Food-derived hetero-cyclic 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 tryp-tophan, 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.
KeywordsTyrosine Hydroxylase Biogenic Amine Tryptophan Hydroxylase Heterocyclic Amine Oxygen Oxidoreductase
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