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'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-turbine experts in their own right-tend to have no knowledge of the most novel turbine around! I'd say they're missing out ;)

How the hell am I discovering this only 3 years after the upload? First time I understood how ATP works as an energy source!

"A cool little middle finger raised up to entropy and chemical equilibrium." Ah, I see you fight the good fight.

It's not a middle finger to entropy; this whole chain of energy transformation is a system that surfs the gradient of the universe's ever increasing entropy.

This is why i add ATP to my morning coffee.

1:51 "it takes a lot of energy to be alive" - I feel that bro

“A cool little middle finger raised up to entropy and chemical equilibrium” Give this man a Nobel 😂

It's bloody criminal how few views this video has. You deserve more. Your product is energizing and fundamental.

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...

As an industrial automation guy, I see a lot of similarity between the processes I deal with and biological processes like this.

"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!

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.

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.

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.

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!

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 :)

This was honestly the most helpful explanation of ATP synthase that I could find on the Internet. Thanks a lot!

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'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 KZfaq 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!

Okay, seriously, your animations are soo good and I love your presentation style in this one!

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)

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'

The ATP synthase is powering my brain for it to understand it. I have known in crude terms how the synthase works, but it still amazes me. This and the transport enzymes walking along microtubules are among the most intriguing things in microbiology I know of.

Biology is technology.

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

I started watching the video thinking there is no way I am sitting through a 20 minute video on ATP synthase. I ended up watching it twice over. Genuinely thank you and very well done for putting information and presentation of this calibre for us mere mortal to see 🙏🏼

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 like that you brought us out of the o-chem focus to make a very interesting point: "[People make dams etc. to] Harness and distribute energy with the exact same principle." I think it's also very interesting to add: with almost all of those things needing the exact same weird material to do their work: water. Liquid water flowing through the turbines of a dam. Or high temperature steam flowing through turbines in so many other kinds of power plants.

As a physicist it took everything I had to resist getting triggered by the magnets/electrical charges conflation in the section about water.

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!

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.

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

Wow. I just found your channel from this video and I'm very impressed with the quality of this. Thank you ❤

WOW, YOUR METHOD IS AWESOME, I'll never forget this process, once a person fully understands a concept, it's forever. Thanks for your dedication in furthering our students in America, " Making America Great"

This was unexpectedly incredible. The ending swept me off my feet. Thank you so much!

Thanks John green for suggesting this channel . That guy keeps helping my brain . Animations are slick !!!!

PERFECT video, you have a new subscriber! My son who is studying biochemistry in high school showed me this video and introduced me to your channel. The content is classroom ready, it should be used in schools. Your channel is massively underrated. Your content deserves much more attention. Keep the great videos coming!

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.

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.

the ending was really beautiful, thank you!

I'm now finding the beauty of smaller channels You seem to process huge chunks of information in a unique way - i have the SAME CONVERSATIONS in my head Thank you for discussing these concepts with me in a way that i understand How can i donate to you while i binge watch

This is so incredible. I wish you were still making videos!

Fascinating. Exceptionally well explained.

This is such intricate and detailed video ,great video. Chanel is so underrated

I was not expecting such nice reassurances at the end of what i thought was a good background noise video :,)

Super cool video! I really wish stuff like that was available when I was at the school age, but tis' never too late to learn. Seeing mechanisms in motion makes it so,so much easier for all visual learners.

Lovely vid, you explain it very passionately!

This is INCREDIBLE! You deserve way more subs!

VERY good video! I'm an EE with lots of science interests and this biochemistry video is captivating. In the context of the evolution of life, the vast stretch of time needed for such complex mechanisms to arise makes a great deal of sense.

blogbrothers sent me and I'm so happy they did --this is great!

you have such a soothing voice and talk about really interesting things

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.

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.

I wanted to take a moment to express my admiration for the exceptional work you did in this video. Your passion for the subject is truly inspiring.

