Comparison of coupling subsites and inhibition effects of piperidine alkaloids and aminoketones on plant amine oxidases.
In the present work we compare the binding subsites of inhibitors from a series of alkaloids and aminoketones on pea and sainfoin diamine oxidase (EC 1.4.3.6; DAO) by the graphical method. As standard competitive inhibitors we have chosen oxoanalogs of the substrates, namely, 1,4-diamino-2-butanone and 1,5-diamino-3-pentanone, which were compared with the alkaloids (+)-sedamine, (-)-norallosedamine, (-)-norsedamine, L-lobeline, cinchonine and aromatic analogs of aliphatic aminoketones such as 1-amino-3-phenyl-3-propanone and 1-amino-3-phenyl-2-propanone. In the case of pea DAO all inhibitors compete for the same subsites with 1,4-diamino-2-butanone and 1,5-diamino-3-pentanone (alpha = infinity). In the case of sainfoin enzyme they are bound to other subsites and the interaction constants (0 < alpha < 1) point to a positive attraction between these two types of inhibitors. With sainfoin DAO, 1-amino-3-phenyl-3-propanone is bound into the same subsite as 1,4-diamino-2-butanone. Cinchonine and 1-amino-3-phenyl-3-propanone are bound to two different subsites and the value of the interaction constant (1 < alpha < infinity) shows repulsion between the inhibitors.
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Department of analytical and organic chemistry, Faculty of Science, Palacký University, Olomouc, Czechoslovakia.
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D000470:Alkaloids / Q000494:pharmacology; D006631:Amine Oxidase (Copper-Containing) / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D000588:Amines / Q000494:pharmacology; D001665:Binding Sites; D004305:Dose-Response Relationship, Drug; D007659:Ketones / Q000494:pharmacology; D008956:Models, Chemical; D010880:Piperidines / Q000494:pharmacology; D010944:Plants / Q000201:enzymology*
D000470:Alkaloids; D000588:Amines; D007659:Ketones; D010880:Piperidines; D006631:Amine Oxidase (Copper-Containing)