The influence of sex, age, synthetic oestrogens, progestogens and oral contraceptives on the excretion of urinary tryptophan metabolites.

PIP: The excretion of urinary tryptophan metabolites was studied in normal and postmenopausal women and in women taking norethindrone and ethinyl estradiol, singly and in combination. The results showed that the altered tryptophan metabolism found in the preovulatory phase of the cycle and in postmenopausal women was the result of an interaction between Vitamin-B6 and endogenous sex hormones. During the preovulatory phase, endogenous estradiol disrupted the normal activity of the Vitamin-B6-dependent quinolinic acid decarboxylase, which resulted in the accumulation of bladder carcinogens in urine. During the postovulatory phase, endogenous progesterone and the production of metabolites antagonized this effect. Administration of naturally occurring progesterone and of ethinyl estradiol, alone and in combination with norethindrone, was able to counter the interaction between Vitamin-B6 and endogenous estradiol. It is suggested that the cyclic excretion pattern of endogenous bladder carcinogens in young, nonpregnant women may contribute, in part, to the low incidence of bladder cancer in women.^ieng

Studies with tryptophan metabolites in vitro. Kynurenine metabolism in kidneys of mice infested with Schistosoma mansoni.

The conversion in vitro of kynurenine into kynurenic acid and anthranilic acid in both normal kidneys and those obtained from mice infested with Schistosoma mansoni was investigated. Normal mouse kidneys seem to possess an excess of functional pyridoxal phosphate over those obtained from infested mice. Kynureninase and kynurenine transaminase in the latter kidneys are more easily inhibited by deoxypyridoxal phosphate and tartar emetic, indicating low stores of active pyridoxal phosphate. The possible implication of these findings in relation to the role of the kidneys in producing abnormal patterns of tryptophan metabolism and possibly contributing to the production of bladder tumours in bilharzial patients is discussed.

Studies with tryptophan metabolites in vitro. Kynurenine metabolism in liver homogenates of normal and Schistosoma mansoni-infested mice.

The conversion of kynurenine into kynurenic acid and anthranilic acid in both normal and Schistosoma mansoni-infested mouse liver was investigated. It was found that in the S. mansoni-infested mouse liver there is probably a deficiency of pyridoxal phosphate that resulted in an inhibition of kynurenine transaminase and a low production of kynurenic acid. Deoxypyridoxine and its phosphorylated derivative inhibited kynurenine transaminase in the normal liver in a pattern qualitatively similar to that observed with infested liver. The lowered concentration of pyridoxal phosphate in the infested liver is discussed in view of the possibility of two combined mechanisms: (a) an antimetabolite being secreted by the infesting worms or present in its eggs that partially inhibited the phosphorylation of pyridoxal, and (b) concentration of pyridoxal phosphate by the worms, resulting in a lowered concentration of the cofactor in the host tissue.