Molecular control of the induction of alcohol dehydrogenase by ethanol in Drosophila melanogaster larvae.

The activity of alcohol dehydrogenase (ADH:EC 1.1.1.1), the initial enzyme in the major pathway for ethanol degradation, is induced in Drosophila melanogaster larvae by low concentrations of dietary ethanol. Two lines of evidence indicate that the metabolic products of the ADH pathway for ethanol degradation are not directly involved in the induction of Adh. First, the accumulation of the proximal transcript in Adhn2 larvae was increased when the intracellular level of ethanol was elevated. In addition, the ADH activity, the proximal Adh mRNA, and the intracellular concentration of ethanol were elevated coordinately in wild-type larvae fed hexadeuterated-ethanol, which is metabolized more slowly than normal ethanol. An examination of P element transformant lines with specific deletions in the 5' regulatory DNA of the Adh gene showed that a DNA sequence between +527 and +604 of the distal transcript start site is essential for the induction of the Adh gene [corrected]. The DNA sequence between -660 and about -5000 of the distal transcript start site was important for the down-regulation of the induction response.