Food-derived heterocyclic amines, 3-amino-1,4-dimethyl-5H-pyrido[4,3-b]indole and related amines, as inhibitors of monoamine metabolism.
The effects of heterocyclic amines, pyrolysis products of tryptophan, on monoamine metabolism were examined. Among these amines, 3-amino-1,4-dimethyl-5H-pyrido[4,3-b]indole (Trp-P-1) and 3-amino-1-methyl-5H-pyrido[4,3-b]indole (Trp-P-2) are potent inhibitors of the enzymes related to amine metabolism. They inhibited type A monoamine oxidase more markedly than type B. After culture of a dopamine cell model, clonal pheochromocytoma PC12h cells, with Trp-P-1 activity of tyrosine hydroxylase was decreased by reduction of its affinity to the biopterin cofactor. Trp-P-1 and Trp-P-2 inhibited tryptophan hydroxylase competitively with the substrate and non-competitively with biopterin. These results suggest that food-derived heterocyclic amines may perturb the monoamine levels in the brain through the inhibition of the biosynthesis and metabolism of biogenic amines.
Maruyama
W
W
Department of Neurology, Nagoya University School of Medicine, Japan.
Ota
A
A
Takahashi
A
A
Nagatsu
T
T
Naoi
M
M
D000588:Amines / Q000737:chemistry / Q000494:pharmacology; D000818:Animals; D002243:Carbolines / Q000737:chemistry / Q000494:pharmacology*; D005502:Food; D051379:Mice; D008996:Monoamine Oxidase Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D051381:Rats; D014446:Tyrosine 3-Monooxygenase / Q000037:antagonists & inhibitors
D000588:Amines; D002243:Carbolines; D008996:Monoamine Oxidase Inhibitors; C019133:3-amino-1-methyl-5H-pyrido(4,3-b)indole; D014446:Tyrosine 3-Monooxygenase; C019132:3-amino-1,4-dimethyl-5H-pyrido(4,3-b)indole