Inhibition of tryptophan hydroxylase by food-derived carcinogenic heterocyclic amines, 3-amino-1-methyl-5H-pyrido[4,3-b]indole and 3-amino-1,4-dimethyl-5H-pyrido[4,3-b]indole.
Food-derived and carcinogenic heterocyclic amines, 3-amino-1-methyl-5H-pyrido[4,3-b]indole (Trp-P-2) and 3-amino-1,4-dimethyl-5H-pyrido[4,3-b]indole (Trp-P-1), were found to inhibit the activity of tryptophan hydroxylase (TPH) prepared from serotonin-producing murine mastocytomas, P-815 cells. Inhibition of TPH by Trp-P-2 was found to be competitive with the substrate L-tryptophan and non-competitive with the cofactor (6R)-L-erythro-5,6,7, 8-tetrahydrobiopterin. The inhibition proved to be reversible; by dialyzing the sample incubated with Trp-P-2, the enzyme activity could be fully recovered. Among a series of heterocyclic amines examined, Trp-P-1, Trp-P-2 and some other heterocyclic amines inhibited TPH activity. Trp-P-2 and other heterocyclic amines were the newly discovered naturally occurring inhibitors of the indoleamine metabolism.
Naoi
M
M
Department of Biochemistry, Nagoya University School of Medicine, Japan.
Hosoda
S
S
Ota
M
M
Takahashi
T
T
Nagatsu
T
T
D000818:Animals; D001894:Borohydrides; D002243:Carbolines / Q000494:pharmacology*; D002273:Carcinogens / Q000494:pharmacology*; D005504:Food Analysis; D007700:Kinetics; D051379:Mice; D014365:Tryptophan Hydroxylase / Q000037:antagonists & inhibitors*; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000201:enzymology
D001894:Borohydrides; D002243:Carbolines; D002273:Carcinogens; C019133:3-amino-1-methyl-5H-pyrido(4,3-b)indole; D014365:Tryptophan Hydroxylase; C019132:3-amino-1,4-dimethyl-5H-pyrido(4,3-b)indole