How Caffeine Works
This is how it keeps you awake
Ah, caffeine. It’s the one drug you can freely admit being addicted to without any social repercussions. Just imagine if it was anything else. “Ugh, I’m all grumpy in the morning until I’ve had my shot of heroin.” “I can’t get through a workday without my whiskey.” “No worries, boss. I’ll do it after my meth break.” “Hey mom! Come on in! I was just about to prepare myself a fresh line of coke. Do you want some?”
But have you ever wondered how caffeine actually works? What exactly does it do to you to give you that jolt of energy?
Well, it turns out it works the same way no matter how you consume it, whether it’s in the form of a hot beverage, a sugar-laden soda, or (I guess) an enema. Specifically, caffeine keeps you awake by acting as an adenosine-receptor antagonist. Huh? Don’t worry. By the end of this article you’ll perfectly understand what that bit of sciencebabble means.
What’s adenosine?
To understand caffeine, you first need to understand what adenosine is. And to understand adenosine, you need to understand ATP. In fact, you should know about ATP anyway. It’s such an important molecule that biochemists commonly refer to it as “the fuel of life.” So, let’s start with ATP.
As you might be aware, you need to eat food to stay alive. That’s not only because food provides the building blocks — the bricks — to build and repair your body, but also because food contains energy — energy your body needs to power your muscles, your brain, and all the other biological processes happening within you. However, you cannot just stick a piece of pizza into your brain and expect your brain cells to access that energy.
After all, no matter how small you make that slice, it will still be way too large to enter a microscopic cell. So, your food needs to be broken down — digested — into sufficiently small molecules that your body can use. That’s what your stomach and digestive tract do and one of the resulting broken-down molecules is glucose.
Unlike a slice of pizza, glucose is small enough to enter your bloodstream and can thus easily be distributed throughout your body. However, although glucose is small and contains energy, it’s still a little too clunky and unwieldy to be readily used for energy by your cells. So, glucose needs to be broken down even further. Luckily, the cells in your body have just the right machinery to do that, namely, the so-called mitochondria.
Mitochondria take a piece of glucose and some oxygen and break the glucose further down in a process called cellular respiration. One of the results of this further breakdown of glucose is ATP, which stands for adenosine triphosphate. That’s the aforementioned “fuel of life” and it’s got that grandiose nickname because ATP is what powers cells. Think of ATP as coins and of a cell as an arcade videogame machine. The cell only works when you load it with enough ATP.
No coins — no ATP — and the machine — the cell — stays off. Game over.
Now, ATP doesn’t quite look like a quarter dollar — it’s neither round, nor metallic, nor does it sport the profile of George Washington. Instead, it’s got a fancy chemical formula:
But don’t worry. I don’t want to bore you with chemistry — I’m a bit afraid of chemical formulas myself. So let’s simplify that whole thing and make it look a little less scary:
Phew… Okay. As you can see, ATP is made up of one adenosine molecule (that’s the thing caffeine is an antagonist of) and three phosphates. That’s why it’s called adenosine tri(three)phosphate (duh!).
Now, the energy that powers your cells is stored in the chemical bonds that tie together the phosphates:
And that chemical bond energy is released by a process called hydrolysis. If you’re familiar with such highfalutin words as hydroelectric or hydroponic, you may know that “hydro” means water. The ending “-lysis,” in turn, means breakdown. So, what’s hydrolysis? Well, it’s basically the breaking down of a chemical bond using water:
This breakdown releases a whole lot of energy and it’s this energy that your cells use. It powers the expansion and contraction of muscle cells, generates the electricity within the cells of your brain, fuels the building of complex molecules such as proteins and fats, enables the moving of stuff in and out of cells, and basically powers anything else necessary to keep you alive.
With one phosphate blasted away by hydrolysis, we’re now left with what’s called adenosine diphosphate (ADP), that is, one adenosine molecule attached to just two phosphates:
Those two phosphates still contain plenty of energy and so ADP can be further broken down in much the same way as ATP before:
With yet another phosphate blown away, we have one phosphate left and the resulting pair of one phosphate and one adenosine is called adenosine monophosphate (AMP):
And when that last phosphate is used up as well, we’re left with just a lonely molecule of adenosine:
So what’s adenosine? Well, besides being a caffeine antagonist, as we’ll see in a bit, it’s what’s left over after a teeny tiny ATP battery has been completely exhausted — after all the energy in its phosphates has been released by hydrolysis.
