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Title: Distribution of, and compounds affecting, the enzymes of cyclic nucleotide metabolism in mammalian tissues
Author: Backer, W. S.
Awarding Body: University of Wales Swansea
Current Institution: Swansea University
Date of Award: 1998
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The physiological role of the cyclic nucleotides, cAMP and cGMP as 'second messengers', prompted this study of the enzymes regulating their concentration in mammalian tissues. The biosynthetic enzymes adenylyl cyclase and guanylyl cyclase were considered as was also the degradative cyclic nucleotide phosphodiesterase. In this present study, the tissues examined were rat kidney, liver, heart and brain. The results indicate that of the tissues examined kidney has the adenylyl cyclase of highest specific activity. The order of adenylyl cyclase specific activity was kidney > heart > brain > liver. Particulate guanylyl cyclase specific activity appeared to be high in liver, but the soluble form predominated in kidney. In contrast to the other tissue examined, brain showed high cAMP and cGMP phosphodiesterases activities. Kinetic properties of adenylyl cyclase and cAMP phosphodiesterase were investigated and the optimum pH was found to be 7.4 for both enzymes. The subcellular fractionation of kidney tissue revealed that both the mitochondrial and microsomal fractions had higher specific activities than did the nuclear fraction. This present study also concerned possible factors causing changes in the activity of adenylyl cyclase in crude extracts of kidney. The effect of the age of the animal, and of presence of metal ions such as Mg2+, Mn2+, Co2+, Fe2+, Zn2+, Ca2+ and Cu2+ were examined. Possible effects of other purine derivatives, including nebularine, Ap3A, and Ap4A were investigated and effects compared to those of forskolin, a known stimulator of adenylyl cyclase activity. A similar study of possible effects of extracts of the medicinal plant Nigella sativa (N.S.) was also made. The results indicate that adenylyl cyclase activity undergoes qualitative changes with age. Mn2+ and Fe2+ had no effect on the activity of adenylyl cyclase at either concentration. Co2+, examined at 1mM concentration only, also activated adenylyl cyclase significantly.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available