Ethanol: why?

Over the Christmas holiday, quite a few of us will consume ethanol-containing products. This simple, two-carbon molecule is a potent (and legal) mood-altering drug that is woven into the fabric of European and many other cultures since time immemorial. Ethanol has been part of the furniture of human civilization since enterprising farmers discovered it in rotten fruit. It is only fitting that it features prominently at Christmas, a winter feast of excess.

Ethanol was not originally made to take the edge off of awkwardness at parties. It is for the most part made by yeast: a single cell fungus that moves from fruit to fruit. Yeast has its own agenda. It produces ethanol by fermenting sugar – that is, it manages to oxidise them without needing to bring in fresh molecular oxygen.

Many organisms can do this – extract energy from food without using oxygen (‘anaerobic metabolism’). After all, there is a place for everyone at life’s table, and not all life forms have the luxury of an oxygen-rich environment, where ‘aerobic’ metabolism can release scads of energy per carbon molecule.

Bacteria that live in oxygen-free environments, like deep earth or the stomachs of ruminants, still use the machinery of carbon metabolism without molecular oxygen. Our muscles switch to anaerobic metabolism to give a quick burst of energy, over and above the flux of oxygen being carried by the blood. Our anaerobic metabolism produces lactic acid, which then has to be processed (at cost) back into normal sugars.

Yes but why?

So far, so teenage biology class. But here’s where it gets weird. When it finds itself with an excess of sugar on its hands, yeast switches over to fermentation (anaerobic) metabolism, even though oxygen is present and available. Why would it do this?

Scientists are still understanding this process (and it took some sleuthing on my part to find out the current research), but then, if you think about all the competition that must be happening on rotting fruit, it all becomes clearer.

Yeast gets the edge over the competition by fermenting sugar into ethanol, in three ways:

  1. When sugar is plentiful, yeast can make as much – if not more – energy per unit of time by going the fermentation route. If you are competing for a lot of input, you are more worried about the rate than the efficiency of your metabolism.
  2. When yeast have exhausted their sugar supplies (by fermenting them to ethanol), they can consume the ethanol aerobically, hopefully at their leisure. Not every competing bacterium or fungus can do this, so by converting sugar to ethanol as quickly as possible the yeast exploits the cornucopia immediately. It can grow, and store the energy in a hard for the competition to use way for later consumption.
  3. Yeast has adapted to high levels of ethanol, which is pretty poisonous to most other organisms. Its ethanol fermentation can be described as a ‘sugar land grab’ coupled with competition suppression.

Up the fruit chain

Yeast’s winning formula for exploiting sugar-filled fruit has knock-on effects right up the food chain. Every animal that eats fruit regularly has to be able to handle ethanol. Fruit-flies, badgers, Arsenal fans – all of them need the right mixture of enzymes to process large levels of ethanol.

Fruit-eating animals possess a battery of detoxifying enzymes, mainly housed in the liver, that can process ethanol and other short chain alcohols. These enzymes are all variations on alcohol dehydrogenase (ADH), with many subtle differences that enable them to handle more than just ethanol detoxification.

To detox, or not to detox?

But there is more than one way to detox. The human agricultural revolution seems to have triggered a second wave of selection for an alternate detoxification pathway. This is most obvious in far-east Asian populations, where an ADH pathway that is pretty lousy at handling ethanol has clearly been under selection. Perhaps this is because by making alcohol more obviously toxic to an individual, one can stem the onset of rampant alcoholism.

Rampant alcoholism was pretty much a requirement in Early Mediaeval Europe, on the other hand. People there relied on hop-infused, lightly fermented sugary water (beer) as one of the main ways to achieve water purification. Even young children would be served ‘small beer’ (under 1% alcohol) every day. (Hops flowers contain powerful anti-microbials; it seems likely the addition of sugar, in the form of Barley, and fermentation to ethanol was simply to make the beer palatable).

Unsurprisingly, the toxicity-enhancing variation on alcohol metabolism that flourished in far-eastern Asia is quite rare in Europe.

Raise a glass

We still do not understand all the forces of selection on alcohol processing in humans and other animals. But it is clearly one area of our genome that has changed recently.

When you raise your glass of wine (or beer) tonight (or tomorrow), or douse a pudding (or dessert) in brandy, take a moment to appreciate the gift of yeast, and how this humble creature has moved us, both evolutionary and culturally.

Ethanol in EMBL-EBI data resources

As in life, ethanol is just about everywhere in the public archives.

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