Heyy, this is an awesome video and you explain things very intuitively and meticulously!! Earned a sub within a few RPMs!!!!

Really excellent video. Thank you

This is beautiful. Thank you!

Thank u so much 4 making this knowledge available and so easy to understand.😊✌

hey thanks for the great video! nice little words from you at the end :)

Thanks so much, very informative!

What a gorgeous machine! And what a great channel!

Thank you for help us understand the enormous complexity that is needed for life to exist.

This is fantastic, I love your use of the words inner cosmos ;)

I just found this channel and i have to say ive liked every single video Fantastic work! You deserve millions of views

This is so in depth and illustrative, I love it!

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.

Excellent Explanation of the Mitochondria. The best I have ever seen about this subject. Kudos to you. Excellent explanation beautifully animated. Thank you.

Excellent work. I hope bio students appreciate your work because I sure wish this was available when I was a student.

Such incredible work! Thank you so much for your efforts in producing at such a spectacular level!

when i first learned about this in 9th grade it blew my mind. So much so that i still think about how my body is full of spinning machines all the time. Im glad im not the only one who finds this mechanical action fascinating.

This takes me back to college! Also the ending was so inspirational. I love learning about the small details of chemistry. Water is underrated!

After the last comment I decided to sit, drink, eat a snack, make sure all my engines firing on all cylinders and start working on my thesis. Subscribed.

I'm speechless, this has to be one of the most amazing videos I have ever seen! I'm a med student, (and it pains me a bit to recognize this😅) but I've always had a hard time understanding Biochem. When classes come to an end, I think I get the concepts, but they never fully click to me. But this video? Gosh! The stunning animation, the complex concepts explained with ease, and the passion in your speech... a 20-minute masterpiece! Thank you SO much for making this content. I finished this video with the feeling I believe to be the most beautiful in the world: hunger for knowledge. Sharing with everybody, because this quality deserves to be recognized! 🤍

Amazing as always.

I'd love to be able to create these little mechanical machines. They're so cute and being able to pull on specific sides of a molecule seems like a cool skill

Incredible video info (from my view- I didn't study bio) and the last part was very good and something that a ton of people need to hear, and listen to. Me too probably.

Dude, it's absolutely criminal that you have 10k subs. I love this channel biggly.

I'm really enjoying these videos. Keep up the great work!

So few view for such a stunning video! Amazing work!

When I learned about it, it was a vague "the protons move through ATP synthase and that causes ATP". I never knew this level of detail.

amazing work !

Its even more mindblowing to think that this complex mechanism can be arranged by just billions of years of random motion of atoms. Such majestic order come out of disorder.

I very much enjoyed that deep breath and body actualization... :)

Very excited to see this type of content coming with this style of animation. It's fantastic

Awesome, awesome video. Informative, funny, and inspiring. Nice animations too.

Amazing! Thank you

I didn't realize ATP Synthase was a motor. I remember trying to learn how cilia and flagella work without muscles and seeing the insanely complex motor proteins driving them. I understood absolutely nothing, but I was blown away by the complexity, and how similar it is to a real motor, with a stator, rotor, etc. I WILL understand how they work one day. Even if it takes me 10 years. (I'm self taught for 25+ years).

Thanky for the vidja and the FINE animation helping recount the Calvin and Krebs cycles. VERY helpful for refreshing something I used to review and use daily but have not for 30+ years. Subbed. Peaceful Skies.

Thank you for this

Brilliant, many thanks

came to study for a biochem test, left with a tear. thank you

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

Instant subscription. What an incredibly video that really does a good job of centering the awe and reverence of the natural world that I believe should be foundational to a love of science!

Your video is so great, that no one disliked it! I didn't know I want to understand biochemistry.

That feel when you realize your body generates six times more energy by volume than the sun.

Fantastic animation!

Absolutely under rated channel. Bout time algo started rewarding you

I guess the algorithm has blessed you. While scrolling through comments I see multiple people mentioning seeing this channel for the first time, and im right there with them!

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.