Quitting smoking really is more difficult for some people than others -- and it's not just a matter of weak willpower, as many people believe. Levels of a particular liver enzyme that metabolizes nicotine are an indicator of how likely it is that a smoker will become addicted, scientists have learned. Quantities of the enzyme produced by the body vary widely among individuals and ethnic groups, but the less you have, the greater your chances of success.
About Enzymes
Enzymes are tireless facilitators of all metabolic processes. Without them, essential chemical reactions within the human body would occur too slowly to sustain life. As catalysts, enzymes mediate chemical reactions and accelerate the speed at which they occur, often by as much as a million times, without undergoing change themselves. Many inherited genetic conditions are the result of enzyme deficiencies, and the efficacy of many prescription drugs depends upon interactions with enzymes. The thousands of types of enzymes in the human body each have highly specialized metabolic functions.
The Smoker's Enzyme
When a smoker draws on a cigarette, nicotine enters the bloodstream via the lungs, circulates through the body, and ultimately reaches the liver, where toxic substances are neutralized. A liver enzyme known as CYP2A6 is responsible for degrading about 80 percent of ingested nicotine but "huge variation" exists among individuals in the quantities produced, says nicotine addiction expert Dr. Rachel Tyndale of the Centre for Addiction and Mental Health in Canada. Smokers with low levels of CYP2A6 tend to be satisfied with fewer cigarettes because the nicotine stays in their systems longer. When levels of the enzyme are high, the liver clears nicotine out faster, so people have to smoke more cigarettes in order to get the same pleasurable effect, making them more likely to become addicted.
Activation of Carcinogens
Although CYP2A6 breaks down nicotine, another function is hazardous to health: the same enzyme also activates some of the carcinogens in tobacco smoke, say scientists at the Scripps Research Institute. Drugs that inhibit the liver's production of CYP2A6 exist, but they have too many adverse side effects to be used as smoking cessation aids. However, in early 2011, addiction research scientists at the the Academy of Finland initiated a project to develop a CYP2A6 inhibitor designed specifically to help smokers cut down -- and therefore quit -- more easily.
Ethnic Differences
When a CYP2A6-inhibiting drug specifically for smoking cessation comes on the market, dosages may have to be adjusted for smokers of different ethnic groups. According to a study published in the January 2002 "Journal of the National Cancer Institute," Chinese-Americans draw in less nicotine per cigarette, metabolize nicotine at about two-thirds the rate of Latinos and non-Latino Caucasians and have a much lower rate of smoking-related lung cancer. An earlier study by the same researchers at the University of California, San Franscisco, found that although Caucasians and African-Americans smoked about the same amount, the latter inhaled more deeply, the presumed reason for the higher incidence of lung cancer in that group. These studies support "growing evidence that ethnicity can significantly alter response to drugs."
References
- Canadian Institute of Health Research: Research Profile; Can't Stop Smoking? Blame Your Liver.
- "Current Cardiovascular Risk Reports"; The Role of Genetics in Nicotine Dependence...; James MacKillip et al; Sept. 7, 2010
- National Digestive Diseases Clearinghouse: Smoking and Your Digestive System
- University of California at San Francisco; Center for Health and Community; Some Ethnic Differences in Lung Cancer Rates...; Jan. 15, 2002
- The Scripps Research Institute; Scripps Research Scientists Describe Smoker's Enzyme; Aug. 26, 2005
- Biology Reference: Enzymes
