I never really thought about this,
even though my morning cold brew is basically load bearing at this point.
But how exactly does this coffee help me wake up in the morning?
I know it comes down
to this critical chemical caffeine, but at the molecular level,
what is this little nub doing to make me feel more alert?
Is this an energy source or is it something weirder?
The answers here can take us in some wild directions.
From the delicate balance of competing signals in your brain to the dark depths
of what potentially makes our metabolism kind of dangerous.
So I'm not going to waste any time Slam a shot of espresso, and let's take a quick
look into the pharmacology of how caffeine perks you up.
And hey, welcome back to
clockwork, a show about the chemistry powering your foundations.
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But anyway, in order to understand how caffeine works, its best to see it first.
So let's take a proper look at caffeine, the molecule real quick.
Caffeine is incredibly well studied, with at first being
properly identified all the way back in the 19th century.
So there's dozens of different ways to describe this goofy little wedge.
But for now, I'm going to focus on the fact that caffeine is a purine,
which is any molecule that kind of has this shape, which is a little hexagon
glued to a little pentagon, which is as far away
from a technical definition appearing as you can get.
But that's what I'm rolling with for now.
And maybe that purine label sounds familiar.
If not, let's compare caffeine to an equally famous purine.
This fella is adenosine, and trust me, you know this one.
Slap a ribose sugar and three phosphate on that purine base.
And heck, you've got adenosine triphosphate, ATP, the ubiquitous
energy currency your cells produce to basically make everything work.
Cool. Actually, you know what?
Maybe that's not as famous as I thought it was going to be.
So while we're looking at it this way, here's
one of my favorite facts in all of biology.
Take two phosphates off here and then chain this adenosine together
with a bunch of guanine, cytosine and uracil.
And that's RNA.
Heck, you know what?
Mess with that ribose sugar a little bit, turning it into deoxyribose.
And it turns out that adenosine is adenine.
The letter A in your DNA.
I'll never stop gushing about that.
Your cellular energy currency is just repurposed RNA letters.
Biochemistry is so good at so many things, but one of the most incredible
is how willing life is to just repurpose every single thing in its toolkit
whenever it can.
But anyway, let's get back on track and look at our adenosine
caffeine comparison that similarity between caffeine and adenosine.
That almost feels like an answer to our question, right?
Caffeine is similar to our energy currency, and like
I feel more awake and energized after consuming caffeine.
So are my cells somehow using caffeine as a kind of spare energy currency?
No, not even close.
But this connection to adenosine is actually really important.
So let's get into the real reason caffeine gives you that buzz.
To do this, we'll have to dive a little bit into neurology.
But I'm going to keep this very surface level
because neuroscience can get incredibly complicated incredibly quick.
Caffeine's most powerful effect comes from how it binds to this receptor.
The A2 are adenosine receptor A2.
A is a little protein switch that sits on the surface
of tons of different cell types throughout your body.
The business end of a tumor is this little pocket embedded in the cell membrane.
And this receptors job is simple.
When a specific molecule on the outside of a cell binds
here, its shape will change just enough to relay a message inside the cell.
Specifically, A2 air is a special class of protein
called a Gpcr, a G protein coupled receptor.
I did a whole primer about how they work a while back in my video on vision.
So just go ahead and check that out
if you want more information on the fundamentals of GPCRs here.
Anyway, caffeine is specifically an antagonist of these A2 receptors
meaning that it gets jammed
in this binding pocket without turning on the little switch.
Caffeine is the perfect shape to actually get stuck in here for a while,
so drinking caffeine basically blocks the signal this switch usually sends.
But of course, that unlocks a bigger question
what exactly are we blocking here by drinking coffee or tea?
You know what?
I figured the name gives it away a little,
but A2 receptors get properly activated by you guessed it, adenosine.
And that's going to get us to the way.
More interesting question why on earth is our energy currency?
And literally a piece of our RNA code also a messenger molecule?
And gosh folks, I love this bit.
Let's very briefly touch on your metabolism.
So we have everything we need to understand what caffeine is blocking here.
Okay, so maybe you know this already, but being alive is difficult.
Our superpower as eukaryotes
comes down to how much energy our mitochondria can process.
Making smaller and less dense prokaryotes come off as positively sluggish all day.
Your mitochondria are converting food energy into this ATP currency.
Using the oxygen
you breathe as the final link in something called the electron transport chain.
And again,
I'm shaving off a bunch of critical details here,
but it turns out that this chemical engine isn't perfect.
Things can run hot after a while, and if your cells are forced to perform
at a high level all the time, things tend to break down.
