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- เผยแพร่เมื่อ 22 ธ.ค. 2020
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ATP Synthase is one of the most important and fundamental machines that gives life it's incredible powers. Looking at it from the chemical level will give you even more respect for just how much work it takes for you to even read these words right now.
Sources are cited in this ever-growing Twitter thread: bit.ly/synthasesources
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This channel is dedicated to sparking your curiosity about biochemistry, not to being a definitive resource. To help you continue your biochem journey, I'm really excited to partner with Biocord , a Discord server dedicated to bringing together biologists from around the globe! Join the conversation with over a thousand life sciences professionals and enthusiasts here:- / discord
All music is by Jeremy Blake( / redmeansrecording , released on the TH-cam Audio Library.
Intro music: Let's Go Home (bit.ly/rmrlgh)
Outro music: Lost and Found (bit.ly/rmrlnf)
The style of this video was largely developed based on tutorials by Ben Marriot: (bit.ly/posterizethis)
I've been following this channel for a couple of months, since I saw your first post on Reddit, and I'm really impressed by the fact that you're still putting out these well researched videos with stunning animations! Because I think your goal is to give accurate and more detailed accounts of these molecular mechanisms than what could normally be found in a standard biochem textbook, I have several observations nitpicking things that I think could have been explained more clearly. I hope this helps someone who wants to go a bit more in depth with this fascinating topic.
0:32 If I counted correctly, the c ring drawn here seems to be made out of 12 subunits. In reality, the chloroplast ATP synthase can actually move 14 protons per rotation and it's important to note that the stoichiometry of the c ring varies from species to species (from as low as 5 to as high as 15). Generally the mitochondrial ATP synthase c ring is smaller than the chloroplast equivalent and pumps 8 protons with every full turn.
1:35 I think it's important to clarify that the job of ATP synthase is not only to synthesize ATP, the mechanism described in this video is completely reversible and the enzyme can work as a ATPase which pumps protons against their electrochemical gradient by hydrolyzing ATP. This process is especially important for some species of bacteria which in certain conditions need these proton gradients to power other mechanical processes such as movement (flagella uses a similar rotor mechanism as ATP synthase) or the transport of metabolites. However, we can also see this in the human cells, type V ATP synthases are found in the membrane of lysosomes where they acidify the interior of these organelles which are later used for digestion.
2:06 ATP to ADP is not the only energy releasing reaction used by cells, ATP can also be hydrolyzed to AMP + pyrophosphate (e.g. amino acid activation for protein synthesis, synthesis of cintrulline from argininosuccinate during the urea cycle). Moreover, other molecules similar to ATP (e.g. GTP) are sometimes used to power cellular processes.
2:35 I don't think saying that you get as many protons as possible crammed into the lumen is correct. The pH inside the lumen is around 6, so the proton concentration is "only" 10 times higher than what you see in the cytoplasm, but there is not physical reason which prohibits the pH to go ever lower than this. However, the size of the proton electrochemical gradient is capped at a specific value because at higher concentrations the protons would be leaking through the membrane at very fast rates, making the whole process too inefficient. (proton leakage means that the protons move from one side to another without passing through the ATP synthase, so their potential energy is not transformed into useful work for ATP synthesis)
2:52 As I said above, the concentration gradient is not huge, in thylakoids is at most 2 pH units wheres in mitochondria is about 0.4 pH units. In the case of mitochondria is important to say that both on the inner and outter side of the inner mitochondrial membrane there are buffer molecules which keep the pH relatively constant. If the pH were to drop inside the mitochondrion, this would lead to the denaturation of a bunch of enzyme whose catalytic activity is notoriously known for being very pH sensitive. Therefore, the energy stored in the proton gradient in this case is predominately in the form of a membrane potential (the interior of the mitochondrion is more negatively charged than the exterior), so similar to how a capacitor works. In thylakoids the opposite is true, the concentration gradient is more substantial, but the electrical component of the electrochemical gradient is reduced by the movement of Mg2+ and Cl- ions which equilibrates the charge difference between the lumen and the stroma.
