Mitochondrial aldehyde dehydrogenase is isolated as a tetrameric enzyme but can in the presence of divalent ion cations be transformed into a more active dimeric enzyme. Cytosolic enzymes are not activated. The basic for the differences in response to physiological concentrations of Mg2+ and Ca++ ions will be investigated with horse liver enzymes. Experiments to determine the in vivo state of the enzyme will performed with rat and beef liver mitochondrial enzymes. These studies will include the use of in vivo inhibitors and in vitro hybridization of the isolated enzyme. The interrelationships between the concentration of mitochondrial aldehyde dehydrogenase and rates of aldehyde metabolism will be determined in liver slices which contain partially inactivated aldehyde dehydrogenase. An investigation of the mode of inhibition of the enzyme by various propargyl derivatives will be undertaken in order to develop potential suicide or affinity inhibitors. Lastly, the effect of alcohol on the liver isozyme pattern and molecular aggregation of aldehyde dehydrogenase will be determined in rats made dependent upon alcohol.

Agency
National Institute of Health (NIH)
Institute
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Type
Research Scientist Award (K05)
Project #
5K05AA000028-08
Application #
3075245
Study Section
Alcohol Biomedical Research Review Committee (ALCB)
Project Start
1983-12-01
Project End
1988-11-30
Budget Start
1985-12-01
Budget End
1986-11-30
Support Year
8
Fiscal Year
1986
Total Cost
Indirect Cost
Name
Purdue University
Department
Type
Earth Sciences/Resources
DUNS #
072051394
City
West Lafayette
State
IN
Country
United States
Zip Code
47907
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Sanny, C G; Weiner, H (1987) Inactivation of horse liver mitochondrial aldehyde dehydrogenase by disulfiram. Evidence that disulfiram is not an active-site-directed reagent. Biochem J 242:499-503
McMichael, M; Hellstrom-Lindahl, E; Weiner, H (1986) Identification and selective precipitation of human aldehyde dehydrogenase isozymes using antibodies raised to horse liver aldehyde dehydrogenase isozymes. Alcohol Clin Exp Res 10:323-9
Tank, A W; Deitrich, R A; Weiner, H (1986) Effects of induction of rat liver cytosolic aldehyde dehydrogenase on the oxidation of biogenic aldehydes. Biochem Pharmacol 35:4563-9
Svanas, G W; Weiner, H (1985) Aldehyde dehydrogenase activity as the rate-limiting factor for acetaldehyde metabolism in rat liver. Arch Biochem Biophys 236:36-46
Svanas, G W; Weiner, H (1985) Use of cyanamide to determine localization of acetaldehyde metabolism in rat liver. Alcohol 2:111-5
Hellstrom-Lindahl, E; Weiner, H (1985) Effects of disulfiram on the oxidation of benzaldehyde and acetaldehyde in rat liver. Biochem Pharmacol 34:1529-35
Svanas, G W; Weiner, H (1985) Enzymatic requirement for cyanamide inactivation of rat liver aldehyde dehydrogenase. Biochem Pharmacol 34:1197-204