Explain: Oxidative Phosphorylation

[stone bramble]

Explain the process of oxidative phosphorylation, highlighting the roles of the electron transport chain (ETC) and ATP synthase. Include a discussion of the significance of the proton gradient, the chemiosmotic theory, and the overall efficiency of this process in cellular respiration.

[sudden thistle]

good luck people

[ornate shale]

free

[soft tree]

Things do a thing with a thing and it makes a thing

[signal kelp]

not me thinking abt this QOTW at 1am to try and come up with some base answer

[quick slate]

Because I don't really have the energy to look this up, I'm going off literally years-old memory and going to invoke the Cunningham effect: that my somewhat wrong explanation will induce people to respond with corrections. Please do not depend on this to pass your cell bio exams; thank you!

Oxidative phosphorylation is the final step in the textbook model of cellular respiration. All known organisms can extract energy from glycolysis. Certain organisms can continue this catabolism, producing waste products such as ethanol (like yeast do under anoxic conditions) or lactic acid (in bacteria and some muscle tissue when exercising strenuously). However, this process (fermentation) does not produce as much ATP.

In the presence of oxygen (or sulfur for our deep sea vent archaea), the final products of glycolysis (some three carbon molecule whose name I do not remember) are small enough to be transported into the probably the mitochondria's intermembrane space, where the Krebs Cycle occurs. The enzymes in the Krebs Cycle oxidize the sugar to reduce the electron carriers NAD+ and FADH+. (The oxidized sugars become CO2, which is shunted out of the cell and in humans, into the bloodstream toward the lungs etc.) Note that other macromolecules enter cellular respiration at the Krebs Cycle: fatty acid or amino acid chains hydrolyzed (in the liver probably) into similarly small transportable units (and the ammonia from breaking down proteins eventually exits through the urinary system).

On the inner mitochondrial membrane are proteins forming the electron transport chain (ETC) and our best friend, ATP synthase. Synthetase. Whatever. Biologists are not exactly known for their talent in naming things. When a reduced electron carrier binds to a protein in the ETC (is it also called an electron acceptor?), this induces a conformational change in that protein, catalyzing the oxidation of the electron acceptor. Oh god how the fuck does this go. Um. Uh.

[quick slate]

I think the oxidation releases electron(s), which bind to the protein. This induces another conformational change causing the protein to pump hydrogen ions (H+, protons, whatever)...I never remember which way. Into or out of the mitochondrial matrix. The electron(s) are then passed to the next protein in the ETC, which pumps more H+, until reaching the final electron acceptor: oxygen (or sulfur), forming water (or H2S) as a waste product.

The inner mitochondrial membrane is impermeable to H+. This is pretty important because a) this establishes a protein gradient and b) the only way for H+ to diffuse back across the mitochondrial membrane is by going through ATP synthase. The flow of H+ through ATP synthase causes its rotor domains (?) to spin, which moves this arm-looking domain (??) which brings phosphate and ADP together to produce ATP. So yeah, thanks to structural biologists, we know ATP synthase is literally a little motor powered by the proton gradient. Tada!

Depending on...I think which and how many electron acceptors are reduced in the Krebs Cycle, and where in the ETC they hand off their electrons, this affects the number of H+ pumped out and thus the number coming back in to power ATP synthase. That's why the total number of ATP produced by a single molecule of glucose is usually a range, like 32 to 36 or something?? Which is apparently about 30 or forty something percent—I certainly don't remember the numbers lol—efficient when compared to just lighting glucose on fire in a bomb calorimeter (I think??). That sounds pretty bad until you consider that manmade engines are about 10% efficient...and that fermentation produces usually fewer than half the number of ATP (I think?? lol). (It might be fewer than 30 for our deep sea vent archaea friends because O2, due to its electronegativity, is better final electron acceptor than sulfur. That's one reason so much speculative biology and SFF worldbuilding takes place on oxygenated worlds...

[random jay]

omg for once its smth i learned in my bio class

[quick slate]

(...even though Earth has 20% oxygen in the atmosphere probably mainly due to a giant oopsie by cyanobacteria. Archaea probably have their ETC on their cell membranes?)

That's the main part lol. This is a truly terrible explanation because it's a) way too long, b) way too jargony, and c) probably wrong. So to make it even longer...

(Even more) bonus tangents I thought about while writing this.

So I imagine engineers might not call the ETC a very robust system. One part breaking can cause the entire system to fail. The most famous of these is the poison cyanide, which causes the last enzyme in the ETC to fail. This stops the process cold, and then the poisoned person dies very quickly. I think experiments involving ETC poisons is how cell biologists figured out the order of the ETC. I think probably some previous research showed which poisons bind to which proteins, so if a poison still works after the application of a previous one, then the later poison's target is probably upstream of the earlier poison? I don't remember honestly.

There was also a molecule marketed as a weight loss drug that caused the mitochondrial membrane to be permeable to H+. This meant H+ could bypass the ATP synthase, so you can eat all you want and produce no ATP! But all that energy comes out as heat and killed people from overheating and starvation, probably.

I recently learned about bongkreic acid, a product produced by fermented corn products contaminated by a certain soil bacteria that produces the toxin as part of its fermentation process. I don't remember its exact mechanism, but it appears to also be a ETC poison with no antidote ): I'm so glad I watched that ChubbyEmu video during the day and not before bed lol.

Anyway, I'll let other people talk now.

[sonic blaze]

It's weird how delicate oxidative phosphorylation is, the only reason why it exists is because life had already changed earth to allow for heterotrophs to emerge. It is basically a statistical fluke that aerobic life developed this far, cuz a single compound could have easily killed every single aerobic organism, and even evolution would not have helped us.