5:36 It's Fo, not F0; "o" comes from oligomycin because initial experiments showed that oligomycin inhibits the function of this complex. F1 gets its name from the fact that it's water soluble and it was present in the first *f*raction isolated.
10:00 Arginine also has another important role, because of its positive charge it prevents protons from moving directly from the inner half-channel to the outer half-channel. (positive charges repel each other)
11:07 The central stalk is not entirely represented by the gamma subunit, there are also other proteins at the interface between the gamma subunit and the c ring. In mitochondria these are the sigma and the epsilon subunits; in Eubacteria there is only an epsilon subunit.
As you can tell, I really love this topic and I want to end this comment with several questions about ATP synthase which still stand unresolved. I think it's important for people which have heard for the first time about ATP synthase to know that this is a field with ongoing research.
Why do we see different c ring stoichiometries between species? How is the rotational movement transmitted from the c ring to the central stalk? If the central stalk rotates in steps, how is the energy stored between intermediary phases?
I am blown away by this! This is the exact kind of feedback I'm always looking for. Thank you so much for taking the time here--I cannot express enough how much I treasure this!
@@Clockworkbio I'm very glad to hear this. I'm definetely looking forward to the next video, keep up the good work!
As a side note, I think the most difficult part when approaching this topic is the thermodynamics describing the proton electrochemical gradient. I think it would be cool to break down this a bit and talk about the electric and concentration component of the protonmotive force. If you plan to do a series about the mitochondrial respiratory chain I think it could fit well with that.
You seem to understand this pretty well so Ill ask you: I still dont 100% understand where the force comes from that pushes the ring. Is it the bending of the helix which, pushing against the two walls of the membrane, pushes the ring?
He reiterates in the video multiple times that its "the chemical gradient pulling the ring" but that sentence doesnt really make sense to me...
If its a pulling, it has to be electromagnetic force between two parts (unless its gravity, the strong, or the weak nuclear force but Im pretty sure its not :P ) so what to things are pulling on each other?
@@Lacksi12 You are correct that it is an electric force. The protons repel each other (positive charge + positive charge = repulsion), so they will spontaneously flow from the low pH side (more protons) to the higher pH side (fewer protons). Membranes are mostly non-polar, so the protons cannot spontaneously cross, which forces them to travel through ATP synthase.
It works in reverse gear too! Amazing.
I'm an aerospace engineer. I live and breath turbines. You'd be amazed by how many of my peers have never heard of ATP Synthase. These peers of mine-turbines experts in their own right-tend to have no knowledge of the most novel turbine around! I'd say they're missing out ;)
Gives whole new meaning to turbomolecular pump..😂
Do you know ORCs pretty well?
How the hell am I discovering this only 3 years after the upload? First time I understood how ATP works as an energy source!
Honestly--it's the best time to meet the channel. Everyone else had to wait years for season 2--you're only going to have to wait about a month!
I'm in the same boat. I was just suggested this video. Seeing that there were no new videos after 3 years, I thought it was dead.
I'm glad to hear there will be another session😊
The algorithm works in mysterious ways. Just got pushed to me as well.
"A cool little middle finger raised up to entropy and chemical equilibrium."
Ah, I see you fight the good fight.
Thank you so much for giving me and my goofy videos ~18 minutes of your life and making it all the way to that teeny little hot take.
It's the only fight, comrade. We'll lose it, but we'll spend whatever slice of eternity we get beating back that current as far as we can.
If you're not a Writer,
You should start.
fuck entropy and chemical equilibrium all my homies hate entropy and chemical equilibrium
Are you implying that life tends to decelerate the increase of entropy? I always assumed it accelerated it globally, even if it maintains lower entropy internally.
@@cerocero2817 Entropy supposedly always wins...
But during the tussle between nuclear binding energy escaping a giant gravity fusor, and getting partially slowed by a tiny mote of molten rock-jelly...
Where even more trapped binding energy and thermal energy is also trying to escape to the equilibrated suburbs of the void....
