title: 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.
mesh_terms: D000311:Adrenal Glands / Q000201:enzymology; D000818:Animals; D002417:Cattle; D004299:Dopamine beta-Hydroxylase / Q000037:antagonists & inhibitors*; D007700:Kinetics; D010627:Phenethylamines / Q000494:pharmacology*; D011485:Protein Binding; D013379:Substrate Specificity
chemical_list: D010627:Phenethylamines; C037366:1-phenyl-1-aminomethylethene; D004299:Dopamine beta-Hydroxylase