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A nicotine by-product reacts with proteins, say scientists at TSRI

October 24, 2002, La Jolla, CATwo researchers at The Scripps Research Institute (TSRI) 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, aging, and Alzheimers disease.

In an article to be published in the Proceedings of the National Academy of Sciences, the researchers have uncovered a previously unrecognized chemical process through which nornicotine reacts with the bodys proteins.

Nornicotine permanently and irreversibly modifies proteins, which can affect their overall function, says Kim Janda, Ph.D., who holds the Ely R. Callaway, Jr. Chair in Chemistry at TSRI.

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

How Nornicotine Cooks Proteins
The chemical nornicotine attaches itself covalently (permanently) to steroids and to certain amino acids on the surface of proteins. 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 endproducts.

These advanced glycation endproducts are not supposed to be [present in your body] naturally, says Tobin Dickerson, a Ph.D. student in TSRIs Kellogg School of Science and Technology. Your body is not prepared for them.

Advanced glycation endproducts have previously been implicated in numerous diseases including diabetes, cancer, atherosclerosis, and Alzheimers disease. Dickerson and Jandas study shows a direct link between tobacco use and
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Contact: Jason Bardi
jasonb@scripps.edu
858-784-9254
Scripps Research Institute
28-Oct-2002


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