Your mitochondria can end up leaking
all sorts of toxic byproducts if they're pushed too hard.
Things like reactive oxygen species
and other nasty bits that can damage DNA and otherwise blow up your cells.
And this is why some teams are publishing research
that kind of convincingly illustrates how our mitochondria are the main reason
that we and most other animals have a sleep drive in the first place.
We need a guaranteed period during the day where we're basically doing nothing
so we can keep our powerhouses from running too hot.
You know, give those mitochondria a break.
If I can oversimplify things even further, and therefore we get that sleep
drive mostly from the cells in our body that use the most energy.
Can you guess which ones those are, by the way?
Yes, exactly.
It's your brain, your nerve tissue.
Despite only making up 2% of your body weight, on average, your brain consumes
around 25% of your daily energy output.
Life is hard, but consciousness is much harder.
And that's enough context for us to bring this back to our sleep signal.
But first, let's hear a quick commercial segment.
This episode of clockwork has been made
in support of Kitson Co, the coffee and tea powerhouse over a goods store.
If this video makes you want to experience
these pharmacological effects of caffeine firsthand, Keates and Co
has the highest possible quality coffee and tea ready for you to try.
The team at Kitson Co partners with local initiatives in the areas
they sourced their raw ingredients to ensure fair competition
for workers, sustainable farming practices and environmental protection.
And the best part is the profit from Keats and Co directly funds
tuberculosis treatment programs in Lesotho, so you can get that buzz
while sticking it to humanity's most ancient enemy and predator.
Support the channel by visiting
watch clockwork.com/keats,
personal favorite product of theirs is the light roast
Calypso coffee, which is great for pour over,
but you really can't go wrong with any of their products.
But anyway, let's get back to the video.
So throughout the day, the mitochondria and these neurons
are constantly pumping out ATP to power all that brain business.
ATP moves energy around by breaking a phosphate group off
and becoming adenosine triphosphate, and there are mechanisms in place
to further break ATP into raw adenosine utterly phosphate free.
So there is actually raw adenosine floating around in your cells as well.
Throughout the day and throughout the day that's spent,
adenosine starts to build up inside your neurons.
In a perfectly efficient system, ATP would get produced, broken down into ADP
or raw adenosine,
and then get brought back to the mitochondria to get re-energized.
However, no cell is a perfect system, so spent adenosine can't help
but accumulate throughout the day.
Neurons respond to this by pumping that less energized
adenosine into the extracellular space outside their membrane,
and this eventually becomes one of the many sleep
signals that help set and reinforce your circadian rhythm.
As raw adenosine builds up in the fluid between your super active neurons,
it will reach a barrier region and one of the core parts of your brain.
The shell surrounding the nucleus accumbens is. here.
We have a concentration of branching neurons
that are absolutely covered with those H-2a adenosine receptors.
These fellows have a bunch of different jobs,
but the one we care about is the role of regulating certain
groups of neurons, making them more or less active.
When adenosine finally reaches this region,
they'll bind to these H-2a receptors and activate a big signaling cascade
that basically turns off your awake system in your brain.
And feel free to skip this next bit
if you don't want to get too deep into the biochem.
By the way, this is all pretty indirect, but basically the activated a two way
system will turn on this pump gas one which will then vacuum
up as much of this neurotransmitter Gaba as it can.
To again, really oversimplify this.
The Gabba in your central nervous system helps keep your various arousal neurons
active while lowering Gaba levels allows neurons in charge
of your sleep system to take over these two systems.
You're awake
and your sleep signal are basically in a chemical wrestling match all day.
Where you're awake.
Centers inhibit your sleep centers until a switch like these H-2a receptors
push the sleep system into dominance, you know, making you tired and fall asleep.
Therefore, your daily energy burn gradually increase.
Is this sleep signal?
As more and more adenosine binds to more and more adenosine receptors,
which is why it's important that caffeine is kind of a similar shape to adenosine.
By jamming up these H-2a receptors, your coffee or tea blocks
the sleep signal, which in turn promotes the alertness signal
already being received by your arousal neurons.
And that's the main game caffeine is playing.
It doesn't, quote unquote, give you energy.
It simply tips the delicate balance of signals in your brain towards
feeling more alert and more awake and, frankly, more awesome.
That's why coffee wakes you up in the morning
to a jump, starts your awake neurons, which automatically inhibit sleep
signaling, It is very simple and very specific,
which is why caffeine rules as a psychoactive drug.
This really is the primary mechanism caffeine is working with.
Most other substances that mess with your mind, have tons of other
side effects that can get really gnarly or really weird really quick.
Not caffeine though.
