New Ideas About Origin of Alcohol Metabolism

Although observing a college student’s weekend habits wouldn’t suggest it, ethanol is, in fact, a toxic substance. Left unmetabolized, it acts as a central nervous system depressant by working as a GABA agonist at the synapse.

            

Since GABA functions primarily as an inhibitory neurotransmitter, a flood of “GABA-imitating” alcohol into the synapse means neurons that normally receive an action potential from a presynaptic neuron actually silence that impulse before it can travel where it needs to go. The haywire this creates in the nervous system presents itself initially as euphoria and relaxation, but as blood alcohol content rises and more inhibition takes place, the consequences become more severe (nausea, impaired cognition, unconsciousness, etc).

            

Luckily, not all ingested ethanol ends up in the bloodstream. Humans are able to metabolize a certain amount of ethanol through the action of alcohol-dehydrogenase, which converts it into acetylaldehyde. Other enzymes produced by the liver then rapidly convert toxic acetylaldehyde to acetate and eventually carbon dioxide and water.

            

This safety mechanism is great for having a little fun on a Friday night without worrying about shutting down your nervous system (although some of us almost manage to do that). But how and why, evololutionarily speaking, did we evolve the ability and motivation to consume this poison?…especially when many animals, including primates, get by without consuming it or being able to metabolize it.

Steven Benner, of the Foundation for Applied Molecular Evolution in Gainesville, Fla., sought to answer this question by tracing the history of the alcohol-dehydrogenase (ADH4) back through the primate family tree. Benner looked at the changes in the enzyme at each branching point in the phylogeny and was able to evaluate the effectiveness of each variant in metabolizing alcohol.

He found that most extinct primate ancestors (“branching points” on the tree) were not able to digest ethanol. However, the common ancestor of humans, gorillas, and chimps possessed ADH4 that was 50 times stronger than previous enzymes. Interestingly, these primates spend more time on the ground than other species. Brenner hypothesizes that the “terrestrial lifestyle” of our common ancestor gave it more access to fruits that had fallen from the tree. Many of these fruits had breaks in the skin that could allow yeast to enter and ferment sugar into ethanol.

Obviously, primates that did not possess the enzyme could not eat these fruits without passing out and possibly falling victim to ground-restricted predators. Those that could metabolize the ethanol were free to enjoy as much of this uncontested resource as their livers could handle. Benner’s hypothesis also explains why extant primarily tree-inhabiting primates cannot metabolize ethanol—they were not exposed to the fallen fruit, only fruit still attached to the tree.

Although Benner’s explanation is certainly convincing, it will take a little support from the fossil record (there is little fossil evidence of human and primate ancestors during this time period) for his ideas to be more widely accepted. Until then, all we can do is lift our glasses to the nameless ancestor who, 10 million years ago, was bold enough to step down from his tree and make it possible for us to “enjoy responsibly”.

Posted by Joseph Starrett (3)