A 53-year-old man, who has been smoking for the past 35 years at a 2-pack-a-day rate, visits his physician for a cough that will not go away and for difficulty in breathing. A chest X-ray rules out cancer but does display an increased anterior-posterior (AP) diameter, flattened diaphragms, and “air trapping.” The patient is told that his condition will not improve and that he needs to stop smoking to stop the progression of the disease. At the molecular level, this disease is caused by which one of the following?
Correct Answer: Decreased a1-antitrypsin activity in the lung
Description: The man has the symptoms of emphysema, caused by destruction of lung cells by the protease elastase. Neutrophils in the lung accidentally release elastase as they engulf and destroy inhaled bacteria and other particles, and normally, a1-antitrypsin would bind to the elastase and inhibit its activity. In a long-term smoker, however, products from the cigarette smoke oxidize an essential methionine side chain in a1- antitrypsin, rendering it inactive. Thus, overtime, noninhibited elastase has been destroying lung tissue until the lung no longer functions properly. Even though the inhibitor will block trypsin activity, the lung damage is the result of increased elastase activity, not trypsin activity. Sulfhydryl groups are not being affected, rather a sulfur in methionine is the target of the cigarette smoke.
Category:
Biochemistry
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