The first specific is designed to discover and identify the enzymes responsible for the oxidation of ethanol to acetaldehyde in the brains of mice.
The second aim i s to study the mechanisms by which the accumulation of acetaldehyde in the brain alters the effect of ethanol in the central nervous system. Preliminary results provide a correlation between ethanol induced hypnosis (sleep time) and brain acetaldehyde levels. It is a collaborative project between Dr. Sergey Zimatkin and his colleagues at the Institute of Biochemistry, Grodno, Belarus in the former Soviet Union and Dr. Richard Deitrich and his colleagues at the Alcohol Research Center at the University of Colorado Health Sciences Center. The Institute of Biochemistry in Grodno has long been known for its studies on the metabolism and actions of ethanol and have the expertise to carry out the biochemical studies necessary for this project. The animal breeding and behavioral tests will be conducted at the University of Colorado Alcohol Research Center. This Center has selectively bred mice for differential responses to ethanol and has a great deal of experience in the behavioral and genetic characterization of such animals. In addition, we now have acatalasemic mice as well as Cytochrome P450 2EI knockout mice. Since both catalase and this cytochrome have been implicated in ethanol oxidation, these knockout mice will be especially useful.
| Zimatkin, Sergey M; Oganesian, Nikolay A; Kiselevski, Yury V et al. (2011) Acetate-dependent mechanisms of inborn tolerance to ethanol. Alcohol Alcohol 46:233-8 |
| Vasiliou, Vasilis; Ziegler, Thomas L; Bludeau, Pequita et al. (2006) CYP2E1 and catalase influence ethanol sensitivity in the central nervous system. Pharmacogenet Genomics 16:51-8 |
| Zimatkin, Sergey M; Pronko, Sergey P; Vasiliou, Vasilis et al. (2006) Enzymatic mechanisms of ethanol oxidation in the brain. Alcohol Clin Exp Res 30:1500-5 |
| Deitrich, Richard; Zimatkin, Sergey; Pronko, Sergey (2006) Oxidation of ethanol in the brain and its consequences. Alcohol Res Health 29:266-73 |
| Quertemont, Etienne; Eriksson, C J Peter; Zimatkin, Sergey M et al. (2005) Is ethanol a pro-drug? Acetaldehyde contribution to brain ethanol effects. Alcohol Clin Exp Res 29:1514-21 |
| Deitrich, Richard A (2004) Acetaldehyde: deja vu du jour. J Stud Alcohol 65:557-72 |
