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 journalArticlepeer-review

25 Scopus citations


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
Issue number16
StatePublished - Apr 24 2002

ASJC Scopus subject areas

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


Dive into the research topics of 'Intrinsic deuterium isotope effects on benzylic hydroxylation by tyrosine hydroxylase'. Together they form a unique fingerprint.

Cite this