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Aspects of the oxidative metabolism of nicotine

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Conclusions

The balance of the excreted sum of nicotine and its known metabolites from confirmed results reflects great progress in recent years and today accounts for about 40–60% of the estimated or known intake of the alkaloid, calculating on the basis of parts of well-defined and reliably determined species. The main part of this balance is accounted for by products of the α-oxidation of nicotine in the 5′-position. A further 40% has recently been attributed to those parts of metabolites which are additionally found after the treatment of urine samples with enzymes generally known to act on phase II metabolites. Conjugates of nicotine, cotinine, and trans-3′-hydroxycotinine are held responsible for this. Recently, some of these products have been definitely characterized and determined by direct measurements.

Quantitative data are missing on the Δ1′,2′-iminium ion, the very recently identified tautomer of 2-hydroxynicotine in urine, and the nature of its prevailing tautomeric form which both are biologically high importance, have there been reports so far on the mechanism for their metabolic formation. Further, the metabolic fate of nornicotine, the first metabolite of the intermediary methylene iminium species, is still awaiting elucidation. Nornicotine is excreted in only a very small ratio. This may be caused by demythylation or by oxidation. Further conclusions require knowledge of the actual structures of the nicotine metabolites under different analytical pH values or in organic solvents. The respective proportions of the tautomeric structures in the biological media in general and especially at the active sites of enzymes determine the metabolic pathways of nicotine and its subsequent metabolites and should be the aim of intense investigations.

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  1. Institut für Biopharmazeutische Mikroanalytik, Hexentwiete 32, D-22559, Hamburg, Germany

    G. B. Neurath

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Neurath, G.B. Aspects of the oxidative metabolism of nicotine. Clin Investig 72, 190–195 (1994). https://doi.org/10.1007/BF00189309

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