Mabrouk, Gehan M. Y. (1996) Hormonal regulation of glycine cleavage enzyme system. Masters thesis, Memorial University of Newfoundland.
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The glycine cleavage enzyme complex is a mitochondrial enzyme that is known to be activated by hormones such as glucagon. The effects of several glucagon-related peptides such as glucagon-like peptide-1 (7-36) amide, oxyntomodulin and glicentin, as well as miniglucagon, on the glycine cleavage system were examined in isolated rat hepatocytes. Oxyntomodulin and glicentin were found to stimulate the glycine cleavage system flux through their interaction with the glucagon receptor. Glucagon-like peptide-1 and miniglucagon had no effect on the glycine cleavage system. -- Although the stimulation of the glycine cleavage system by glucagon has been demonstrated previously, it is not known how the hormonal signal is transmitted to the mitochondria. This question is examined in this thesis. The cell-permeable protein phosphatase inhibitor, okadaic acid, was found to stimulate the flux through the glycine cleavage system. The protein kinase A agonist, Sp-cAMPS was also found to stimulate the glycine cleavage system flux, an effect that was inhibited by the protein kinase A antagonist, Rp-8-Br-cAMPS. These results suggest that protein kinase A dependent phosphorylation of cytosolic protein(s) can affect the glycine cleavage system. The role of intracellular calcium in the regulation of the glycine cleavage system was examined using the calcium-mobilizing hormones, vasopressin and angiotensin II, both of which stimulate the glycine cleavage system. Finally, the role of protein kinase C in the regulation of glycine cleavage system was examined using the phorbol ester, Phorbol 12-myristate 13-acetate (PMA). PMA had no effect on the glycine cleavage system or on the glucagon-stimulated glycine cleavage system flux, which suggests no role for protein kinase C in the activation of the glycine cleavage system.
|Item Type:||Thesis (Masters)|
|Additional Information:||Bibliography: leaves 150-188.|
|Department(s):||Science, Faculty of > Biochemistry|
|Library of Congress Subject Heading:||Glycine--Metabolism; Glucagon|
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