Smokers and nonsmokers often wonder what the body does with nicotine---the addictive compound in tobacco---once the chemical enters the bloodstream. The liver is the body's primary detoxification organ, and is responsible for converting harmful substances into less-toxic ones, or at least into substances that can be eliminated through one of the body's several chemical elimination routes. Nicotine is no exception: The liver processes and converts it into somewhat less-toxic compounds through a long series of chemical reactions.
Nicotine Iminium Ion
The first metabolite, or chemical product, of nicotine breakdown is the nicotine iminium ion, according to an article published in Pharmacological Reviews in 2005. A liver enzyme called cytochrome P450 accomplishes this transformation, in which an enzyme is a protein molecule that helps chemical reactions take place faster than they otherwise would. Enzymes are important to the metabolism of nicotine, and other toxins, by the liver because they speed up the rate at which toxins are removed from the system.
Cotinine
The nicotine iminium ion goes on to react with another liver enzyme, called aldehyde oxidase, producing the chemical compound, cotinine. This molecule occurs naturally in tobacco along with nicotine, and acts similarly to nicotine in the body, though it is less potent. While cotinine itself is not necessarily a desirable metabolite of nicotine---the liver goes on to produce other compounds from cotinine that are more easily excreted---it's a necessary chemical intermediate in the overall nicotine-metabolism process.
Cotinine Metabolites
Cotinine is broken down through several pathways, according to an article in The Pharmacogenetics Journal, which compiles information on enzymes and the genes that code for them. Among the products of cotinine breakdown are 3-hydroxycotinine and 3-hydroxycotinine glucuronide. These compounds are both water-soluble and are passed in the urine.
Nicotine N-Oxide
The conversion of nicotine to the nicotine iminium ion is not the only possible metabolic fate of nicotine in the liver. Some nicotine is instead converted to a chemical called nicotine N-oxide by the liver enzyme, FMO3. This reaction is not as favorable as that which forms the nicotine iminium ion, however, and according to Pharmacological Reviews, occurs less than 10 percent of the time. Nicotine N-oxide appears to undergo no further chemical metabolism, notes The Pharmacogenomics Journal, and can be converted back into nicotine by the liver. As such, this conversion reaction somewhat slows the rate of nicotine elimination by the body.
References
- "Pharmacological Reviews"; Metabolism and Disposition Kinetics of Nicotine; Janne Hukkanen, et al; March 2005
- "The Pharmacogenomics Journal"; Integrating Genotype and Phenotype Information; T. Klein et al.; May 2001
