Mechanism-based inhibitors of dopamine β-hydroxylase

Paul F. Fitzpatrick, Joseph J. Villafranca

Research output: Contribution to journalArticlepeer-review

40 Scopus citations

Abstract

The copper-containing monooxygenase dopamine β-hydroxylase catalyzes the hydroxylation of dopamine at the benzylic position to form norepinephrine. Mechanismbased inhibitors for dopamine β-hydroxylase have been used as probes of the mechanism of catalysis. The variety of such inhibitors that have been developed for this enzyme can be divided into three groups: (i) those in which the inactivating species is formed by abstraction of a hydrogen atom to form a radical intermediate; (ii) those in which the inactivating species is formed by abstraction of an electron to form an epoxide-like intermediate; and (iii) those in which the product is the inactivating species. A mechanism consistent with inactivation by all three groups of inhibitors which proposes that hydroxylation of dopamine by dopamine β-hydroxylase involves formation of a benzylic radical has been developed. The benzylic radical is formed by abstraction of a hydrogen atom from the substrate by a high-potential copper-oxygen species.

Original languageEnglish (US)
Pages (from-to)231-250
Number of pages20
JournalArchives of Biochemistry and Biophysics
Volume257
Issue number2
DOIs
StatePublished - Sep 1987
Externally publishedYes

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology

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