title: A new mechanism for regulation of tyrosine 3-monooxygenase by end product and cyclic AMP-dependent protein kinase.
abstract: Tyrosine 3-monooxygenase activity of the crude extract from rat striatum had a sharp pH optimum at pH 5.4 and showed almost no activity at or above pH 7. When the crude extract was partially purified by pH precipitation and chromatography on DEAE-cellulose, the enzyme showed a high activity in the pH range of 5.8 to 7.4. Incubation of the partially purified enzyme with catecholamines such as dopamine, norepinephrine, and epinephrine resulted in a remarkable decrease in the enzyme activity, as assayed at a neutral pH. This suppression of the enzyme activity by catecholamines differed from the well-known feedback inhibition which is competitive with respect to the pterin cofactor; the former occurred at a very much lower concentration of catecholamines even in the presence of a near-saturating concentration of a pterin cofactor, and the former was a time-dependent reaction. The enzyme, the activity of which had been suppressed by the incubation with dopamine, was remarkably activated by the incubation with the catalytic subunit of cyclic AMP-dependent protein kinase in the presence of an ATP-generating system. These results suggest that the activity of tyrosine 3-monooxygenase may be suppressed by its end products in a normal state and it may be stimulated by cyclic AMP-dependent protein kinase as occasion demands.
authors.forename: S
authors.initials: S
authors.lastname: Okuno
authors.forename: H
authors.initials: H
authors.lastname: Fujisawa
mesh_terms: D000818:Animals; D003342:Corpus Striatum / Q000201:enzymology; D004298:Dopamine / Q000494:pharmacology; D004789:Enzyme Activation; D004837:Epinephrine / Q000494:pharmacology; D006863:Hydrogen-Ion Concentration; D007700:Kinetics; D009638:Norepinephrine / Q000494:pharmacology; D011494:Protein Kinases / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism*
chemical_list: D014446:Tyrosine 3-Monooxygenase; D011494:Protein Kinases; D004298:Dopamine; D009638:Norepinephrine; D004837:Epinephrine