Biosynthesis of Piperidine-Piperideine-Type Nicotinoids

The biosynthesis of the piperidine-type nicotinoid anabasine proceeds in an analogous manner to nicotine, with A -piperideine (instead of the A-methyl-A -pyrrolinium cation) as the counterpart of nicotinic acid/3,6-dihydronicotinic acid (Leete 1969). Consequently, L-lysine is the source of the piperidine ring instead of L-omithine (Solt et al. 1960). Unlike the conversion of the latter to the N-methyl-A -pyrrolinium cation via free putrescine, the conversion of lysine to A -piperideine is assumed to proceed via a bound cadaverine (Friesen et al. 1992). 

According to a proposal of Leistner and Spenser (1973) the sequence proceeds via the Schiff base between lysine and pyridoxal-5-phosphate (phosphate of vitamin Bg) and similarly bound cadaverine. Anabasine isolated from 2 - C, C-labeled anatabine-fed plants turned out to be unlabeled indicating that anabasine was not formed by the reduction of anatabine (Leete 1979). 

Numerous effects of nicotine, sometimes also including those of its congeners, on mammalian enzymes have been reported, e.g. competitive inhibition of certain enzymes of the glucocorticoid and sex steroid biosynthetic pathways, e.g., the 

3 a-hydroxySteroid dehydrogenase in canine prostate (Meikle et al. 1988), the human fetal adrenal mitochondrial lip-hydroxylase as well as the microsomal 21-hydroxylase (Barbieri et al. 1989). The nicotine metabohte cotinine showed similar results with the exception of the inhibition of the 21-hydroxylase. Anabasine turned out to be the most potent inhibitor of these three nicotinoids in rat adrenal 

2 in PC 12 cells (Shaw et al. 2003). Such results seem to be of significance with respect to the health-damaging aspects of tobacco smoke. 

---