Typescript (photocopy) / viii, 197 leaves : ill. ; 30 cm. / Title page, contents and abstract only. The complete thesis in print form is available from the University Library. / Thesis (Ph.D.)--University of Adelaide, Dept. of Pharmacology, 1982

Thesis (Ph. D.)--University of Missouri-Columbia, 2008. / The entire dissertation/thesis text is included in the research.pdf file; the official abstract appears in the short.pdf file (which also appears in the research.pdf); a non-technical general description, or public abstract, appears in the public.pdf file. Vita. "August 2008" Includes bibliographical references.

Thesis (M. Phil.)--University of Hong Kong, 2009. / Includes bibliographical references (leaves 162-171) Also available in print.

Thesis (M.D.)—Boston University

The metabolism of 5'-AMP by 5'-nucleotidase, adenylate deaminase and adenylate kinase was examined in heart homogenates of rat, rabbit, dog, pigeon and turtle. The study was conducted in consideration of the possibility that adenosine, a catabolic product of 5'-AMP, may control vasotone for the autoregulation of coronary blood flow. The relative activities of homogenates of hearts from various species to form adenosine by the action of 5'-nucleotidase generally supported such a role for this nucleoside. Those species anticipated to have the largest potential requirements for coronary vasodilation, i.e. those whose oxygen consumption is known to increase significantly during physical exertion, had the highest levels of cardiac 5'-nucleotidase. An exception to this was the pigeon which had no detectable cardiac 5'-nucleotidase; the order of levels of this enzyme in hearts of the other species tested was: rat > dog > rabbit > turtle. The turtle ventricle, by virtue of its high content of adenylate deaminase and low content of 5'-nucleotidase appeared to catabolize 5'-AMP largely by deamination to IMP. Homogenates of pigeon ventricle contained the greatest activity of adenylate kinase, indicating that the heart of this species is equipped for preservation of ATP by resynthesis from ADP. Enzyme histochemistry revealed that most 5'-nucleotidase of mammalian hearts was localized in the endothelial cells of capillaries. Therefore, if adenosine is involved in regulation of coronary perfusion, its source may be capillary endothelial cells rather than cardiac muscle cells. 5'-Nucleotidase was partially purified from an acetone powder of rat heart. It was active over a broad range of pH with an optimum at pH 8.5. The enzyme was stimulated up to 5-fold by Mg(++) [formula omitted]; Mn(++) and Ni(++) also stimulated activity. The K for 5'-AMP was 2.1 x 10(-5)M in the absence of 16Mg and 2.3 x 10 M in the presence of 16 mM MgCl(2). Certain of its properties indicated that the production of adenosine might be favoured under conditions in which coronary vasodilation would be required and vice-versa. For example, the enzyme was inhibited by ATP, whose levels are greatest in well oxygenated hearts in which energy charge is high. Not all properties of 5'-nucleotidase were consistent with enhanced adenosine formation at reduced energy charge. Both ADP and orthophosphate, the levels of which increase when energy charge decreases, inhibited the enzyme; in fact ADP was a more powerful inhibitor than ATP. In addition, the enzyme was not specific for 5'-AMP but hydrolyzed a variety of nucleoside 5'-monophosphates; and the hydrolysis of 5'-AMP was competitively inhibited by UMP. In the absence of Mg(++) , inhibition by ADP was of the mixed (competitive- non-competitive) type. In the presence of 16 mM MgCl(2), inhibition was non-competitive. On the basis of these data and Dixon plots of inhibition as a function of ADP concentration, it is suggested that two conformations of the enzyme are possible; one which is competitively inhibited by ADP. The simple non-competitive inhibition by ADP, observed in the presence of 16 mM MgCl(2), is attributed to Mg(++) -induced preference for the latter conformation. / Medicine, Faculty of / Anesthesiology, Pharmacology and Therapeutics, Department of / Graduate

No description available.

No description available.

published_or_final_version / abstract / Pharmacology / Doctoral / Doctor of Philosophy

published_or_final_version / Mechanical Engineering / Master / Master of Philosophy

abstract / Medicine / Doctoral / Doctor of Philosophy