Sulfestrol

Tyrosine transaminase (L-tyrosine:2-oxoglutarate aminotransferase, EC 2.6.1.5) activity was lost rapidly in fresh rat liver homogenates (pH 6.9) that were incubated at 38°.The inactivation was paralleled by the loss of the coenzyme, but was not reversed by the subsequent addition of pyridoxal 5-phosphate.The coenzyme, the keto acid substrates, and their anionic analogs retarded the inactivation and dissociationVarious anionic steroids and diethylstilbestrol disulfate (5 × 10-4-5 × 10-5M) also retarded the inactivation and dissociation; free steroids were ineffective at saturation levels.Aromatic carboxylic acids were effective at 10-2-10-3M, 5-hydroxytryptophan at 10-3M, and L-glutamate, bicarbonate, and inorganic phosphate at 10-2M.Several other amino acids and NaCl were ineffective at 10-2M.Many of the in vitro stabilizing agents caused elevated levels of hepatic tyrosine transaminase when injected into adrenalectomized rats.In general, the most potent stabilizers were also the most effective agents in causing the elevated enzyme levels in vivo.Estradiol disulfate and diethylstilbestrol disulfate also retarded the inactivation and dissociation that occurred when the homogenates were incubated at 25° in 1.1 or 2.2M urea or when partially purified tyrosine transaminase was incubated with trypsin (EC 3.4.4.4) or chymotrypsin (EC 3.4.4.5).The rate of inactivation in homogenates was not significantly changed by the presence of 0.001M EDTA or mercaptoethanol nor by incubation with alk. phosphatase (EC 3.1.3.1).A small but significantly greater degree of association of the tyrosine transaminase with its coenzyme was found in rat liver homogenates prepared 1 hr. after cortisol administration than in the injected controls that were sacrificed immediately.There was also a significantly slower rate of coenzyme dissociation in the 1-hr. animals.Similar doses of cortisone were ineffective in the latter case.26 references.

In a previous study the administration of benzoate, α-naphthoate, diethylstilbestrol disulfate, and various aromatic carboxylic acids to adrenalectomized rats was shown to increase hepatic tyrosine transaminase (L-tyrosine:2-oxoglutarate aminotransferase, EC 2.6.1.5) levels several fold.The action of benzoate was strongly inhibited by the concurrent administration of puromycin or actinomycin D.In the present study, the administration of actinomycin D strongly inhibited the increase in tyrosine transaminase activity caused by the administration of diethylstilbestrol disulfate or α-naphthoate to adrenalectomized rats.In this respect the effect of these aromatic acids resembles that of the glucocorticoids.To further compare the effects of cortisol and the aromatic acids in vivo, several other systems known to be sensitive to the glucocorticoids were examinedCortisol administration, under the indicated conditions, significantly increased the hepatic levels of glycogen, tryptophan oxygenase (L-tryptophan:oxygen oxidoreductase, EC 1.13.1.12), D-amino acid oxidase (D-amino acid:oxygen oxidoreductase (deaminating), EC 1.4.3.3), and L-threonine dehydratase (L-threonine hydro-lyase (deaminating), EC 4.2.1.16).Under equivalent conditions, doses of diethylstilbestrol disulfate and benzoate that increased hepatic tyrosine transaminase levels had no effect on hepatic glycogen and tryptophan oxygenase levels.Benzoate had no effect on hepatic D-amino acid oxidase levels, but increased L-threonine dehydratase levels.32 references.