Adenosine makes you sleepy
You might have heard of melatonin, a sleep-inducing hormone your body oozes into your bloodstream as soon as it gets dark. However, melatonin and darkness are not the only things that make you sleepy. How tired you are also depends on how active you’ve been. Spend the day on the sofa, passively watching TV, and you won’t be too tired in the evening. But spend all day cramming for an exam, running around in circles in your living room, or straining on the toilet with constipation, and you’ll be dead tired in the evening from all that exertion.
This raises a question: what exactly is it about activity that makes you tired? Well, the more active you’ve been, the higher your energy needs have been, and the more ATP you’ve consumed. Having understood how ATP is broken down via hydrolysis into ADP, AMP, and eventually adenosine, you know that a whole lot of activity must result in the accumulation of lots and lots of leftover adenosine molecules. And it is precisely this accumulation of adenosine molecules that makes you sleepy.
Here, this is how it works. The neurons in your brain have receptors perfectly tailored for adenosine.
You can imagine these adenosine receptors as little docking stations waiting to be plugged by adenosine.
And once an adenosine molecule has plugged into such a receptor, this initiates a whole cascade of biochemical reactions that make your neurons sluggish. In essence, an adenosine molecule starts singing a lullaby to your neurons and so you get sleepy.
And, of course, the more adenosine molecules you have singing “twinkle twinkle little star,” the sleepier you get.
This is why the more active you’ve been — and thus the more adenosine has accumulated from ATP burning — the more tired you end up.
Caffeine interferes with adenosine’s lullaby
Okay. Now that we understand how activity makes you tired through the accumulation of adenosine, we’re ready to understand what it means for caffeine to be an adenosine antagonist.
Let’s put the chemical formulas of adenosine and caffeine side-by-side:
Don’t worry, I won’t go into chemistry now either. Just note that the parts of the formulas highlighted in red are kind of similar. We can think of it as adenosine and caffeine having more or less the same “shape:”
Adenosine and caffeine looking so similar, means that caffeine can also dock into the adenosine receptors in your brain:
However, unlike adenosine, a plugged in molecule of caffeine does not slow down the operation of your neurons. Although caffeine blocks an adenosine receptor, it just never things a lullaby and thus doesn’t make you sleepy. It simply occupies the space, keeping you awake by preventing adenosine from doing its job of singing “twinkle twinkle little star.”
Using science speak, we say that caffeine acts as an adenosine antagonist. An antagonist is, by definition, simply a substance that blocks some biochemical receptor. So, when we say that caffeine is an adenosine antagonist, what we’re saying is that caffeine is a substance that blocks adenosine’s function by clogging up its receptors. And since that function of adenosine is to make you sleepy, caffeine’s clogging up of adenosine receptors keeps you awake.
Adenosine’s revenge
Caffeine’s ability to block adenosine receptors is great. It allows you to power through slumps in your day without needing a screaming drill sergeant in your face. However, as with all drugs, it comes with a downside. Adenosine doesn’t like to just loiter around its receptors, being unable to sing its lullaby. So, your body, to compensate and appease the idle adenosine molecules, eventually grows new receptors.
This means that with new receptors, now some may end up being occupied by caffeine and others by adenosine:
As a result, your usual dose of caffeine no longer makes you hyper awake. Instead, you’re just in some intermediate state — neither too sleepy nor too alert. This is called caffeine tolerance and it’s why, once you’re used to caffeine, you need a much bigger dose to block those pesky new receptors too and feel that jittery buzz again. What’s worse, since you now have additional adenosine receptors, you’re now in for a bad time when you skip your usual caffeine boost. After all, with new receptors, it’s now possible for extra adenosine molecules to throttle down your brain.
The result? In the absence of caffeine, there’s now a whole cacophony of “twinkle twinkle little star” going on and you end up dreadfully tired without your usual shot of espresso.
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