Demonstration of a peroxide shunt in the tetrahydropterin-dependent aromatic amino acid monooxygenases

Jorge Alex Pavon, Paul F. Fitzpatrick

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Abstract

The nonheme iron enzyme phenylalanine hydroxylase, tyrosine hydroxylase, and tryptophan hydroxylase catalyze the hydroxylation of their aromatic amino acid substrates using a tetrahydropterin as the source of electrons. The hydroxylating intermediate is proposed to be an Fe(IV)O species. We report here that all three enzymes will catalyze hydroxylation reactions using H 2O 2 in place of tetrahydropterin and oxygen, forming tyrosine and 3-hydroxyphenylalanine from phenylalanine, 4-HOCH 2-phenylalanine from 4-CH 3- phenylalanine, and hydroxycyclohexylalanine from 3-cyclohexylalanine. No peroxide-dependent reaction is seen with active site mutants of TyrH and PheH in which the stability or reactivity of the iron center is compromised. These results provide further support for an Fe(IV)O hydroxylating intermediate.

Original languageEnglish (US)
Pages (from-to)4582-4583
Number of pages2
JournalJournal of the American Chemical Society
Volume131
Issue number13
DOIs
Publication statusPublished - Apr 8 2009

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ASJC Scopus subject areas

  • Catalysis
  • Chemistry(all)
  • Biochemistry
  • Colloid and Surface Chemistry

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