Stereoselectivity of the demethylation of nicotine piperidine homologues by Nicotiana plumbaginifolia cell suspension cultures.
The metabolism of (R,S)-N-methylanabasine and (R,S)-N-methylanatabine has been studied in a cell suspension culture of Nicotiana plumbaginifolia. Both substrates are effectively demethylated, anabasine or anatabine, respectively, accumulating in the medium. Similarly, there is strong stereoselectivity for the (R)-isomers of both substrates. The kinetics of metabolism of (R,S)-N-methylanabasine differ significantly from those of nicotine in that no further degradation of the initial demethylation product occurs. (R,S)-N-Methylanatabine, however, shows kinetics closer to those of nicotine, with loss of alkaloid from the system. Further more, (R,S)-N-methylanabasine does not diminish (S)-nicotine demethylation, indicating a lack of competition. However, the metabolism of (S)-nicotine is affected by the presence of (R,S)-N-methylanabasine. Hence, the demethylation of the piperidine homologues of nicotine is seen to be similar but not identical to that of the pyridine analogues. The implications of these different metabolic profiles in relation to the demethylation activity are discussed.
Bartholomeusz
Trixie Ann
TA
Laboratoire de Phytotechnologie, EA 3900, Université de Picardie Jules Verne, Faculté de Pharmacie, 1 rue des Louvels, 80037 Amiens, France.
Molinié
Roland
R
Roscher
Albrecht
A
Felpin
François-Xavier
FX
Gillet
Françoise
F
Lebreton
Jacques
J
Mesnard
François
F
Robins
Richard J
RJ
D000470:Alkaloids / Q000737:chemistry / Q000378:metabolism; D000691:Anabasine / Q000031:analogs & derivatives* / Q000737:chemistry / Q000378:metabolism; D002478:Cells, Cultured; D007700:Kinetics; D008745:Methylation; D015394:Molecular Structure; D009538:Nicotine / Q000031:analogs & derivatives* / Q000378:metabolism*; D011725:Pyridines / Q000737:chemistry / Q000378:metabolism; D014026:Nicotiana / Q000166:cytology* / Q000378:metabolism*
D000470:Alkaloids; D011725:Pyridines; C012737:anatabine; D009538:Nicotine; D000691:Anabasine