ACETALDEHYDE INHIBITS THE ANTI-ELASTASE ACTIVITY OF ALPHA(1)-ANTITRYPSIN

There are genetic and exogenous factors responsible for alpha(1)-antitrypsin (alpha(1)-AT) deficiency which may lead to cirrhosis of the liver and emphysema. The present study was initiated on a biochemical level in order to determine whether acetaldehyde, the major product of ethanol metabolism, is capable of influencing the physiological effect of alpha(1)-AT upon elastase, an enzyme which is capable of inducing emphysema. The effects of acetaldehyde and ethanol upon elastase and alpha(1)-AT were tested. Acetaldehyde at 0.3-M and 1.2-M concentrations inhibited the anti-elastase activity of alpha(1)-AT Acetaldehyde at 0.03-M and 0.07-M concentrations did not affect elastase activity and had a slight effect at 0.12-M levels. Equivalent amounts of ethanol were without influence upon elastase activity or alpha(1)-AT function. These data provide biochemical support for the possibility that heterozygous males with lower than normal alpha(1)-AT levels may be at much higher risk to develop liver disease, emphysema, and alpha(1)-AT deficiency as a consequence of chronic exposure to ethanol and concommitent circulating acetaldehyde levels.