Your lectures are amazing, Thank you pretty much. you are the best teacher ever. just a note: I think the arrow to R state must be larger where all heme groups are bonded to O2 in sequential model in notes on the board.
You're so amazing sir.. plz don't stop uploading videos to this channel... I saw the last uploaded video was 3 months ago... pls don't stop uploading videos... these are really really helpful
Your videos allows me to take notes while you teach sir, nowadays am kinda the baddest in biotechnology because of you ,thank you and much love from Kenya 🇰🇪🇰🇪🇰🇪
Very thankful for moderately slow explanation♡♡♡♡♡Im biotech- majoring korean who likes English but not good at listening fast English🤣 Deeply thankful for your perfect lecture. Hope you full of happiness☘🍀
I'm not sure I agree with the stated limitations of the concerted and sequential models - if only because I think what you say in the video might be a little misleading. I think the difference between the two models is fundamentally the distinction between an equilibrium between binary states and an equilibrium between a sequence of many different conformational states. The former is what the concerted model proposes, i.e. an equilibrium between only two distinct states, the T and R states, a fact that you yourself seem to state at 1:00 when you say, 'the big point about the concerted model is haemoglobin can only exist in two states'. The changing conformation of one of the 4 polypeptide subunits that make up the haemoglobin is a *concerted* process with the corresponding conformational change of all 4 of the subunits. Which is to say, if one changes, they all do, which is why there are only two states for the whole haemoglobin molecule. The equilibrium is steadily shifted in favour of the R state as more oxygen binds because it's the R state that binds with a higher affinity to oxygen - i.e. it is the state of lower free energy when oxygen binds and so the more oxygen that is binding, the more favourable it becomes to have that conformational state. (That description could be far more mathematical by applying thermodynamics but I think it is unnecessary provided there is a qualitative understanding of Gibbs free energy and equilibrium dynamics). So when you say at 4:43 that, 'according to the concerted model, this structure of this polypeptide that contains the bound oxygen does not change its conformation', I think it is misleading because although it would be accurate to say that the model does not propose a conformational change in that particular subunit *alone*, it does propose that the binding will increase favourability of a conformational change to *all* 4 subunits and this corresponds to forming the R state. This is why the arrow pointing towards the R state gets longer. So, when you say a moment later that in nature we see that, 'when one of the haem groups binds that oxygen, the adjacent haem groups are also affected', and that this is therefore in contradiction to the concerted model, I disagree. The concerted model suggests that all of the other groups are (statistically speaking) all altered completely so that the R state is achieved (or is more likely to be achieved as the equilibrium is shifted towards it) - and this is consistent with your statement. The more I watch the video, the more I do think that this is what you're getting at - but I still think it's misleading. The nuance is introduced with the sequential model which instead does away with the idea that the conformational change in the subunits should all be complete and a concerted process - but instead says that it is incomplete and sequential. The issue I have with your statement about the limitation of the sequential model is actually more of a question: you say that the problem is that when three oxygens are bound to the haemoglobin it is found to more-or-less be in the R-state and not some intermediate. Is that not an issue with an adjustable parameter? Couldn't one suppose exactly as the sequential model does that the binding of the oxygen to one subunit partially alters the conformation of the other subunits, but now add that it does so by exactly a 1/3? So that when three oxygens are bound, the overall state of the haemoglobin now resembles the R-state? I hope this comment was clear.
Hi, although the explanation and clarity is awesome, the concerted model assumes that oxygen will only or predominantly bind to the R state and, upon binding to the R state will shift the equilibrium between the two empty forms, from the T to the R in order to compensate for this binding. This does not change the fact that the sequential model can still occur. Thanks.
We defined all of the circles in the concerted models to be in the R-State but it's this arbrtarly defined, and could be defined however the creator of the model decided? If this is the case could we not simply refine which intermediate groups of 4 were included in the R-State for the sequential model so that the last two intermediate groups were both shown/defined to be primarily in the R-State and the first two intermediate groups were shown/defined to be in the S-State? I guess my question is regarding how the sequential model fails. Isn't it just a matter of redefining what the model shows/defines to be in which state and it solves the only problem that model has? I don't see why we need two models - the concerted model seems to just serve as a preliminary model that is useful to learn in order to more easily understand the more appropriate sequential model that should be corrected to redfine the last two intermediate groups as both being predominately in the R-state and the first two intermediate groups being predominately in the T-state.
very helpful thanks a lot. but according to concerted model when two molecules bind or even one binds it changes haemoglobin to R state. isn't it against the molecular evidences. like we cannot say it totally justify the molecular evidence which shows the R state after binding of 3 molecules bcz it.
