In humans and many other animals, they serve to break down alcohols that otherwise types of alcohol pdf toxic, and they also participate in generation of useful aldehyde, ketone, or alcohol groups during biosynthesis of various metabolites. Early on in evolution, an effective method for eliminating both endogenous and exogenous formaldehyde was important and this capacity has conserved the ancestral ADH-3 through time. Gene duplication of ADH-3, followed by series of mutations, the other ADHs evolved. Though this feature is not adaptive from an energy point of view, by making alcohol in such high concentrations so that they would be toxic to other organisms, yeast cells could effectively eliminate their competition.
This was thought to explain the conservation of ethanol active ADH in other species than yeast, though ADH-3 is now known to also have a major role in nitric oxide signaling. Histidine or an Arginine residue in the enzyme catalyzing the conversion of ethanol into acetaldehyde. In the Histidine variant, the enzyme is much more effective at the aforementioned conversion.
The enzyme responsible for the conversion of acetaldehyde to acetate, however, remains unaffected, which leads to differential rates of substrate catalysis and causes a buildup of toxic acetaldehyde, causing cell damage. In humans, various haplotypes arising from this mutation are more concentrated in regions near Eastern China, a region also known for its low alcohol tolerance and dependence. A study was conducted in order to find a correlation between allelic distribution and alcoholism, and the results suggest that the allelic distribution arose along with rice cultivation in the region between 12,000 and 6,000 years ago.