pH-dependent nitration of para-hydroxyphenylacetic acid in the stomach
Abstract
The major urinary metabolite of nitrotyrosine is 3-nitro-4-hydroxyphenylacetic acid (3-Nitro-HPA). However, recent animal studies have shown that the majority of urinary 3-Nitro-HPA is derived from nitration of endogenous para-hydroxyphenylacetic acid (HPA), a metabolite of tyrosine. One potential site for the formation of 3-Nitro-HPA is the stomach, where nitrous acid is formed by the reaction of nitrite in saliva with gastric acid. The aim of this study was to determine whether there is pH-dependent nitration of salivary para-hydroxyphenylacetic acid or tyrosine, and the effects of dietary nitrate. Healthy volunteers (n = 18) ingested either a low or high nitrate diet, with and without the administration of omeprazole, a proton pump inhibitor. Urinary 3-Nitro-HPA excretion increased from 197 +/- 52 to 319 +/- 88 microg/day on switching from a low to a high nitrate diet (P < 0.05), and decreased (166 +/- 53 mug/day, P < 0.05) when gastric pH was increased by omeprazole. To determine whether 3-Nitro-HPA can be formed by nitration of para-hydroxyphenylacetic acid in the stomach, 500 microg of deuterated para-hydroxyphenylacetic acid was ingested with a high nitrate meal. This led to the excretion of both deuterated HPA and 3-Nitro-HPA in the urine, confirming that para-hydroxyphenylacetic acid is absorbed, and nitrated. Since omeprazole decreases the formation of 3-Nitro-HPA, presumably by decreasing the nitration of endogenous para-hydroxyphenylacetic acid present in saliva, and the observation that ingested deuterated para-hydroxyphenylacetic acid is nitrated and excreted, we conclude that endogenous para-hydroxyphenylacetic acid is nitrated in the stomach, absorbed, and excreted as 3-Nitro-HPA.
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NO2 generation from NO2- occurs in the stomach.
“Also, ⅐ NO 2 generation from NO 2 Ϫ occurs in the stomach (35).”
From Conjugated linoleic acid is a preferential substrate for fatty acid nitration (2012) · cites this paper as [35]
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- Authors
- Pannala, A. S., Mani, A. R., Rice-Evans, C. A., & Moore, K. P.
- Affiliations
- King's College London (GB)
- The Royal Free Hospital (GB)
- Corresponding author
- Moore, Kevin P.
- Venue
- Free Radical Biology and Medicine
- Publisher
- Elsevier BV
- Published
- 2006-09
- Volume
- 41
- Issue
- 6
- Pages
- 896-901
- ISSN
- 0891-5849 (ISSN-L)
- OpenAlex
- W2090077332
- Cited by
- 29
- References
- 13
- Citations by year
- 2022: 2 · 2021: 1 · 2020: 1 · 2019: 1 · 2018: 2 · 2015: 2 · 2013: 3 · 2012: 1
- FWCI
- 1.54
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- Locations
- Free Radical Biology and Medicine (publishedVersion)
- PubMed (publishedVersion)
- UCL Discovery (University College London) (submittedVersion)
- University of Brighton Repository (University of Brighton) (submittedVersion)
- Funders
- Food Standards Agency
- Topics
- Health Sciences › Medicine › Physiology › Nitric Oxide and Endothelin Effects
- Health Sciences › Medicine › Biochemistry › Antioxidant Activity and Oxidative Stress
- Health Sciences › Medicine › Biochemistry › Phytochemicals and Antioxidant Activities
- Keywords
- nitration, stomach, gastric pH, nitrite, dietary nitrate, omeprazole, nitrotyrosine, urinary metabolites, tyrosine metabolism, nitrous acid
- MeSH terms
- Acrylates, Adult, Female, Gastric Mucosa, Humans, Hydrogen-Ion Concentration, Kinetics, Male, Middle Aged, Nitrates, Nitric Oxide, Phenols, Reference Values, Tyrosine
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