Thursday, 6 August 2020

Electron Transport Chain (ETC) and ETC Inhibitors

Electron Transport Chain (ETC)

The goal of the electron transport chain is to couple energy stored in electron acceptors to a proton gradient that derives ATP synthesis. ETC is takes place in inner mitochondrial membrane.
In inner mitochondrial membrane has a series of complexes. 

  There are five complex proteins, which helps in ATP synthesis. Additionally the presence of two other molecules that act not as complex but they are embedded in this area of the electron transport chain. Those are Coenzyme-Q and Cytochrome-C, now technically these are broken into two distinct parts of oxidative phosphorylation.  

  The complex portion from 1 to 4 including coenzyme-Q and cytochrome-C is known as the electron transport chain, because this is where electrons get shuffled from one complex to the other. The ATP synthase which pumps the proton gradient to generation ATP is technically known as chemiosmosis. The combination of the electron transport chain plus chemiosmosis that is togather known as oxidative phosphorylation.


How ETC works ?

 Protons that are present in the mitochondrial metrix. TCA cycle goal is to produce NADH and FADH2 for use in the electron transport chain. so along comes NADH and NADH2 approaches complex-1, NADH can give up it's proton and give up it's electrons and become NAD+. 

  In the process it donates it's electron to complex-1. When the electron enter complex-1 complex-1 becomes supercharged. It has the energy to pump the proton from the mitochondrial matrix into the inter membrane space as it does this it pumps more and more protons from the mitochondrial matrix into inter membrane space and you get the accumulation of protons on the other site of the membrane. This pumping is only made possible by the electron given up from NADH and supercharge complex-1.

   After while the electron will sit in complex-1 and the proton gradient is beginning to from on the top in the inter membrane space you have much more protons than exists. 

 Now at this point the gradient is being to form and complex will pass it's electrons to Coenzyme-Q. The electrons will go to Co-Q and sit there awaiting further instruction. 

 Now at this point FADH2 comes along and approaches complex -2 Just like NADH, FADH2 was produced in the TCA cycle. it migrates here in ETC and begins it's electrons and turn into FAD in this process it donates it's electron to complex-2.
  Complex -2 however can not become supercharged and can not pump protons from the mitochondrial metrix into the inter membrane space. 

 So the electron sits in complex-2 and awaits further instruction and ultimately gets passed to Co-Q. NADH only works at complex-1, FADH2 only works at complex-2
So the electrons given up from NADH go from one to Co-Q and the electrons given up by FADH2, from complex-2 to Co-Q.

Now it's important to understand something that's very high yield Co-Q is common electron acceptor from both complex-1 and complex-2. It's also incredibly important and very high yield to remember that NADH only gives up it's electrons at complex-1 and FADH2 only gives up it's electrons at complex-2 at this point the electrons are sitting in Co-Q and they are passed to complex-3. 

 It's supercharges complex-3 which creates enough energy potential to pump the proton from the mitochondrial Matrix through complex-3 into the inter membrane space. Complex-3 is being super charged by the shuffling of electrons both from complex-1 and complex-2 to    Co-Q to complex-3 supercharging it and helping to created this proton gradient in the inter membrane space. 

  You are getting the accumulation of protons there's a much greater positive charge on the inter membrane space. than there is in the mitochondrial Matrix so we are containing to form a very big proton gradient at this point complex-3 will pass it's electrons on to cytochrome-C
 
  The electrons arrive and then get post to complex-4. At complex-4 the electron enter it and supercharge. It just like we have seen in charged complex-3 and in complex-1,once supercharged complex-4 has enough energy to pump protons from the mitochondrial Matrix into the inter membrane space. 

  Again the proton gradient continues to form the inter membrane space is laced with tons of positively charged protons. So there's a proton gradient compared to the mitochondrial matrix which has fewer protons at this point complex-4.

Electrons sitting inside of it and it needs to pass to the final electron acceptor the final electron acceptors is oxygen. The electrons are passed to oxygen. 
  The electrons are passed to oxygen. Which splits into two oxygen ions and protons are added creating two water molecul. Now at this point we have formed a massive proton gradient there are so many protons in the inter membrane space and so fewer protons in the mitochondrial Matrix. 
Now at this point that ATP synthase comes into play. ATP synthase is going to make use of this proton gradient to generate massive amounts of ATP. So along comes the molecule ATP and ADP. Wants to turn into ATP which is a higher energy throughout the body but in order to catalyze the conversion. 

  We have to put energy source into this reaction because you can't just go from a lower energy source ADP to a higher energy molecule ATP. Without some type of energy input it's at this point that ATP synthase takes advantage of the proton gradient which was being formed by complexes 1,3 & 4. 

 The protons will always want to flow down it's gradient that is to say molecules in general like to flow from high energy states to low energy states to achieve equilibrium.  
  Protons will flow from the inter membrane space down through ATP synthase Bach to the mitochondrial matrix and when they do this it is an energy input that catalyses the conversion of ADP to ATP. That is how the energy is formed and massive amounts of ATP are formed during that step because there's such a large proton gradient that can continuously flow down to hill.

Now as those protons come across ATP synthase they build back up on the mitochondrial matrix. So they are sitting in front of complexes 1,3 & 4 ready to be pumped back up into the inter membrane space. 

   When complex 1,3 & 4 gets super charged as you can see the cycle continuous and the electron transport chain can continue to turn out ATP, so long as NADH2  and FADH2 are being shuffled from the TCA cycle to the electron transport chain to continue the flow of protons.

Inhibitors Electron Transport Chain
• Rotenone inhibits complex-1 
• Antimycin inhibits complex-3
• Cyanide and carbon monoxide 
   inhibits complex-4 and 
  cytochrome-C
• Oligomycin inhibits ATP 
  synthase and uncoupling 
  agent  
  such as 2 for DNP,uncouples 
  the proton gradient and  
  inhibits  
  the proton gradients ability to      pump 
  protons down through ATP 
  synthase.

these are five electron transport chain inhibitors.



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