We find ourselves these little systems of what are really Gibbs Free Energy Pirates.
Life.
We can't exist without a pre-existing unstable system flowing down the Entropy gradient. But we hijack some of that flow, and start converting that chaos in progress into really weird islands of order.
Like ATP Synthase.
And even stranger, these little G pirates started RECORDING assembly instructions for these cunning little islands of order, first on linear polymers, then on dead carbohydrate corpses, then on server racks.
Kinda like using Shannon Entropy in a judo flex against Thermodynamic Entropy.
Big 'ole Delta S is still the heavy odds favorite in this ring, but us G Pirates are making up moves faster than ever.
“A cool little middle finger raised up to entropy and chemical equilibrium”
Give this man a Nobel 😂
I've been actively looking for this for years... And it has been around for 3 years??? Oh man... You chanel is gold! I'm going to watch all I can and if one day you want to continue, I'll be glad to keep watching and liking.🤗🤗
You've made a great job, and it's a shame TH-cam isn't recognising it... As I said, I wanted this but I didn't find it... I'm a biochemistry graduate now and I understand how it works, but never knew the mechanics behind. Now this hunger is satisfied, so thank you!
This is why i add ATP to my morning coffee.
I know you're joking--but they actually give you doses of ATP for certain kinds of heart attacks and cancers! Are your biochemical processes shutting down? Screw this, science will straight up REBOOT you with an ATP injection!
So creatine?
(you cannot eat atp its not bioavailable regardless of what suppliment companies say)
@@ToniMorton well creatine isn't really ATP, I think it just helps ADP recover back into ATP as far as I understand
As part of a cellular phosphate battery, ATP reserves AND creatine together form all your phosphate energy, after which other energy reserves need to be used to recover ATP, so yeah
1:51 "it takes a lot of energy to be alive" - I feel that bro
Miraculous how "Let there be Light!" was actually all of our 'birthday.' Love the idea that the plants all around us peform this miracle every single second of every single day: transforming ENERGY (sunshine) into SOLID MATTER (gluscose). And merely eating that "sunshine" (e.g. an apple) allows our bodies to perform photosynthesis in reverse: matter back into energy... Life.
Even with all that MIRACULOUS stuff going on every moment of every day, your illustration of precisely how MECHANIZED it all is, is mind-blowing on a whole other level.
We ARE wondrous, indeed. We ARE stardust... We ARE beautifully made.
It's bloody criminal how few views this video has. You deserve more. Your product is energizing and fundamental.
One thing that I find interesting is that this isn't really just a middle finger to entropy- this process helps to *accelerate* entropy. Sure, we take some disorder and make order out of it, building structures and powering our brains and bodies. But fighting against entropy takes energy, losing more and more along the way. Think about how much slower energy is consumed and transformed on a place like the moon, an inert rock, compared to the Earth.
we are entropy engines
"This is only the beginning of our biochemical journey together." Damn. Almost got chills. Can't wait to see what else you've got in store for us!
And once again--thanks so much for being such an important part of guiding that journey! I hope you like the video about Nitrogen Fixing and also hope I do a decent job tackling methanogenesis later this year!
This is one of the first times I have had to pause a video... think about how mind blowing is what I just watched... and then keep on going.
You should have millions of subscribers...
Thanks for taking a second at the end to reflect on the profound relationship we have to this information. You eloquently summarized why I like learning about these things. It's the closest thing I have to what others would call a religion.
8:15 - there's a simple explanation why one would call aspartic acid an aspartate: it's in ionic form, so it can be reffered to as aspartate ion (of course, it is linked with the residual protein, but nonetheless)
This deserves so much more attention than it has. The wuality of animation and explanation here is amazing. A wonderful refresher to the content i studied in biology and a much deeper exploration of the mechanical complexity of it all!
This was honestly the most helpful explanation of ATP synthase that I could find on the Internet. Thanks a lot!