And this is also
why coffee and tea can't keep you awake if you're super sleep deprived.
Caffeine and adenosine compete for a spot in these eight two way receptors.
If the adenosine concentration outside the nucleus accumbens is super high,
there just isn't a way
for caffeine to muscle its way in and jumpstart your alertness.
And this is also why more coffee more often doesn't make you more awake.
You might have heard about how your body builds up a tolerance
for caffeine over time, but like, how does that even work?
And this is my favorite part of any one of my videos, where
we've gotten so deep into the cell biology that I get to blindside
you with one of the foundational quirks of being alive.
Here's the thing if you consistently consume a whole bunch of caffeine,
sure, at first you'll block that sleep signal a whole bunch.
But biochemistry and cell biology are all about balance.
No matter what you do to your body,
your cells are going to fight their way back to homeostasis,
back to an equilibrium where you can get enough sleep.
So eventually,
if you keep shoving little caffeine molecules into your A2 receptors,
your body is going to up regulate the way to aging,
which means your body is just going to make more adenosine
receptors, thus diminishing how effective caffeine is.
If you're just going to block all of these targets,
your body is
just going to make more targets until it overwhelms whatever you're doing to it.
I'm serious. For the most part.
You are always in a kind of arms race with your own biochemistry.
It doesn't matter what new chemical or circumstance hits
a cell, that cell will mostly always fight to establish equilibrium around it.
This is one of the core insights I want you to get out of most every video
I make.
For the most part, you are not some monolith set in stone
and trapped in the mold your DNA has set for you.
The world, in a way, talks back to your DNA
and you regulate your way back to baseline any way you can.
silence your sleep signal and your brain will simply listen closer for it.
This is also partially what lays the foundation for caffeine dependency.
Maybe you've been there.
Rely on caffeine too much for too long, and going cold turkey feels just awful.
Suddenly removing caffeine from the equation makes these cells
way too sensitive to the tiredness signal from adenosine,
and that sets you up for irritability, exhaustion, and in my experience,
a spirit shattering headache that outshines any other pain.
Which is why, as always, it's important to slowly ramp your way up
when using things like caffeine and then to even more slowly ramp your way down.
And while caffeine has dozens of other smaller effects,
I think we can take enough away from this small slice of the mechanism.
Frankly, I was going to do a whole thing about how caffeine may have evolved
more as an insecticide and how much can blow up the nerve systems of arthropods.
But luckily, in the middle of me making this video
hankering, I made a video covering that beautifully.
So go watch that video instead.
And I don't have to worry about animating any of caffeine secondary effects
because trust me, it is really hard to talk about phosphodiesterase inhibitors
in a way that anyone will really care about.
Probably in the end, when you think about things like the conversation caffeine
has with your body, it's important to keep in mind that life isn't a noun.
It's a verb.
Living systems are riotously dynamic, never really keeping still
or staying exactly the same across any given nanosecond.
It takes so much effort just to be here, even when this older brew
stops being helpful and starts being a background necessity.
But in learning this, I hope you realize that
basically everything you do is altering your brain chemistry in some way.
Try to hold on to that.
Either way, that's a solid place to leave things.
I really appreciate your time. Thank you so much for being here.
And hey, as always, thank you so much for reaching the end of this video.
You have no idea how much that helps the channel every time you do it.
If you enjoyed this video, I would appreciate it.
If you liked or subscribe to this channel.
One huge way you can help too is by joining us over a Patreon
so you can get access to our awesome September Sticker
Club packs, which is all caffeine, all the time. Let's go!
It's going to be one of the only times
you can be able to get ATP stickers out of me.
Anyway, I'm molecular papercraft.
This month is also awesome as well.
It's my favorite protein photosystem two.
More on that later.
Either way, another way you can support the channel is of course
heading over to watch clockwork.com and joining our newsletter
at the same time, make sure you check out watch
clockwork.com/keats to see all the cool coffees and teas that Keats and co have.
Of course, with this in mind, I gotta know are y'all more coffee folk or tea folk?
Can you comment below?
What are your preferences if you have any?
And I would love it even more if you got really granular with it.
Like if you have a specific tea leaf,
like I've always preferred light roast coffee and oolong tea, but that's just me.
Either way, I would also love to know what you think about these
these shorter kind of fast and newest videos
as I ramp up to a absolutely massive project going over
DNA translation protein synthesis in your ribosomes.
And so any and all feedback is super, super helpful.
Either way. I've talked to you earlier off here enough.
I really appreciate your time.
So as always, like to leave you with peace, love and activated G proteins.
Everyone be well. Thank you so much.
Me.