-73 % of the pellagrins were female. More recently there has been a resurgence of pellagra in Zaire (Ermolieff & Grosshans, 1979); in this outbreak there was no difference between the numbers of females and males under the age of 16 years, but in the range of 18-32 years of age there was a small excess of females over males (forty-six women compared with thirty-nine men). Unfortunately, there is no epidemiological information in Casal's original report of la ma1 de la rosa. He described eleven cases in some detail; six were women and five men (Gonzalez, 1900).A number of factors, especially cultural ones, may be responsi...

Non-nutritional uses of vitamin B6

“…There are derangements of tryptophan metabolism in pregnancy. As discussed earlier, oestrogen metabolites inhibit kynureninase, and Bender & Totoe (1984a) showed that oestrogens lead to reduced activity of kynurenine hydroxylase (EC 1.14.13.9) and hydroxyanthranilate oxidase (EC 1.13.11.6) although the mechanism is unclear. In animals, Van-de-Kamp & Smolen (1995) showed that pregnancy has effects on tryptophan metabolism that are additive to those seen in vitamin B 6 deficiency, and that are resistant to modest supplements of the vitamin.…”

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).…”

Kynurenine hydroxylase: a potential rate-limiting enzyme in tryptophan metabolism

“…The K , for kynurenine of partially purified kynurenine hydroxylase from rat liver is 18 k 6 p~, compared with a steady-state concentration of kynurenine in the liver of 4.9 * 0 . 9 p~, suggesting that under normal conditions the enzyme acts somewhat below its maximum rate, and therefore has some capacity for increased activity as the hepatic concentration of kynurenine increases (Bender & McCreanor, 1982).…”