As if the idea of a molecular turbine wasn't cool enough, I just happened to be nostalgic about the video game Syberia now, and it has a lot of clockwork machinery in it. For example, there's a fully mechanical robot (an automaton, he would correct me) who is a prominent character and one of the most endearing ones, too. Thanks to this video of yours I feel extra affinity for him, since we all share some of the same machinery :)
I developed the concept and aesthetic for this channel across ~3 years. I eventually landed on these pastels and paper cutouty style.
It was only now--at this moment of reading this comment--that I realized I could have made steampunk explanations for biochemistry.
I will never forgive myself for this oversight.
@@Clockworkbio This style is great and original - semi-paper, semi-vector. I particularly like the electrons
I had biology in my freshman year but due to online classes just read enough to pass. This is just incredible illustration! Got yourself a new sub.
Thanks so much! I hope this gives you a little inspiration to push further! The more you study--the more incredible it becomes. Just takes a little while for it to all click. It's SO VERY worth it though!
When I took my first biochemistry class in undergrad I was blown away, I was in awe of the intelligence of the human body. Thank you for taking the time to go into such detail, this is outstanding! I didn't catch where you mentioned how many RPM this can get up to and can you comment on what determines how fast they pump? I imagine pH has to do with it and do you know how toxicity and ROS interfere with this? Can you discuss how water structure effects this, maybe you already have? Thanks again, Well Done!
I believe many people have read about ATP synthase on bio textbooks but are left wondering how protons actually turn the Fo subunit and how the turning is used to synthesize ATP. This video is exactly what I needed.
Thank you so much for the great work.
Lovely synopsis of entire ATP synthase process. Thanks R_M
I know you made this video several years ago, but I thought I'd let you know that folks out there still finding it and enjoying it. This is one of the best vpapers on ATP synthesis that I've ever seen. Fantastic work... Liked and subed. LoL
blogbrothers sent me and I'm so happy they did --this is great!
I'm so glad you're here--and I really hope I keep making videos that are a good use of your time! Thanks so much!
@@Clockworkbio I got sent here from vlogbrothers too- your videos add the perfect amount of detail to my A-Level Bio course in a way that makes everything more contextual and way easier to recall! Thank you!!
Loved it! My cat, too. You could double-advertise your channel as science AND cat-friendly lol He was enthralled the whole time. 'Science videos for clever cat owners'
Yo I genuinely thought my cat was just weird for like, ALWAYS watching while I'm animating these! I need more data. We gotta find more cats!
Kinda weird to be reminded that an observer would think I’m being “unproductive” when I feel like learning visually is a pretty productive use of my time. I loved this vid (and series so far) other than that though!
I work as a TA in a university biology course, and I absolutely cannot wait to share this with my students!! This is both the most comprehensive review I've seen of ATP synthase AND the most clear, concise, and approachable explanation I've heard. I can't wait to watch more of your videos!
I lol'd at 'concise'. But thank you so much! This one was a doozy to make and I was super worried I went too in-depth on it. Excited for you to share it with your students--I really hope it helps!
So, I remember learning about ATP around age 13, more about it at age 15.
But age 13, that was pivotal, that was where I started to understand a little more about human metabolisms, and that mine was somehow different.
I now know my difference is Glycogen Storage Disorder type 5.
When I was young and in shape, I noticed I had a very hard time starting. I explained it essentially as having a slow starting aerobic cycle, and not enough ATP to bring me to it.
It does leave me with some curiosity though as to where my muscle energy comes from when I'm not eating ketogenically. How my body finds and moves and makes energy, and how I might improve that efficiency.
When humans can micro manage chemical compounds to create nano motors, than efficiencies and power output for all things mechanical will be revolutionary. I know some research is on going but this is truly the holy grail for harnessing the earth's materials in the most ecological manner.
Thanks John green for suggesting this channel . That guy keeps helping my brain . Animations are slick !!!!
3 years later and YouTubr finally recommends me this gem. Love it❤
Perfect timing too-season 2 is just over a month away!
Okay, seriously, your animations are soo good and I love your presentation style in this one!
