Reduction of enzymatic activity of tyrosine hydroxylase by a heterocyclic amine, 3-amino-1,4-dimethyl-5H-pyrido(4,3-b)indole (Trp-P-1), was due to reduced affinity to a cofactor biopterin.
A carcinogenic, food-derived heterocyclic amine, 3-amino-1,4-dimethyl-5H-pyrido(4,3-b)indole (Trp-P-1) was found to reduce the enzymatic activity of tyrosine hydroxylase in clonal rat pheochromocytoma PC12h cells, by its supplement to the culture medium. The reduction was observed with 10 microM Trp-P-1, and at this concentration the amount of cell protein and the activity of a non-specific enzyme, beta-galactosidase, were not affected. The mechanism of the reduction of the enzyme activity was clarified by kinetical studies. The amine reduced the affinity of tyrosine hydroxylase to a cofactor, tetrahydrobiopterin. The alteration of the enzymatic properties by Trp-P-1 was discussed in relation to the possible effect on catecholamine metabolism in the brain.
Department of Neurology, Nagoya University School of Medicine, Japan.
W
W
Maruyama
M
M
Minami
A
A
Ota
T
T
Takahashi
A
A
Takahashi
T
T
Nagatsu
M
M
Naoi
D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism; D000310:Adrenal Gland Neoplasms; D000818:Animals; D001708:Biopterins / Q000378:metabolism*; D002243:Carbolines / Q000494:pharmacology*; D002460:Cell Line; D004295:Dihydroxyphenylalanine / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism; D007700:Kinetics; D009153:Mutagens / Q000494:pharmacology*; D010673:Pheochromocytoma; D011485:Protein Binding; D051381:Rats; D014446:Tyrosine 3-Monooxygenase / Q000494:pharmacology*
D002243:Carbolines; D009153:Mutagens; D015102:3,4-Dihydroxyphenylacetic Acid; D001708:Biopterins; D004295:Dihydroxyphenylalanine; D014446:Tyrosine 3-Monooxygenase; C019132:3-amino-1,4-dimethyl-5H-pyrido(4,3-b)indole; D004298:Dopamine