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.
Ota
M
M
Department of Psychiatry, Nagoya City University School of Medicine, Japan.
Naoi
M
M
Hamanaka
T
T
Nagatsu
T
T
D006916:5-Hydroxytryptophan / Q000378:metabolism; D000588:Amines / Q000494:pharmacology*; D065105:Aromatic Amino Acid Decarboxylase Inhibitors; D001921:Brain / Q000201:enzymology*; D002243:Carbolines / Q000032:analysis / Q000494:pharmacology*; D002273:Carcinogens / Q000032:analysis / Q000494:pharmacology; D003296:Cooking; D004298:Dopamine / Q000378:metabolism; D005504:Food Analysis; D006801:Humans; D007700:Kinetics; D007980:Levodopa / Q000378:metabolism; D010293:Pargyline / Q000494:pharmacology; D011732:Pyridoxal Phosphate / Q000494:pharmacology
D000588:Amines; D065105:Aromatic Amino Acid Decarboxylase Inhibitors; D002243:Carbolines; D002273:Carcinogens; D007980:Levodopa; D011732:Pyridoxal Phosphate; C019133:3-amino-1-methyl-5H-pyrido(4,3-b)indole; D010293:Pargyline; D006916:5-Hydroxytryptophan; D004298:Dopamine