Hi my name is clockwork and I am TERRIBLE at responding to comments. Thanks so much for your lovely feedback as always! I'd still trade the animations for your perspective in an INSTANT
One of the fundamental aspects to the magic of life is the fact that it solves many problems through energy and or compartmentalization. This is a huge example of the latter. Great video. Will be waiting intently for more
Thanks so much! Got a fresh one coming for you in the next 24 hours!
Just did a project on this protein. It works much more efficiently than the most powerful vehicle engines ever engineered by many folds. It’s mind boggling to learn this.
very good work by you. You are going pretty in depth about this topic but still process it in a way that makes it pretty easy to understand. keep up the good work.
This is beautiful. Thank you!
The poetically beautiful ending in this video, was literally enough, for me to use my atp, and hit the subscribe and like button. And it actually made me feel better about myself. Thank you... Genuinely. Thank you.
Absolutely under rated channel. Bout time algo started rewarding you
This is the best channel EVER!!! I still am wondering how someone can explain such a complicated concept so simply, go in so much detail and instigate such a curiosity and make us so emotional at the end as if it is a movie!!!MASTERPIECE
This is INCREDIBLE! You deserve way more subs!
Thank you for this
I just found this channel and i have to say ive liked every single video
Fantastic work!
You deserve millions of views
What a gorgeous machine! And what a great channel!
This was the best way ive ever seen this presented. Bravo sir. I hope teachers use this in biology class.
And what an ending. Seriously. Thank you. I love when people share the moments where they remember their humanity, and that they are a dynamic process in the universe, just as valid and deserving as every single other process.
I feel that way when I remember that every mathematical field is happening now, all around me. I'm touching them but I only know it esoteric and existentially.
Lovely vid, you explain it very passionately!
Excellent work. I hope bio students appreciate your work because I sure wish this was available when I was a student.
This is so in depth and illustrative, I love it!
And if I had the talent to sound design as well as you do--I would be LITERALLY UNSTOPPABLE. Thanks so much for taking the time to watch this!
I'm really enjoying these videos. Keep up the great work!
Trying really hard--thank you so much! Hope I can keep up this level of quality.
Dude, it's absolutely criminal that you have 10k subs. I love this channel biggly.
Such incredible work! Thank you so much for your efforts in producing at such a spectacular level!
Thanks so much! I wanted to make sure the amount of effort I put into the video at least honored the INSANE amount of effort it took to discover the structure of ATP Synthase in the first place. The subject deserves even more effort than this--I just had to publish at some point.
As an industrial automation guy, I see a lot of similarity between the processes I deal with and biological processes like this.
Thank u so much 4 making this knowledge available and so easy to understand.😊✌
Very excited to see this type of content coming with this style of animation. It's fantastic
Took me a good long while to develop--so I'm really excited that it works for this genre. Thanks so much for your feedback!
These videos of yours are incredible!
You haven't said to breath out, i'm still here 10 minutes in waiting. Got bored waiting, started rewatching the vid. Tell me to breath out though
rip
Every time I'm exposed in some way to the absolute beauty of this system I am blown away.
Thank you! I am a physician and am absolutely fascinated by biochemistry and physiology, but I have never heard such a helpful description of how ATP is created.
Amazing! Thank you
Awesome, awesome video. Informative, funny, and inspiring. Nice animations too.
Wonderful video
Your video is so great, that no one disliked it! I didn't know I want to understand biochemistry.
Absolutely astounding. 😊
Man, this is good. We need more!
Thanks for answering the proton question, I've been wondering 😂
I always used to hate molecular/cellular biology, just because they would always stop at the part where they simply said it was a rotor turning the synthase. Once I got to a class where they actually begun explaining how these charges lead to conformational changes in proteins it all just became so incredibly fascinating. Something like learning how protein coats help bend and bud vesicles just floored me. So incredibly cool.
Your video was excellent, I can NOT wait to see what else you have. Immediately shared with my nerdy group chat, immediately subscribed.
