Coagulation protein function VII: diametric effects of acetaldehyde on factor VII and factor IX function.
The first metabolite of ethanol, acetaldehyde, has the ability to form adducts with proteins and alter their function. It has been shown that acetaldehyde reacts with various proteins of the blood coagulation pathway and, subsequently, produces a prolongation of the clotting time. This study evaluated the function of clotting proteins from the extrinsic coagulation pathway (factor VII) and the intrinsic coagulation pathway (factor IX) when preincubated with acetaldehyde as compared to a control and compared to preincubation with ethanol. Prior to use in a clotting assay, incubation times with acetaldehyde, ethanol, and the control were the same for both factors VII and IX. An automatic fibrometer measured the clotting times. Factor VII preincubated with acetaldehyde prolonged the clotting time. However, factor IX preincubated with acetaldehyde actually decreased the clotting time. Of interest, both factors VII and IX preincubated with acetaldehyde produced statistically significant results when compared to the control and ethanol. This experiment indicates that acetaldehyde, in forming an adduct with proteins of the blood coagulation pathway, may induce a conformational change of factors VII and IX so as to either increase or decrease the clotting time. Therefore, it is possible that some of the deranged coagulation in alcohol abusers may be a final net result of the interaction of acetaldehyde and proteins of the coagulation pathway.
Sabol
D A
DA
Department of Medicine, Medical College of Ohio, Toledo 43614, USA.
Basista
M H
MH
Brecher
A S
AS
Haider
K
K
Kleshinski
J
J
D000079:Acetaldehyde / Q000494:pharmacology*; D001780:Blood Coagulation Tests; D000431:Ethanol / Q000494:pharmacology; D005164:Factor IX / Q000502:physiology*; D005167:Factor VII / Q000502:physiology*; D066298:In Vitro Techniques
D000431:Ethanol; D005167:Factor VII; D005164:Factor IX; D000079:Acetaldehyde