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Title page for ETD etd-03302010-122718

Type of Document Dissertation
Author Neill, Meaghan Anne
URN etd-03302010-122718
Title Nitrogen Metabolism: Enzyme Expression and Protein Interactions in the Urea and Nitric Oxide Cycles
Degree PhD
Department Human Genetics
Advisory Committee
Advisor Name Title
Dr. Deborah Murdock Committee Chair
Dr. Doug Mortlock Committee Member
Dr. Marshall Summar Committee Member
Dr. Michael Aschner Committee Member
Dr. Tony Weil Committee Member
  • mRNA expression
  • protein interactions
  • nitric oxide cycle
  • urea cycle
  • protein expression
  • nitrogen metabolism
Date of Defense 2010-03-16
Availability unrestricted
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.

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