If we ever foray into deep genetic editing, we should first fix this monstrous bit of code

[warped trout]

Oxidative phosphorylation is a crucial step in cellular respiration where cells generate ATP, the primary energy currency of the cell. This process occurs in the mitochondria and involves two main components: the electron transport chain (ETC) and ATP synthase.

Oxidative phosphorylation is a complex but highly efficient process where the ETC creates a proton gradient across the mitochondrial membrane, and ATP synthase utilizes this gradient to produce ATP. The chemiosmotic theory elegantly explains how this gradient drives ATP synthesis, highlighting the intricate interplay between the electron transport chain and ATP synthase in cellular energy production.

Oxidative phosphorylation is the primary method by which cells produce ATP, especially in aerobic organisms. This process is critical for energy-intensive cellular activities and maintaining cellular functions. The process is tightly regulated by cellular energy needs, oxygen availability, and other factors. Efficient energy production ensures cells can meet their metabolic demands while minimizing waste.

[floral vale]

Me a 14 year old thinking I can do one qotw 😭

[signal kelp]

my message wasn't delivered pls 😭

[signal kelp]

lol im 14 too but yk we could still try dw

anyways

[floral vale]

Broooo you got so much brainnn man!! Hats off I’m gonna go learn about this now

[signal kelp]

tysm! this was just a shot at answering the question but hope it's correct tho

[signal kelp]

Approximately 30-32 ATP molecules are generated from the ETC while the yield for glycolysis alone is only 2 ATP. ATP generation in oxydative phosphorylation is significantly greater than glycolysis alone due to the efficiency of energy extraction in the ETC.

Now we know that ETC generates proton gradients for oxydative phosphorylation, but i think i should include the significance of proton gradient in all this. So proton gradient produce most of the cell's ATP. During oxidative phosphorylation each pair of electrons donated by the NADH produced in mitochondria is believed to produce energy for the formation of about 2,5 molecules of ATP after substracting the energy needed for transporting the ATP to the cytosol.
For each pair of electrons transferred from NADH to O2, 4 protons are pumped by complex I, 4 by complex III and 2 by complex IV for a total of ten protons.

In the chemiosmotic theory of oxidative phosphorylation, electron transport via the respiratory chain to molecular oxygen creates a proton gradient across the inner mitochondrial membrane - which is normally impenetrable to protons - and proton are pumped outwards. This proton motive force can be used to "drive" the formation of ADP (adenosine diphosphate) to ATP (adenosine triphosphate) - which is thermodynamically unfavorable - reaction to the right via ATP synthase complex.

We can calculate the overall efficiency of the process, but i only have vague ideas of how to do that. However, I do recall that this process's efficiency is of approximately 40-45%, but that it is pretty high compared to other energy conversion processes.

so i know the explanation wasn't really clear, but i suck at explaining stuff and this was my best for this QOTW

others will come up with better stuff ((:

[strange marlin]

isnt phophorylation occuring soley for the purpose of atp synthesis when the atpase spins and creates ATP from the electrochemical gradient from the H+ ions created by the ETC?

[signal kelp]

I guess but I'm not rlly sure I follow, wdym exactly

[strange marlin]

well phosphorylation happens in two different processes, the light dependant reaction of photosynthesis, aswell as the ET Chemiosis part of cellular respiration. My answer was not directed at your previous comment but an attempt at trying to answer the question in a general sense i guess

[signal kelp]

Oh, sorry

[strange marlin]

not a problem at all no need to apologize

[solar parcel]

Off the top of my head, synthase for something not using ATP, synthetase for something that does. Of course, as biologists do, there are exceptions that make me mald

[signal kelp]

we still didn't get the answer?

[sharp violet]

@signal kelp , did you research the process, or have you copy pasted the text? In no way am I undermining your knowledge, I am just astounded by the detail of the answer

[signal kelp]

Nope, i researched the process myself basing myself on various sources which, well, took me quite some time if I'm being honest

[sharp violet]

Kudos, you will do great progress in life

[signal kelp]

Thanks!

[stone bramble]

Nope. Apologies, you'll get an example answer tomorrow

I'm currently neck deep in some experiments involving cellular spheroids and that took all my time and energy

[stone bramble]

You can remember the matrix as being in the middle or core of the mitochondrion. The mitochondrial matrix is thus the most inside part of a mitochondrion, so the protons are pumped FROM IT into the inter-membrane space. Nice answer

[stone bramble]

That compound is DNP (2,4-dinitrophenol) and it's extremely dangerous. It has a D50 dose that's smaller than even cyanide (which itself has ~2mg/kg body weight so about 140mg for a 70kg person (which is about 0.14 grams)).

[stone bramble]

Love this answer! Precise!

[stone bramble]

Nice work!!! 🤩🤩

ANSWER

Credit to @warped trout
|| Oxidative phosphorylation is a crucial step in cellular respiration where cells generate ATP, the primary energy currency of the cell. This process occurs in the mitochondria and involves two main components: the electron transport chain (ETC) and ATP synthase.

Oxidative phosphorylation is a complex but highly efficient process where the ETC creates a proton gradient across the mitochondrial membrane, and ATP synthase utilizes this gradient to produce ATP. The chemiosmotic theory elegantly explains how this gradient drives ATP synthesis, highlighting the intricate interplay between the electron transport chain and ATP synthase in cellular energy production.

Oxidative phosphorylation is the primary method by which cells produce ATP, especially in aerobic organisms. This process is critical for energy-intensive cellular activities and maintaining cellular functions. The process is tightly regulated by cellular energy needs, oxygen availability, and other factors. Efficient energy production ensures cells can meet their metabolic demands while minimizing waste. ||

Incredible and detailed answers were also provided by @quick slate and @signal kelp