Caffeine: protector of plants

Ah, the smell of coffee brewing, of tea steaming, hot chocolate beckoning on a cold winter’s day… the fizzy kick of Coca-Cola on a long journey. It’s wonderful, really. The taste, feel and cultural significance of each of these drinks may differ, but they all share one key ingredient: caffeine. Caffeine is the most commonly used mood-altering drug for humans: it wakes us up, prepares our minds for work, keeps us alert (we think) and provides a shared experience during informal interactions.

But why do so many plants – coffee, tea, cocoa – make this wonderful chemical? It is seemingly tailor-made for human activity, but it clearly didn’t evolve simply to make us talk faster. It’s more likely to be a deterrent, keeping animals (including us) from eating the plant.

Chemical weaponry

Plants, being sessile, have to keep coming up with inventive ways to avoid being eaten. Some grow weirdly tall, with their fruits well out of reach of most opportunistic plant-eaters. Others grow fearsome armour, like thorns. But nearly all plants are loaded with a potent cocktail of nasty-to-animal chemicals, which have sickening or lethal properties for would-be consumers.

Making chemicals that influence the transmission of neuronal signals is a very successful approach, as even a tiny dose of such a chemical will have a huge effect on a plant-eating animal. Of course, to be successful, plant-eating animals must create workarounds. They have ‘clean-up’ systems that match the sophistication of poison production in plants.

When dangerous chemicals are absorbed in the gut, the bloodstream routes them through the liver to be filtered out. Wherever possible, they are captured and changed into innocuous forms that can usually be excreted (some are captured and imprisoned for life in the animal’s liver). Meanwhile, useful chemicals (sugars, amino acids, fats) are reformulated and packaged for onward use.

Caffeine and the chemical arms race

This chemical arms race has been going on ever since there have been animals that eat plants.

Plants have some of the most sophisticated ‘secondary’ metabolism on the planet. They can add, subtract, combine and modify carbon compounds better than the best minds in any chemical corporation.

Animals have an advanced arsenal of chemical-modifying enzymes, many of which are part of the cytochrome P450 family. The P450s have haem, which absorbs light at a specific wavelength (450nm) and so has a distinctive colour (the ‘P’ stands for ‘pigment’).

Most P450s can hold and position a ‘foreign’ organic compound and insert an oxygen into it. Once that happens the compound is changed, often into a substrate for other P450s or another part of the liver’s detoxifying system. Eventually (hopefully), the compound becomes inert and is excreted in urine.

Caffeine is one such poison-from-a-plant compound: it is a member of a class of compounds called alkaloids, which are a rich source of noxious chemicals for plants. Caffeine has many modes of operation, but its most well-known is binding adenosine receptors in the brain. These receptors signal drowsiness, so when caffeine blocks them, one gets a jolt of perception.

Robust machinery

But the same dose of caffeine that gives humans a little buzz is very dangerous – if not lethal – to many other mammals and insects. This is not because the mechanism is different; rather, it’s because in humans the specific cytochrome P450 that metabolises caffeine is so much more effective. A small dose of caffeine that’s gives us a pleasant ‘awake’ feeling is far too much for other animals, which overdose quickly on caffeine.

The constant evolutionary warfare between plants and animals is both a huge boon and a headache for humans. Many of the foods we treasure due to their taste or smell is thanks to this ‘secondary’ metabolism in plants, and numerous medical compounds have been discovered first in plants.

But the constant removal of foreign compounds by our liver means that all medicinal drugs have to be designed very precisely – just enough to do something, but not too much. Always running in the background is a complex biological machinery that has evolved specifically to seek out, neutralise and degrade these molecules.

Caffeine in EMBL-EBI data resources

Caffeine makes an appearance in many public data resources. You might also have a look at a short post on Cafestol, molecule of the month in September 2017.