Drosophila alcohol dehydrogenase: stereoselective hydrogen transfer from ethanol.

Drosophila alcohol dehydrogenase shows a broad substrate specificity, with secondary alcohols being better substrates than primary alcohols. This specificity indicates that the active site contains two hydrophobic interaction sites and hence, a primary alcohol should be able to bind in two productive modes. This was tested by studying the activity of the enzyme with ethanol, [2H6]-ethanol and 1S-[2H1]-ethanol. An identical primary kinetic isotope effect of 2.5 for the two deuterated ethanols showed that deuterium was transferred from the enantiomeric 1S-[2H1]-ethanol to the coenzyme. Thus, ethanol interacts with only one hydrophobic region of the active site.