Thesis (Ph. D.)--University of Wisconsin--Madison, 1984. / Typescript. Vita. eContent provider-neutral record in process. Description based on print version record. Includes bibliographical references (leaves 347-362).

Inaug.-Diss.--Bonn.

The main problem of estrogen metabolism studied has been to determine the nature of the water-soluble products formed from estrone-16-C¹⁴ by rat liver preparations. Comparative studies were carried out in the guinea pig. Three types of water-soluble metabolites were demonstrated, namely, protein-bound derivatives, glucosiduronate conjugates, and unidentified products which were not bound to protein and were not hydrolysed by 2N HC1. The water-soluble metabolites formed on incubating rat or guinea pig liver microsomes with estrone-16-C¹⁴ in the presence of NADPH and oxygen consisted of protein-bound material, some unknown derivatives, but virtually no simple conjugates. Incubation with the rat liver 8000 x g supernatant fraction resulted largely in conversion of the estrogen to the unknown water-soluble end-products, while in contrast, this liver fraction from guinea pig gave rise mainly to glucosiduronates. In the presence of UDPGA, both rat and guinea pig liver microsomes converted estrone-16-C¹⁴ to glucosiduronate conjugates, but this did not occur with the rat liver 8000 x g supernatant fraction. Estradiol-17β-16-C¹⁴and stilbestrol-C¹⁴ behaved similarly to estrone-16-C¹⁴. In the rat, in vivo, the bulk of the urinary water-soluble derivatives of estrone were of unknown nature, while in the guinea pig, glucosiduronate conjugation predominated. The problem was also studied by a different approach. Various compounds having structural features similar to estrone were tested for their ability to inhibit the formation of water-soluble metabolites from this estrogen by rat liver microsomes. It was found that 2-hydroxyestrone, 2-hydroxyestradiol-17β and equilenin were potent inhibitors, while those estrogens which had an oxygen function at C-6 or C-16, as well as the 17β-glucosiduronates and non-phenolic steroids tested were inactive. The synthetic estrogens, stilbestrol and hexestrol, both inhibited the reaction, but their non-estrogenic analogues had no effect. A group of benzoquinones, naphthoquinones and ortho- and para-hydroxylated phenols proved to be powerful inhibitors, whereas anthraquinones and meta-hydroxy-lated phenols showed no activity. In kinetic studies, 2-hydroxyestrone, equilenin, and stilbestrol appeared to act as competitive inhibitors, but menadione gave a mixed type of inhibition. / Medicine, Faculty of / Biochemistry and Molecular Biology, Department of / Graduate

Three mycobacterial strains isolated from fish were tested for their ability to metabolize various amines, supplied individually as sources of carbon. A series of six aliphatic and two cyclic amines was used. Growth occurred only in putreseine. The ability to oxidize putrescine was enhanced by growing the cells in the presence of this compound. One mycobacterial strain appeared to possess some ability to oxidize putrescine without pre-exposure to the compound. However, when cells of this strain were examined for the presence of putrescine and related polyamines, no such compounds were detected. In the mycobacterial strains tested, putrescine did not appear to affect the rate of endogenous respiration. Therefore, in reporting oxygen consumption due to putrescine, the endogenous oxygen consumption has been subtracted from the total oxygen uptake. During the oxidation of putrescine, the oxygen uptake curves "broke" at a point corresponding to approximately 43% of the maximum level of oxidation. Thereafter, very small increases in the level of oxidation occurred, so that by the end of the experiment, over 50% of the molecule appeared to be assimilated. Up to 69-76% of the amino-nitrogen of the putrescine molecule was released as ammonia during the reaction, the rest of the nitrogen being assimilated. Measurement of carbon dioxide production using 1,4-C¹⁴ putrescine revealed that under CO₂-free conditions, at least 1.5 μM of carbon dioxide were released per μM of putrescine. When cells were incubated with 1,4-C¹⁴ putrescine, 25% of the radioactivity was assimilated. The remaining radioactivity was liberated as C¹⁴O₂. Chemical fractionation of the cells indicated that fractions containing lipid, nucleic acid and protein were labelled. Cell-free extracts obtained from putrescine-adapted cells contained four enzymes responsible for the conversion of putrescine to succinic acid. The enzymes occurred in the 10,000 X G supernatants of the cell-free extracts and were all active at pH 9.0. Putrescine was oxidatively deaminated to yield Δ' -pyrroline. The latter compound was then oxidized to ɣ-aminobutyric acid by a dehydrogenase enzyme requiring NAD or NADP. Gamma-aminobutyric acid underwent a transamination with α-ketoglutaric acid to yield succinic semialdehyde and glutamic acid. Succinic semialdehyde was oxidized to succinic acid by an NAD- or NADP- requiring dehydrogenase. The specificity for putrescine, shown by the tested mycobacterial strains, is discussed. / Science, Faculty of / Microbiology and Immunology, Department of / Graduate

[No abstract submitted] / Science, Faculty of / Chemistry, Department of / Graduate

The endocrine in general for a considerable period have been known to exert a humoraal action on the body, controlling its functions to a large extent. These actions have been closely investigated and a clear correlation between the ductless glands have been shown. The interrelation and dependency of the one upon the other, either by inhibition or by stimulation, contribute towards the finer control of the physiology of the body. The studies recorded here are comprised mainly of the dependency of one gland upon another, the relation the normal gland has to protein metabolism, and the alteration in this protein metabolism brought about by alteration in the normal function of one or other of the ductless glands. These features are demonstrated by observing changes in the elimination of creatinine in urine, for this urinary creatinine is regarded as an index of endogenous protein metabolism, and the amount excreted is remarkably constant from day to day.

No description available.

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Thesis (doctoral)--Ludwig-Maximilians-Universität zu München, 1934.

Thesis (doctoral)--Ludwig-Maximilians-Universität zu München, 1934.