Intrinsic deuterium isotope effects on benzylic hydroxylation by tyrosine hydroxylase

Patrick A. Frantom, Rongson Pongdee, Gary A. Sulikowski, Paul F. Fitzpatrick

Research output: Contribution to journalArticle

25 Scopus citations

Abstract

Tyrosine hydroxylase (TyrH) is a mononuclear, non-heme iron monooxygenase that catalyzes the pterin-dependent hydroxylation of tyrosine to dihydroxyphenylalanine. When 4-methylphenylalanine is used as a substrate for TyrH, 4-hydroxymethylphenylalanine is one of the amino acid products. To examine the mechanism of benzylic hydroxylation, the products and their isotopic compositions were determined with 4-methylphenylalanines containing a mono-, di-, or trideuterated methyl group as substrates. Intrinsic primary and secondary deuterium isotope effects for benzylic hydroxylation of 9.6 ± 0.9 and 1.21 ± 0.08, respectively, were derived from the data. The magnitudes of these isotope effects are consistent with quantum mechanical tunneling of the hydrogen. The similarity of the effects to those seen for benzylic hydroxylation by other enzymes supports a mechanism where a high valence iron-oxo species, Fe(IV)=O, is the hydroxylating intermediate.

Original languageEnglish (US)
Pages (from-to)4202-4203
Number of pages2
JournalJournal of the American Chemical Society
Volume124
Issue number16
DOIs
StatePublished - Apr 24 2002

ASJC Scopus subject areas

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

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