Hi, can you please urgently do a video on Adair equation and its relevance to MWC. This would be so helpful, I have an exam so soon and I'm kind of struggling to understand.
@@AKLECTURES a general model exists but is too complex for practical use. see this: www.sciencedirect.com/science/article/pii/002228367490343X?via%3Dihub and page 30 of this: www.nobelprize.org/uploads/2018/06/eigen-lecture.pdf
Great, but why don't we just correct the sequential model with the 3 O2 already being in the R state, name it a new 'correct' model, and call it a day???
How is it possible that under a really specific science video, there's a comment like this one? xD (If this is supposed to be joke it, it went over my head)
Medschool student with a biochemistry exam in 10 days sends you blessings
How's medschool going now fam?
This man is doingg god's work here. No intro, no plugs, no personal info, cutting straight to the chase here and i love it
thankyou so much, you're the only teacher who explained this concept clearly.
Finally, understood these 2 models.
Thank you.
Your lectures are amazing, Thank you pretty much. you are the best teacher ever.
just a note: I think the arrow to R state must be larger where all heme groups are bonded to O2 in sequential model in notes on the board.
You're so amazing sir.. plz don't stop uploading videos to this channel... I saw the last uploaded video was 3 months ago... pls don't stop uploading videos... these are really really helpful
good sir you just saved my grade! praise the lawd! thank you so much!!!
your lectures have helped me tremendously in my biochem class
Your videos allows me to take notes while you teach sir, nowadays am kinda the baddest in biotechnology because of you ,thank you and much love from Kenya 🇰🇪🇰🇪🇰🇪
Very thankful for moderately slow explanation♡♡♡♡♡Im biotech- majoring korean who likes English but not good at listening fast English🤣
Deeply thankful for your perfect lecture. Hope you full of happiness☘🍀
I'm in the same case. A lot of thanks to AK lectures.
thanking God for showing me your lectures
This no joke saved me, such a concise and clear explanation. Many thanks!
Thanks sir. I spent my whole day to understand it..but now it’s become easy to me as like drinking water
You're amazing ! All your videos are really helpful ! Thank you so much for making biochemistry easier to understand
U r best teacher in the world for biochemistry lots of love or prayers for you from Pakistan ❤❤
outstanding ! helped alot ! Greetings from India ! :)
Great job, as always. I really appreciate it... Greetings from Chile!
An IIT, Delhi fresher with his END SEMESTER Exam tomorrow, sends you blessings !!!
Thank u so much sir ...!u r like a galaxy ...and all the students revolves around ......!
Thanks for your efforts sir😘
I'm not sure I agree with the stated limitations of the concerted and sequential models - if only because I think what you say in the video might be a little misleading.
I think the difference between the two models is fundamentally the distinction between an equilibrium between binary states and an equilibrium between a sequence of many different conformational states.
The former is what the concerted model proposes, i.e. an equilibrium between only two distinct states, the T and R states, a fact that you yourself seem to state at 1:00 when you say, 'the big point about the concerted model is haemoglobin can only exist in two states'. The changing conformation of one of the 4 polypeptide subunits that make up the haemoglobin is a *concerted* process with the corresponding conformational change of all 4 of the subunits. Which is to say, if one changes, they all do, which is why there are only two states for the whole haemoglobin molecule. The equilibrium is steadily shifted in favour of the R state as more oxygen binds because it's the R state that binds with a higher affinity to oxygen - i.e. it is the state of lower free energy when oxygen binds and so the more oxygen that is binding, the more favourable it becomes to have that conformational state. (That description could be far more mathematical by applying thermodynamics but I think it is unnecessary provided there is a qualitative understanding of Gibbs free energy and equilibrium dynamics). So when you say at 4:43 that, 'according to the concerted model, this structure of this polypeptide that contains the bound oxygen does not change its conformation', I think it is misleading because although it would be accurate to say that the model does not propose a conformational change in that particular subunit *alone*, it does propose that the binding will increase favourability of a conformational change to *all* 4 subunits and this corresponds to forming the R state. This is why the arrow pointing towards the R state gets longer. So, when you say a moment later that in nature we see that, 'when one of the haem groups binds that oxygen, the adjacent haem groups are also affected', and that this is therefore in contradiction to the concerted model, I disagree. The concerted model suggests that all of the other groups are (statistically speaking) all altered completely so that the R state is achieved (or is more likely to be achieved as the equilibrium is shifted towards it) - and this is consistent with your statement. The more I watch the video, the more I do think that this is what you're getting at - but I still think it's misleading.
