title: Regulation of N-terminus-deleted human tyrosine hydroxylase type 1 by end products of catecholamine biosynthetic pathway.
abstract: The N-terminal 52-, 70-, and 157-amino acids-deleted mutants and wild-type tyrosine hydroxylases were expressed in Escherichia coli and utilized to investigate the roles of the N-terminus in the catecholamine inhibition on enzyme activity. Their lysate's supernatants were used as enzyme samples. Three catecholamines, namely dopamine, norepinephrine, and epinephrine, affected both wild-type and mutant enzymes after preincubation in the mode of mixed inhibition, and the most marked alteration among the kinetic parameters produced by the deletion was the increase in the inhibition constants. The deletions also abolished the catecholamine-induced shift of the pH profile of the enzyme activity toward a more acidic pH optimum. All three mutants responded to catecholamines almost in the same way. These results suggest that the three catecholamine end products exert their inhibition on tyrosine hydroxylase to the same extent and that the N-terminal 52 amino acid residues contain the key sequence in mediating the inhibitory action.
authors.affiliation: Joint Research Division for Therapies against Intractable Diseases, School of Medicine, Fujita Health University, Aichi, Japan.
authors.forename: A
authors.initials: A
authors.lastname: Ota
authors.forename: S
authors.initials: S
authors.lastname: Yoshida
authors.forename: T
authors.initials: T
authors.lastname: Nagatsu
mesh_terms: D002384:Catalysis; D002395:Catecholamines / Q000096:biosynthesis / Q000494:pharmacology*; D003001:Cloning, Molecular; D004298:Dopamine / Q000494:pharmacology; D004837:Epinephrine / Q000494:pharmacology; D004926:Escherichia coli; D017353:Gene Deletion; D006801:Humans; D006863:Hydrogen-Ion Concentration; D016014:Linear Models; D016296:Mutagenesis; D009638:Norepinephrine / Q000494:pharmacology; D011994:Recombinant Proteins / Q000096:biosynthesis; D014446:Tyrosine 3-Monooxygenase / Q000096:biosynthesis / Q000235:genetics*
chemical_list: D002395:Catecholamines; D011994:Recombinant Proteins; D014446:Tyrosine 3-Monooxygenase; D004298:Dopamine; D009638:Norepinephrine; D004837:Epinephrine