http://www.signonsandiego.com/news/science/20021029-9999_1m29smoke.html
Scripps scientists link chemical in tobacco with onset of diseases
By Bruce Lieberman UNION-TRIBUNE STAFF WRITER October 29, 2002 A
naturally present chemical in tobacco may contribute to the onset of
diabetes, cancer, aging and Alzheimer's, two scientists at The Scripps
Research Institute in La Jolla have found. The chemical, called
nornicotine, "cooks" the body's proteins, triggering the same reaction
that turns burned sugar brown and causes food to spoil. "Nornicotine
permanently and irreversibly modifies proteins, which can affect their
overall function," said Scripps biological chemist Kim D. Janda. Janda
and Scripps researcher Tobin J. Dickerson have published their study in
the Proceedings of the National Academy of Sciences. The paper appeared
online yesterday and will be in print later this year. Nornicotine also
was found to react with prescription steroids, such as cortisone and
prednisone, potentially making them more toxic, Janda and Dickerson
found. In their study, titled "A previously undescribed chemical link
between smoking and metabolic disease," the scientists found that
nornicotine attaches itself permanently to steroids and certain amino
acids on the surface of proteins. Amino acids are the chemical building
blocks of proteins. Proteins, encoded by DNA, form the key structural
elements in cells and are responsible for all the cell's activities.
Once nornicotine modifies these steroids and proteins, the new molecules
interact with other chemicals in the body and create new compounds. Among
them are a variety of compounds known as advanced glycation endproducts,
which have been implicated in numerous diseases including diabetes,
cancer, atherosclerosis and Alzheimer's. "These advanced glycation
endproducts are not supposed to be (present in your body) naturally,"
said Dickerson. "Your body is not prepared for them." Janda and
Dickerson, testing the blood of 20 smokers and nonsmokers, found that the
smokers had higher levels of proteins that had been modified by
nornicotine than nonsmokers. The smokers also had higher levels of the
advanced glycation endproducts. Nornicotine, unlike nicotine, persists
in the bloodstream, suggesting that the chemical may contribute to
tobacco addiction, Janda and Dickerson said. The chemical nornicotine is
present in all tobacco products, including cigarettes and chewing
tobacco, and in nicotine gum and patches. "It's been thought of as a
little bystander," Janda said, adding that he plans to study nornicotine
in nicotine gum and patches. Their study was supported by the Skaggs
Institute for Chemical Biology at The Scripps Research Institute.
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