Identification of phenylbutyrylglutamine, a new metabolite of phenylbutyrate metabolism in humans

Blandine Comte, Takhar Kasumov, Bradley A. Pierce, Michelle Puchowicz, Mary Ellen Scott, Williams Dahms, Douglas Kerr, Itzhak Nissim, Henri Brunengraber

Research output: Contribution to journalArticle

19 Citations (Scopus)

Abstract

Phenylbutyrate is used in humans for treating inborn errors of ureagenesis, certain forms of cancer, cystic fibrosis and thalassemia. The known metabolism of phenylbutyrate leads to phenylacetylglutamine, which is excreted in urine. We have identified phenylbutyrylglutamine as a new metabolite of phenylbutyrate in human plasma and urine. We describe the synthesis of phenylbutyrylglutamine and its assay by gas chromatography/mass spectrometry as a tert-butyldimethylsilyl or methyl derivative, using standards of [2H5]phenylbutyrylglutamine and phenylpropionylglutamine. After administration of phenylbutyrate to normal humans, the cumulative urinary excretion of phenylacetate, phenylbutyrate, phenylacetylglutamine and phenylbutyrylglutamine amounts to about half of the dose of phenylbutyrate. Thus, additional metabolites of phenylbutyrate are yet to be identified.

Original languageEnglish (US)
Pages (from-to)581-590
Number of pages10
JournalJournal of Mass Spectrometry
Volume37
Issue number6
DOIs
StatePublished - Jul 9 2002

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Phenylbutyrates
Metabolites
Metabolism
Plasma (human)
phenylbutyrylglutamine
Gas chromatography
Mass spectrometry
Assays
Derivatives

All Science Journal Classification (ASJC) codes

  • Spectroscopy

Cite this

Identification of phenylbutyrylglutamine, a new metabolite of phenylbutyrate metabolism in humans. / Comte, Blandine; Kasumov, Takhar; Pierce, Bradley A.; Puchowicz, Michelle; Scott, Mary Ellen; Dahms, Williams; Kerr, Douglas; Nissim, Itzhak; Brunengraber, Henri.

In: Journal of Mass Spectrometry, Vol. 37, No. 6, 09.07.2002, p. 581-590.

Research output: Contribution to journalArticle

Comte, B, Kasumov, T, Pierce, BA, Puchowicz, M, Scott, ME, Dahms, W, Kerr, D, Nissim, I & Brunengraber, H 2002, 'Identification of phenylbutyrylglutamine, a new metabolite of phenylbutyrate metabolism in humans', Journal of Mass Spectrometry, vol. 37, no. 6, pp. 581-590. https://doi.org/10.1002/jms.316
Comte, Blandine ; Kasumov, Takhar ; Pierce, Bradley A. ; Puchowicz, Michelle ; Scott, Mary Ellen ; Dahms, Williams ; Kerr, Douglas ; Nissim, Itzhak ; Brunengraber, Henri. / Identification of phenylbutyrylglutamine, a new metabolite of phenylbutyrate metabolism in humans. In: Journal of Mass Spectrometry. 2002 ; Vol. 37, No. 6. pp. 581-590.
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AU - Kasumov, Takhar

AU - Pierce, Bradley A.

AU - Puchowicz, Michelle

AU - Scott, Mary Ellen

AU - Dahms, Williams

AU - Kerr, Douglas

AU - Nissim, Itzhak

AU - Brunengraber, Henri

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AB - Phenylbutyrate is used in humans for treating inborn errors of ureagenesis, certain forms of cancer, cystic fibrosis and thalassemia. The known metabolism of phenylbutyrate leads to phenylacetylglutamine, which is excreted in urine. We have identified phenylbutyrylglutamine as a new metabolite of phenylbutyrate in human plasma and urine. We describe the synthesis of phenylbutyrylglutamine and its assay by gas chromatography/mass spectrometry as a tert-butyldimethylsilyl or methyl derivative, using standards of [2H5]phenylbutyrylglutamine and phenylpropionylglutamine. After administration of phenylbutyrate to normal humans, the cumulative urinary excretion of phenylacetate, phenylbutyrate, phenylacetylglutamine and phenylbutyrylglutamine amounts to about half of the dose of phenylbutyrate. Thus, additional metabolites of phenylbutyrate are yet to be identified.

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