Renal N-oxidation of trimethylamine in the chicken during tubular excretion.
Abstract
The Sperber technique of infusion into the renal portal circulation in chickens was used to investigate in vivo the renal tubular transport and renal metabolism of trimethylamine (TMA). When 14C-TMA was infused at a rate of 1 x 10(-9) mol/min the transport efficiency (TE), that is, the tubular excretion of the 14C-label relative to excretion of simultaneously infused paminohippuric acid, was 0.70. Progressive addition of unlabeled TMA up to infusion rates of 1 x 10(-5) mol/min produced a progressive fall in the TE of the 14C-label. Identification of the 14C-label excreted in the urine revealed that approximately 85% of the infused 14C-TMA was excreted by the infused kidney as a single metabolite over the entire range of infusions. By use of the techniques of low-voltage electrophoresis, high-voltage electrophoretic mobility-pH profile, and gas chromatography/mass spectrometry, the renal metabolite was found to be identical with standard 14C-trimethylamine oxide (TMAO). At a TMA infusion rate of 1.5 x 10(-6) mol/kg/min reaching the infused kidney, the rate at which TMAO was formed and excreted by the kidney was 0.12 x 10(-6) mol per g of kidney per min. When 14C-TMAO was infused into chickens its TE was 0.11, which was not evidence for active excretory transport. Infused TMA was almost entirely metabolized in vivo to its N-oxide, TMAO, which then entered the urine. The renal tubular excretion of 14C during infusion of 14C-TMA was inhibited by the cationic blocker of transport, quinine, and by the anionic blocker of transport, probenecid.
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A substantial proportion (40-50%) of individuals with heart failure also demonstrate some extent of kidney dysfunction.
“Importantly, a substantial proportion (40–50%) of individuals with heart failure also demonstrate some extent of kidney dysfunction189,190.”
From Dietary metabolism, the gut microbiome, and heart failure (2019) · cites this paper as [189]
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- Authors
- Acara, M., Camiolo, S., & Rennick, B.
- Venue
- Drug Metabolism and Disposition
- Publisher
- Elsevier BV
- Published
- 1977-01
- Volume
- 5
- Issue
- 1
- Pages
- 82-90
- ISSN
- 0090-9556 (ISSN-L)
- OpenAlex
- W1750597971
- Cited by
- 23
- References
- 0
- Citations by year
- 2022: 1 · 2021: 1 · 2018: 1 · 2017: 2 · 2016: 1 · 2015: 1 · 2014: 1 · 2012: 1
- FWCI
- 0.84
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Drug Metabolism and Disposition (publishedVersion)
- PubMed (publishedVersion)
- PubMed
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Amino Acid Enzymes and Metabolism
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmacology › Pharmacogenetics and Drug Metabolism
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Polyamine Metabolism and Applications
- Keywords
- trimethylamine, trimethylamine N-oxide, renal tubular excretion, renal metabolism, N-oxidation, chicken kidney, transport efficiency, quinine, probenecid
- MeSH terms
- Animals, Biological Transport, Active, Chickens, Chromatography, Gas, Electrophoresis, Paper, Female, Kidney, Kidney Tubules, Methylamines, Oxidation-Reduction, Probenecid, Quinine, Mass Spectrometry, Time Factors
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