Such a great video. Animating
It must have been rough lol. Great work 👏
Excellent Explanation of the Mitochondria.
The best I have ever seen about this subject.
Kudos to you.
Excellent explanation beautifully animated.
Thank you.
Clockwork you effin rock and I love you.
very neatly made
I very much enjoyed that deep breath and body actualization... :)
came to study for a biochem test, left with a tear. thank you
So few view for such a stunning video! Amazing work!
You blew my mind.
Amazing work. There is no way this channel won't blow up. That is a >1mil subs level of content creation right there.
Hey that means a lot--thanks so much! I'm working really hard to make sure this channel gets there eventually! I'd love it if you could share this video wherever you're able--that'll help build the momentum we need to blow this up!
Found this video researching ATP and the Electron Transport Chain. This is the BEST explanation of the way this system works of all of the dozens of explanations I have seen. The actual MECHANICAL BENDING of the structures in the molecule spin the one part and provides MECHANICAL ROTATING Energy to create ATP!!!! My mind is blown.
As far as the re-arrangement of atomic configuration enabled by the flexibility of chemical bonds can be called mechanical in the classical sense. Otherwise (quantum-wise) everything is mechanical...
Most of the proteins "just" changes it's "SHAPE" to achieve some function: in the end all of them resulting in (in)directly in the creation or destruction of some bonds (not necessarily the covalent type). It's the context which makes sense of them though...
Amazing description! Thank you...i finally understand after all these years...hahah
impressive video !!!
This youtube algorithm... first time recommend this video for me!
Very meditative
Rad animation! I love the idea I have an "inner cosmos"!
This is so weirdly wholesome, I love it!
holy cow this is fantastic!!
Thank you so much! It's so cool being in the same creator community as you! I hope this year is filled with growth and boundless brassica facts for both of us!
The thing you said at the end was so cute and nice.
Really love this channel
thanks so much!
holy wow this, this isnt a video with 1M+ views?? this work is beautiful!!
Channels like this are always a slow burn. Happy to put in the work--especially since I'm hitting a wider audience now. Season 2 drops in June and will only push things higher!
wow this is so interesting!
what a hidden gem this is incredible
This channel is an absolute work of art! Everything: animation, research, presentation, all perfect. Thanks for sharing it with the world!
I mean, I feel like it could be better--but I'm just the most "perfect is the enemy of good" person I know--so I really appreciate your encouragement!
The thing is working like an atomic scale electrostatic motor. It would be fun to make a mini motor of similar size that uses carbon nanotubes and electrons using MEMS techniques. ❤
deep beautiful insights here. both biochemical and philosophical.
i wonder if there is just enough atp all over the place or do quantum mechanics allow those molecules to appear where they are needed most??? otherways you have 390 of them clogging the entries for adp and p every second...
Came here from John Green. REALLY NICE VIDEOS.
That feel when you realize your body generates six times more energy by volume than the sun.
Fantastic
These animations are looking so good! Awesome library you're building
I love how it took me 8 months of pure effort to finally earn a comment from one of the coolest science communicators I know--and THEN it took me a month to respond to them. I'm just so good at this, y'all!
(no seriously--thank you so much for the comment! Really excited to keep growing this library as big as you've grown yours!)
Biology is technology.
Thanks so much! Are there different forms of ATP synthase used by types of organisms? How on earth did this thing come into being, I.e. I wonder how the components evolved and came together. I heard that receptors that allow sodium and potassium to pass in and out of the cell by changing shape may provide a clue about the origins of such mechanisms. Astonishing. Thank YOU for making the video, watching it was a great pleasure and inspiration.
You are at dead end off evolution theory
@@boryskrzeszewski4484huh?
I have studied this from book but I have never studied this before in this incredible way😍🤩❤👏
Gorgeous.
You made it so much more interesting than high school chem
Great videos. I think you could dial down on the meta talk though - "we would be stuck here for an hour", etc.
Ima bout to watch every vid this guy has.
Dang, I'm about to reply to every comment this guy posts.