The urea cycle enzymes play an important role in the processing of nitrogen to urea and in producing endogenous nitric oxide by the citrulline-nitric oxide cycle. This project characterizes the expression of urea and nitric oxide cycle enzymes and their intermediates at a cellular level. First, the expression of these enzymes in human tissues is examined. These findings reflect the expression of these genes in the human body at a baseline level. Second, the expression of these enzymes is determined in mouse tissue as well as concentrations of their intermediates (arginine and citrulline) and the end product nitric oxide. Here we discovered that citrulline is correlated with the production of nitric oxide metabolites in mouse tissues. Our third aim involved studying these enzymes in a cell culture environment and exposed to stimuli to measure changes in mRNA expression, protein expression and changes in the concentration of pathway intermediates (arginine and citrulline) as well as the end product nitric oxide. Finally, we examined protein interactions involved in the nitric oxide and urea cycle enzymes.
This work highlights the functional co-localization and interactions of the components and intermediates of the urea and nitric oxide cycles, which has important implications for understanding the molecular biology underlying diseases associated with nitric oxide and urea cycle dysfunction.
| Identifer | oai:union.ndltd.org:VANDERBILT/oai:VANDERBILTETD:etd-03302010-122718 |
| Date | 12 April 2010 |
| Creators | Neill, Meaghan Anne |
| Contributors | Dr. Marshall Summar, Dr. Deborah Murdock, Dr. Doug Mortlock, Dr. Tony Weil, Dr. Michael Aschner |
| Publisher | VANDERBILT |
| Source Sets | Vanderbilt University Theses |
| Language | English |
| Detected Language | English |
| Type | text |
| Format | application/pdf |
| Source | http://etd.library.vanderbilt.edu/available/etd-03302010-122718/ |
| Rights | unrestricted, I hereby certify that, if appropriate, I have obtained and attached hereto a written permission statement from the owner(s) of each third party copyrighted matter to be included in my thesis, dissertation, or project report, allowing distribution as specified below. I certify that the version I submitted is the same as that approved by my advisory committee. I hereby grant to Vanderbilt University or its agents the non-exclusive license to archive and make accessible, under the conditions specified below, my thesis, dissertation, or project report in whole or in part in all forms of media, now or hereafter known. I retain all other ownership rights to the copyright of the thesis, dissertation or project report. I also retain the right to use in future works (such as articles or books) all or part of this thesis, dissertation, or project report. |
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