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Nicotine link to ageing and cancer – new research 29/10/02 – US researchers have discovered that a chemical called nornicotine – which is naturally present in tobacco and is also produced as a metabolite of nicotine – may contribute to the pathology of diabetes, cancer, ageing, and Alzheimer’s disease.

In an article to be published in the Proceedings of the National Academy of Sciences, the researchers from The Scripps Research Institute (TSRI) have uncovered a previously unrecognised chemical process through which nornicotine reacts with the body’s proteins. “Nornicotine permanently and irreversibly modifies proteins, which can affect their overall function,” said Dr Kim Janda.

This process is the chemical equivalent of cooking and is the same reaction that causes food to age and spoil. Furthermore, the ‘cooking’ of proteins is just the tip of the iceberg. Nornicotine also reacts with commonly prescribed steroids, like cortisone and prednisone, potentially making them more toxic or compromising the effectiveness and safety of these drugs, reported the researchers.

In the so-called ‘cooking’ process, the chemical nornicotine attaches itself ‘covalently’ (permanently) to steroids and to certain amino acids on the surface of proteins, the scientists explained. These modified steroids and proteins can then interact with other chemicals in the body. Significantly, nornicotine-modified proteins can react to form a variety of compounds known as advanced glycation end products. “These advanced glycation endproducts are not supposed to be [present in your body] naturally,” said Tobin Dickerson, a Ph.D. student in TSRI’s Kellogg School of Science and Technology. “Your body is not prepared for them.” Advanced glycation end products have previously been implicated in numerous diseases including diabetes, cancer, atherosclerosis, and Alzheimer’s disease. The study shows a direct link between tobacco use and the development of these advanced glycation end products.

When they tested the blood of smokers and non-smokers, the researchers found that the smokers had higher levels of the nornicotine-modified proteins than non-smokers. The smokers also had higher levels of the advanced glycation end products.

The persistence of nornicotine in the bloodstream, as opposed to nicotine, which quickly disappears after cessation of smoking may also suggest a role for nornicotine in contributing to the biological mechanisms of tobacco addiction, since the nornicotine provides a long-lived source of nicotine-like molecules.

The work highlights the need for more studies into the consequences of exposing the human body to nicotine metabolites, like nornicotine. Source: roceedings of the National Academy of Sciences, 28 October, online edition

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