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Nicotine Tied to Harmful Protein Changes

Study suggests it's not just the tar in tobacco that's damaging

MONDAY, Oct. 28, 2002 (HealthDayNews) -- Nicotine may hook you but it's the tar in tobacco that does you harm, right?

Don't be so sure. The chemical that gives tobacco its pull sears proteins much the way foods brown, leading to potentially harmful changes that could cause disease, a new study has found.

The leader of the research, Kim Janda of the Scripps Research Institute in California, cautions it's too soon to know if the protein damage indeed causes health problems for nicotine users. However, recent evidence suggests that this so-called protein, glycation, in which sugars fuse with proteins to generate advanced glycation end-products (AGEs), is linked to vessel disease, diabetes and other ailments. Janda's study found smokers have more of these AGEs in their blood than do nonsmokers.

And it's not only smokers who are vulnerable, Janda adds. "You can get this from the [nicotine] patch or gum." A report on the findings appears in today's issue of the Proceedings of the National Academy of Sciences.

Janda and Tobin Dickerson, another Scripps scientist, first showed that nornicotine, which is produced in the breakdown of nicotine, can hook up with glucose and bind to proteins in a dish. Then they sampled the blood of 10 smokers and nonsmokers to look for the abnormal molecules.

Using a small immune agent called an antibody that specifically hunts for glycated proteins, the researchers saw that smokers had many more abnormal molecules.

Janda says he's not sure what to make of that finding: "The implication is that [nicotine] can react with proteins and can alter their function. Whether that's bad, that's a possibility. In some cases maybe it could be good, but clearly you're changing protein's overall structure and that's something that was not intended to be."

Since the function of a protein depends on its shape, altering the structure can render it useless or harmful. Similarly, if the protein is an enzyme that stimulates chemical reactions, changing its shape can stunt its job performance.

Nicotine may also hinder the effects of some drugs. The researchers found that nornicotine modified the structure of prednisone, a commonly prescribed steroid with similarities to glucose. Janda said there may be other drugs besides steroids that are vulnerable to the alterations.

Population studies have hinted that nicotine -- or at least, smoking -- may shield the brain from neurological diseases such as Parkinson's and Alzheimer's, says George Koob, a Scripps tobacco expert. However, it's not certain how much of this is explained by smokers dying younger than nonsmokers.

Koob, who was familiar with the latest findings, calls the work "very interesting," but adds that more studies are needed to say if the effects of AGEs from nicotine are "good, bad or indifferent."

What To Do

For more on the adverse effects of smoking, try the U.S. Centers for Disease Control and Prevention or

SOURCES: Kim Janda, Ph.D., professor, chemistry, Scripps Research Institute, La Jolla, Calif.; George Koob, Ph.D., professor, neuropharmacology, Scripps Research Institute, La Jolla, Calif.; Oct. 28, 2002, Proceedings of the National Academy of Sciences
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