rdf-syntax-grammar
mods:
  schema location: http://www.loc.gov/mods/v3 http://www.loc.gov/standards/mods/v3/mods-3-2.xsd
  title info:
    title: Studies of the chemical and regulatory mechanisms of tyrosine hydroxylase
  name:
    name part: Frantom, Patrick Allen
    name part: 1977-
    role:
      role term: creator
  name:
    name part: Fitzpatrick, Paul F.
    role:
      role term: thesis advisor.
  type of resource: text
  genre: bibliography
  origin info:
    place:
      place term: txu
    date issued: 2006
    issuance: monographic
  language:
    language term: eng
  physical description:
    form: electronic
    form: remote
  abstract: Tyrosine hydroxylase (TyrH) catalyzes the pterin-dependent hydroxylation of tyrosine to form dihydroxyphenylalanine. The enzyme requires one atom of ferrous iron for activity. Using deuterated 4-methylphenylalanine substrates, intrinsic primary and secondary isotope effects of 9.6 ± 0.9 and 1.21 ± 0.08 have been determined for benzylic hydroxylation catalyzed by TyrH. The large, normal secondary isotope effect is consistent with a mechanism involving hydrogen atom abstraction to generate a radical intermediate. The similarity of the isotope effects to those measured for benzylic hydroxylation catalyzed by cytochrome P-450 suggests that a high-valent, ferryl-oxo species is the hydroxylating species in TyrH. Uncoupled mutant forms of TyrH have been utilized to unmask isotope effects on steps in the aromatic hydroxylation pathway which also implicate a ferryl-oxo intermediate. Inverse secondary isotope effects were seen when 3,5-²H₂-tyrosine was used as a substrate for several mutant enzyme forms. This result is consistent with a direct attack by a ferryl-oxo species on the aromatic ring of tyrosine forming a cationic intermediate. Rapid-freeze quench Mössbauer studies have provided preliminary spectroscopic evidence for an Fe(IV) intermediate in the reaction catalyzed by TyrH. The role of the iron atom in the regulatory mechanism has also been investigated. The iron atom in TyrH, as isolated, is in the ferric form and must be reduced for activity.The iron can be reduced by a number of one-electron reductants including tetrahydrobiopterin, ascorbate, and glutathione; however, it appears that BH₄ (k[subscript]red = 2.8 ± 0.1 mM⁻¹ s⁻¹) is the most likely candidate for reducing the enzyme in vivo. A one-electron transfer would require a pterin radical. Rapid-freeze quench EPR experiments aimed at detecting the intermediate were unsuccessful, suggesting that it decays very rapidly by reducing another equivalent of enzyme. The active Fe(II) form can also become oxidized by …
  note: by Patrick Allen Frantom.
  note: "Major Subject: Biochemistry"
  note: Title from author supplied metadata (automated record created on Sep. 15, 2006.)
  note: Vita.
  note: Abstract.
  note: Electronic resource.
  note: Mode of access: World Wide Web.
  note: System requirements: World Wide Web access and Adobe Acrobat Reader.
  note: Ph. D. Texas A&M University 2005.
  note: Includes bibliographical references.
  note: Text (Dissertation).
  subject:
    topic: Major biochemistry
  subject:
    topic: kinetic isotope effects
  subject:
    topic: Tyrosine Hydroxylase
  subject:
    topic: mechanism
  identifier: http://hdl.handle.net/1969.1/3817
  record info:
    record content source: TXA
    record creation date: 070131
    record change date: 20151104133915.0
    record identifier: in00002201003