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The metabolism and de-bromination of bromotyrosine in vivo

During inflammation, leukocyte-derived eosinophil peroxidase catalyses the formation of hypobromous acid, which can brominate tyrosine residues in proteins to form bromotyrosine. Since eosinophils are involved in the pathogenesis of allergic reactions, such as asthma, urinary bromotyrosine level has...

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Autores principales: Mani, Ali R., Moreno, José C., Visser, Theo J., Moore, Kevin P.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier Science 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4708624/
https://www.ncbi.nlm.nih.gov/pubmed/26638695
http://dx.doi.org/10.1016/j.freeradbiomed.2015.11.030
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author Mani, Ali R.
Moreno, José C.
Visser, Theo J.
Moore, Kevin P.
author_facet Mani, Ali R.
Moreno, José C.
Visser, Theo J.
Moore, Kevin P.
author_sort Mani, Ali R.
collection PubMed
description During inflammation, leukocyte-derived eosinophil peroxidase catalyses the formation of hypobromous acid, which can brominate tyrosine residues in proteins to form bromotyrosine. Since eosinophils are involved in the pathogenesis of allergic reactions, such as asthma, urinary bromotyrosine level has been used for the assessment of children with asthma. However, little is known about the metabolism and disposition of bromotyrosine in vivo. The aim of this study was to identify the major urinary metabolites formed during bromotyrosine metabolism and to develop mass spectrometric methods for their quantitation. Deuterium-labeled bromotyrosine was synthesized by deuterium exchange. [D(3)]bromotyrosine (500 nmole) was injected intraperitoneally into Sprague-Dawley rats and urine was collected for 24 h in a metabolic cage. (13)C-labeled derivatives of bromotyrosine and its major urinary metabolite were synthesized and used as internal standards for quantitation. Following solid phase extraction, urine samples were derivatized to the pentafluorobenzyl ester, and analyzed using isotope dilution gas chromatography and negative-ion chemical ionization mass spectrometry. A novel brominated metabolite, 3-bromo-4-hydroxyphenylacetic acid (bromo-HPA), was identified as the major brominated metabolite of bromotyrosine. Bromo-HPA only accounted for 0.43±0.04% of infused [D(3)]bromotyrosine and 0.12±0.02% of infused [D(3)]bromotyrosine was excreted in the urine unchanged. However, ~1.3% (6.66±1.33 nmole) of infused [D(3)]bromotyrosine was excreted in the urine as the de-brominated metabolite, [D(3)]4-hydroxyphenylacetic acid, which is also a urinary metabolite of tyrosine in mammals. We also tested whether or not iodotyrosine dehalogenase can catalyse de-bromination of bromotyrosine and showed that iodotyrosine dehalogenase is able to de-brominate free bromotyrosine in vitro. We identified bromo-HPA as the main brominated urinary metabolite of bromotyrosine in rats. However, de-halogenation of bromotyrosine is the major metabolic pathway to eliminate free brominated tyrosine in vivo.
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spelling pubmed-47086242016-02-09 The metabolism and de-bromination of bromotyrosine in vivo Mani, Ali R. Moreno, José C. Visser, Theo J. Moore, Kevin P. Free Radic Biol Med Original Contribution During inflammation, leukocyte-derived eosinophil peroxidase catalyses the formation of hypobromous acid, which can brominate tyrosine residues in proteins to form bromotyrosine. Since eosinophils are involved in the pathogenesis of allergic reactions, such as asthma, urinary bromotyrosine level has been used for the assessment of children with asthma. However, little is known about the metabolism and disposition of bromotyrosine in vivo. The aim of this study was to identify the major urinary metabolites formed during bromotyrosine metabolism and to develop mass spectrometric methods for their quantitation. Deuterium-labeled bromotyrosine was synthesized by deuterium exchange. [D(3)]bromotyrosine (500 nmole) was injected intraperitoneally into Sprague-Dawley rats and urine was collected for 24 h in a metabolic cage. (13)C-labeled derivatives of bromotyrosine and its major urinary metabolite were synthesized and used as internal standards for quantitation. Following solid phase extraction, urine samples were derivatized to the pentafluorobenzyl ester, and analyzed using isotope dilution gas chromatography and negative-ion chemical ionization mass spectrometry. A novel brominated metabolite, 3-bromo-4-hydroxyphenylacetic acid (bromo-HPA), was identified as the major brominated metabolite of bromotyrosine. Bromo-HPA only accounted for 0.43±0.04% of infused [D(3)]bromotyrosine and 0.12±0.02% of infused [D(3)]bromotyrosine was excreted in the urine unchanged. However, ~1.3% (6.66±1.33 nmole) of infused [D(3)]bromotyrosine was excreted in the urine as the de-brominated metabolite, [D(3)]4-hydroxyphenylacetic acid, which is also a urinary metabolite of tyrosine in mammals. We also tested whether or not iodotyrosine dehalogenase can catalyse de-bromination of bromotyrosine and showed that iodotyrosine dehalogenase is able to de-brominate free bromotyrosine in vitro. We identified bromo-HPA as the main brominated urinary metabolite of bromotyrosine in rats. However, de-halogenation of bromotyrosine is the major metabolic pathway to eliminate free brominated tyrosine in vivo. Elsevier Science 2016-01 /pmc/articles/PMC4708624/ /pubmed/26638695 http://dx.doi.org/10.1016/j.freeradbiomed.2015.11.030 Text en © 2015 The Authors http://creativecommons.org/licenses/by/4.0/ This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Original Contribution
Mani, Ali R.
Moreno, José C.
Visser, Theo J.
Moore, Kevin P.
The metabolism and de-bromination of bromotyrosine in vivo
title The metabolism and de-bromination of bromotyrosine in vivo
title_full The metabolism and de-bromination of bromotyrosine in vivo
title_fullStr The metabolism and de-bromination of bromotyrosine in vivo
title_full_unstemmed The metabolism and de-bromination of bromotyrosine in vivo
title_short The metabolism and de-bromination of bromotyrosine in vivo
title_sort metabolism and de-bromination of bromotyrosine in vivo
topic Original Contribution
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4708624/
https://www.ncbi.nlm.nih.gov/pubmed/26638695
http://dx.doi.org/10.1016/j.freeradbiomed.2015.11.030
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