The in vitro metabolism of 17-hydroxy-11-desoxycorticoserone (Reichstein's compound S).

Thesis (M.A.)--Boston UniversityAlthough it has been known that ∆4-pregnene-17a, 21-diol- 3, 20-dione (Reichstein's compoundS) is an intermediate in the biosynthesis of hydrocortisone (13), little was known of other aspects of its metabolism. The in vitro technique for study was chosen in the hope that the isolation of metabolites would permit an interpretation of the mechanism involved in the metabolism of compoundS. Since it has been demonstrated that liver contains a relatively high concentration of the necessary enzyme systems for the transformation of steroids, preparations of this tissue were selected for this in vitro metabolism study. Compound S was incubated with several types of enzyme preparations of rat liver, and products containing reduced structural configurations involving positions 3 and 5 were isolated. The utilization of silica gel column and paper chromatographic resolution has permitted the purification and resolution of two steroid metabolites in crystalline form. [TRUNCATED

The in vitro metabolism of a typical adrenocortical steroid (11-deoxycortisol)

Thesis (Ph.D.)--Boston UniversityThe liver has been well established as being one of the most important organs involved in the metabolism of adrenocortical steroids. Liver perfusion, incubations with liver slices, homogenates and purified liver preparations all effect extensive changes on the steroid nucleus. In order to develop a step-wise scheme for the in vitro metabolism of a typical adrenocortical steroid and to localize enzyme systems effecting single metabolic transformations, 11-deoxycortisol was incubated with various rat liver homogenate fractions and the conversion products isolated and identified. The liver fractions were obtained by differential centrifugation of liver homogenates. This procedure afforded a 6000 x g supernatant, a 6000 x g residue (corresponding to mitochondria in sedimentation properties), a 78,000 x g residue (corresponding to microsoaes in sedimentation properties) and a 78.000 x g particulate free supernatant. Each tissue preparation was incubated with 11-deoxycortisol at 37° c. for two hours with flasks open to the atmosphere. A tissue to steroid ratio of approximately 1000:1, based on the initial weight of the liver, was employed [TRUNCATED]