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 concomitant circulating acetaldehyde levels.
Brecher
A S
AS
Department of Chemistry, Bowling Green State University, OH 43403.
Thevananther
S
S
Franco-Saenz
R
R
D000079:Acetaldehyde / Q000008:administration & dosage / Q000494:pharmacology*; D000595:Amino Acid Sequence; D000818:Animals; D004305:Dose-Response Relationship, Drug; D004646:Emphysema / Q000209:etiology; D000431:Ethanol / Q000378:metabolism / Q000494:pharmacology; D006801:Humans; D008969:Molecular Sequence Data; D010196:Pancreatic Elastase / Q000037:antagonists & inhibitors*; D013552:Swine; D000515:alpha 1-Antitrypsin / Q000494:pharmacology*
D000515:alpha 1-Antitrypsin; D000431:Ethanol; D010196:Pancreatic Elastase; D000079:Acetaldehyde