Hydrazines as inhibitors of dopamine. beta. -hydroxylase

Conference · Thu May 01 04:00:00 EDT 1986 · Fed. Proc., Fed. Am. Soc. Exp. Biol.; (United States)

OSTI ID:5234158

Fitzpatrick, P F; Villafranca, J J

Dopamine ..beta..-hydroxylase (D..beta..H) is inactivated by monosubstituted hydrazines. The initial step in the inactivation is reduction of the enzyme bound copper, forming the hydrazine radical cation. Homolytic cleavage of the hydrazine carbon-nitrogen bond then generates a carbon-centered radical which reacts with the enzyme. Inactivation with (/sup 14/C)-phenylhydrazine results in the incorporation of 0.94 molecules of label per enzyme subunit. Benzylhydrazine behaves as a mechanism-based inhibitor for the enzyme. The second-order rate constant for inactivation of DBETAH by benzylhydrazine in the presence of ascorbate is increased about 4-fold when the benzylic hydrogens are replaced with deuterium. The apparent V/sub max/ shows an observed deuterium kinetic isotope effect of 13 +/- 2. The partition ratio for product formation versus inactivation is 11-fold less for a,a,-d/sub 2/-benzylhydrazine. These results are consistent with a model in which inactivation by benzylhydrazine is due to abstraction of an electron from nitrogen instead of abstraction of a hydrogen atom from the benzylic carbon.

• Research Organization: Pennsylvania State Univ., University Park
• OSTI ID: 5234158
• Report Number(s): CONF-8606151-
• Conference Information: Journal Name: Fed. Proc., Fed. Am. Soc. Exp. Biol.; (United States) Journal Volume: 45:6
• Country of Publication: United States
• Language: English

Related Subjects

550201* -- Biochemistry-- Tracer Techniques
59 BASIC BIOLOGICAL SCIENCES
AMINES
AROMATICS
AUTONOMIC NERVOUS SYSTEM AGENTS
BIOCHEMICAL REACTION KINETICS
CARBON 14 COMPOUNDS
CARDIOTONICS
CARDIOVASCULAR AGENTS
CATIONS
CHARGED PARTICLES
COPPER
DEUTERIUM
DOPAMINE
DRUGS
ELEMENTS
ENZYME ACTIVITY
ENZYME INHIBITORS
ENZYMES
HYDRAZINE
HYDROGEN ISOTOPES
HYDROXY COMPOUNDS
HYDROXYLASES
IONS
ISOTOPE APPLICATIONS
ISOTOPE EFFECTS
ISOTOPES
KINETICS
LABELLED COMPOUNDS
LIGHT NUCLEI
METALS
NEUROREGULATORS
NITROGEN COMPOUNDS
NUCLEI
ODD-ODD NUCLEI
ORGANIC COMPOUNDS
OXIDOREDUCTASES
PHENOLS
POLYPHENOLS
REACTION KINETICS
STABLE ISOTOPES
SYMPATHOMIMETICS
TRACER TECHNIQUES
TRANSITION ELEMENTS