Sanguinarine and chelerythrine as inhibitors of aromatic amino acid decarboxylase.

Quaternary benzo[c]phenanthridine alkaloids sanguinarine, chelerythrine and their dihydroderivatives were tested as inhibitors of aromatic amino acid decarboxylase (EC 4.1, 1.28, AAD) from rat liver. Sanguinarine and chelerythrine exhibited strong inhibition of AAD with Ki 1.2 x 10(-4) M and 5.8 x 10(-4) M, respectively, while no inhibitory effect was observed for their dihydroderivatives. The inhibition was found to be irreversible. The enzyme-inhibitor interaction apparently stabilized AAD against thermal inactivation. Pyridoxal-5'-phosphate partially decreased but did not reverse the inhibition. Dithiothreitol prevented the inhibitory effect of sanguinarine and chelerythrine which indicates that the interaction with thiol groups essential for AAD activity is included in the inhibition mechanism.