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Mechanisms of endogenous nitrosation
C D Leaf1, J S Wishnok, S R Tannenbaum
1Division of Toxicology, Massachusetts Institute of Technology, Cambridge 02139.
Summary
The body forms N-nitroso compounds through various pathways. A mammalian cell pathway, using arginine, contributes significantly to daily endogenous nitrosation.
Area of Science:
- Biochemistry
- Toxicology
- Human Physiology
Background:
- Endogenous N-nitroso compounds form in humans and animals.
- Urinary N-nitrosoproline measures the extent of this process.
- Dietary factors influence N-nitroso compound formation.
Purpose of the Study:
- To explore non-gastric pathways of endogenous nitrosation.
- To investigate mammalian cell-catalyzed nitrosation.
- To quantify the contribution of cellular pathways to nitrosation.
Main Methods:
- Measurement of urinary N-nitrosoproline.
- Identification of precursors for nitrosating agents.
- Estimation of pathway contributions to basal nitrosation.
Main Results:
- Non-gastric nitrosation pathways exist, including bacterial and mammalian cell catalysis.
- Mammalian cell pathways utilize arginine as a precursor.
- Cellular pathways contribute approximately 20 nmol of N-nitrosoproline/day to basal levels.
Conclusions:
- Mammalian cells play a role in endogenous nitrosation.
- Arginine is a key precursor in cellular nitrosation pathways.
- Understanding these pathways is crucial for assessing N-nitroso compound risks.