Inhibition of human brain aromatic L-amino acid decarboxylase by cooked food-derived 3-amino-1-methyl-5H-pyrido[4,3-b]indole (Trp-P-2) and other heterocyclic amines.

A carcinogenic, food-derived heterocyclic amine, 3-amino-1-methyl-5H-pyrido[4,3-b]indole (Trp-P-2), was found to inhibit aromatic L-amino acid decarboxylase isolated from human brainstem. Trp-P-2 inhibited the enzyme activity toward L-DOPA more markedly than that toward 5-hydroxytryptophan. The inhibition was competitive to a cofactor of the enzyme, pyridoxal-5-phosphate, and the Ki value of Trp-P-2 was 163 microM. The enzyme activity could be fully recovered after removal of Trp-P-2 by gel filtration, which indicates that the inhibition was reversible. Among a series of heterocyclic amines examined for their effects on the activity toward L-DOPA, Trp-P-2 was the most potent inhibitor, followed by 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine, then Trp-P-1. Another heterocyclic amine, 2-amino-3-methyl-9H-pyrido[2,3-b]indole also inhibited the enzyme. The inhibition of the decarboxylase activity by these heterocyclic amines may affect the catecholamine metabolism in human brain.