The nuance is introduced with the sequential model which instead does away with the idea that the conformational change in the subunits should all be complete and a concerted process - but instead says that it is incomplete and sequential. The issue I have with your statement about the limitation of the sequential model is actually more of a question: you say that the problem is that when three oxygens are bound to the haemoglobin it is found to more-or-less be in the R-state and not some intermediate. Is that not an issue with an adjustable parameter? Couldn't one suppose exactly as the sequential model does that the binding of the oxygen to one subunit partially alters the conformation of the other subunits, but now add that it does so by exactly a 1/3? So that when three oxygens are bound, the overall state of the haemoglobin now resembles the R-state?
I hope this comment was clear.
thank you for clearing up the issue of confirmation shift in the concerted model
If you know all these already, why are you watching the video?
Team the guy who almost hit Bela with a car lmao
great video ! if only teachers explain things the way yo do the world would be a better place
thank you so much for such amazing lecture...😚
your lectures are awesome!!thank you so much.
your videos help so much!
Hi, although the explanation and clarity is awesome, the concerted model assumes that oxygen will only or predominantly bind to the R state and, upon binding to the R state will shift the equilibrium between the two empty forms, from the T to the R in order to compensate for this binding. This does not change the fact that the sequential model can still occur. Thanks.
It was very helpful. Best explanation
Amazing video.
Lecture so good ambatukam
Got a video on everything!
Phenomenal explanation!
Great video, you did a much better job explaining this than my professor did. #sanfordsimon
This was simple and straight to the point.
Thank you very much!
you're welcome! :-)
Thanks for lecture
wonderful
Well-explained
I love and respect you so much 💚💚
This video is very helpful!
Should the last arrow in the sequential model be favoring the R state more than the T state? Great video btw!
Love your videos man
Will you please do a video that explains Adair's Equation? :(
crystal clear
We defined all of the circles in the concerted models to be in the R-State but it's this arbrtarly defined, and could be defined however the creator of the model decided? If this is the case could we not simply refine which intermediate groups of 4 were included in the R-State for the sequential model so that the last two intermediate groups were both shown/defined to be primarily in the R-State and the first two intermediate groups were shown/defined to be in the S-State?
I guess my question is regarding how the sequential model fails. Isn't it just a matter of redefining what the model shows/defines to be in which state and it solves the only problem that model has? I don't see why we need two models - the concerted model seems to just serve as a preliminary model that is useful to learn in order to more easily understand the more appropriate sequential model that should be corrected to redfine the last two intermediate groups as both being predominately in the R-state and the first two intermediate groups being predominately in the T-state.
I got a question: but do the two states (2nd and 3th) in the sequential model effectively exist in nature?
really helpful! love Your videos!
Best Regards,
Undergraduate Biology student
Felicia Minnich thanks! :-)
after going through my course few time than wikipidia (in 3 languages english, french and arabic) it's actually that simple..
Hey there! Great video! Could you explain the relation of hill'd number with the allosteric enzymes? That would be awesome!
Thanku so much
nice video buddy
Thanks
very helpful thanks a lot. but according to concerted model when two molecules bind or even one binds it changes haemoglobin to R state. isn't it against the molecular evidences. like we cannot say it totally justify the molecular evidence which shows the R state after binding of 3 molecules bcz it.
You’re the best thanks👍
Thanks sir
thank you very much.. helped me a lot..
Hi, can you please urgently do a video on Adair equation and its relevance to MWC. This would be so helpful, I have an exam so soon and I'm kind of struggling to understand.
I can not thank you enough!
you are a godsent
thank you!!!
awesome stuff! thanks dude.
闫雷 you're welcome! :)
Thank you so much.
Thnku sir ...
Amazing
so why not there's a model that combines the two together?
+Tein Luu Good question! Let me know when you come up with one!
@@AKLECTURES a general model exists but is too complex for practical use.
see this: www.sciencedirect.com/science/article/pii/002228367490343X?via%3Dihub
and page 30 of this:
www.nobelprize.org/uploads/2018/06/eigen-lecture.pdf
Awesome!!
Great, but why don't we just correct the sequential model with the 3 O2 already being in the R state, name it a new 'correct' model, and call it a day???
great , thnx doc :)
genius
You saved me 😅
This is very vaguely explained
👍👍
goated
So imagine when the 5G happens and spins the O2 So it's unable to bind to Haemaglobin... Buteyko breathing.
How is it possible that under a really specific science video, there's a comment like this one? xD (If this is supposed to be joke it, it went over my head)
Good content but man you speak slow. I had to put it on x1.25 speed because of how slow you speak my dawg.