Progress in understanding the N-demethylation of alkaloids by exploiting isotopic techniques.
Résumé
The reaction of N-demethylation plays an important role in the degradation of some alkaloids in a number of organisms. This review presents how our understanding of the N-demethylation of nicotine in plants has been improved through studies in cell cultures of Nicotiana plumbaginifolia and N. glutinosa using a variety of isotopic techniques. The overall aim is to understand how metabolism recycles the alkaloid skeleton, both in terms of the metabolic route(s) exploited and the reaction mechanisms of the enzymes involved. The former has been approached using high-resolution 2-dimensional NMR and GC-MS methods; the latter by determining kinetic isotope effects and modelling the potential reaction steps. It appears that the mechanism for nicotine demethylation in plants is similar to but has significant differences from that described for mammals and Pseudomonas bacteria. These differences are discussed.