Dopamine-B-hydroxylase: suicide inhibition by the novel olefinic substrate, 1-phenyl-1-aminomethylethene.

Abstract

Dopamine-B-hydroxylase [E.C.1.14.17.1] plays a key role in the biosynthetic interconversion of neurotransmitters. It is now demonstrated for the first time that dopamine-B-hydroxylase also catalyzes the oxygenation of an olefinic substrate, 1-phenyl-1-aminomethylethene, producing 2,3-dihydroxy-2-phenylpropylamine after acid workup. This reaction gives the normal oxygenase stoichiometry of electrons to O2 to product of 2:1:1, and is kinetically comparable to other oxygenase activities of dopamine-B-hydroxylase, with a kcat value of 10 sec-1 and a KM of 8.3 mM. 1-Phenyl-1-aminomethylethene is also a time-dependent, first-order inactivator of dopamine-B-hydroxylase. The inactivation process exhibits the characteristics of mechanism-based, irreversible inactivation, giving a KI value of 13 mM and a kinac of 0.04 min-1. The central role of dopamine-B-hydroxylase in catecholamine metabolism suggests possible pharmacological uses for olefinic inhibitors of this enzyme.

• Authors: S W May, P W Mueller, S R Padgette, H H Herman, R S Phillips
• Journal: Biochemical and biophysical research communications (Biochem Biophys Res Commun) Vol. 110 Issue 1 Pg. 161-8 (Jan 14 1983) ISSN: 0006-291X [Print] United States
• PMID: 6860408 (Publication Type: Journal Article, Research Support, U.S. Gov't, Non-P.H.S., Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Phenethylamines
• 1-phenyl-1-aminomethylethene
• Dopamine beta-Hydroxylase

Topics

• Adrenal Glands (enzymology)
• Animals
• Cattle
• Dopamine beta-Hydroxylase (antagonists & inhibitors)
• Kinetics
• Phenethylamines (pharmacology)
• Protein Binding
• Substrate Specificity