Why would anyone pay to get fruit flies drunk? In the October 2009 issue of Genetics, North Carolina State University and Boston University joined together for a genome-wide association study to identify an enzyme that is associated with consuming alcohol. In this experiment, the effects of alcohol on fruit flies were evaluated and the results were translated to humans for applicability of study.
They identified seven intronic single nucleotide polymorphisms (SNPs) of the Malic Enzyme (MEN) 1 gene in fruit flies that altered under the influence of alcohol. A SNP represents a single building block to DNA for example cytosine (C) or adenine (A). Therefore, they discovered seven specific locations in the MEN that have an altered nucleotide from the norm. Since the SNPs are different, scientists can locate these specific nucleotide “markers” and see how they affect the gene’s function.
The graph to the left plots the MEN activity versus the standardized MET, the mean elution time, for all the fruit flies after the second exposure to alcohol. The MET, in other words, is the amount of time the fly resembled a drunken person until it passed out and could no longer fly. Therefore, the larger that value the MET is, the higher the tolerance the fruit fly has to alcohol. The fruit flies that displayed a higher tolerance also displayed a higher MEN activity. 
The MEN is a critical metabolic link of the glycolytic pathway to the tricarboxylic acid cycle by converting malate into pyruvate. If this enzyme activity increases with the increase in alcohol tolerance, the MEN would be creating an excess of pyruvate. Who cares what pyruvate is, it doesn’t affect me; Right? No, even without understanding what pyruvate is, an excess of anything in the body is not healthy. The body will convert excess material into fat to store “energy”. In this case, pyruvate can lead to fatty liver syndrome.
The isolation of this enzyme in humans altered in the same trend when intoxicated as seen in the fruit flies. Researchers have been able to find these “markers” in generations of families or civilizations and have linked the SNPs to diseases. In other words, you have a higher susceptibility to alcoholism, if family members are alcoholics.
The research done by these two universities has proven to be significant. Tolerance and sensitivity to alcohol can be defined and explained by the changes in theses seven nucleotides. The result confirms alcoholism as a disease and explains how it can be passed through generations of families. From this research, a drug company will be able to synthesize a drug that will reduce the MEN activity that is enhanced when intoxicated. This is the first leading step in analyzing alcoholism for humans. Will this new drug be able to “cure” alcoholism? We will have to wait and find out.
Reference:  Morozova, Tatiana V., Julien F. Ayroles, and Katherine W. Jordan. “Alcohol Sensitivity in Drosophila: Translational Potential of Systems Genetics.” Genetics. 183 (2009): 733-745.
Photo: M. Plonsky 2004