Electron Transport Chain Inhibition

[pdiddy348]

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Can someone please explain the consequences of uncouplers (2,4-DNP) and ATPase blockers and how it effects the overall cellular respiration? Basically, can you guys trace the outcome all the way back to glycolysis, I'm a bit confused. I hope this thread made sense.

 

[dsh]

2,4-DNP will uncouple some part of the whole cytochrome electron exchange thingamabob and keep you from generating all the atp you should get. As a result, your metabolism goes up to make more atp. I think that's all you really need to know about it, I'm not sure how the ATPase one's work but it's probably similar.

In the Twenties they used it in cocktails because it gave you a nice buzz and made you feel warm. What they didn't know was that it caused blindness and other fun stuff. If you ever read The Great Gatsby, 2,4-DNP was what the "elixir" was.

 

[DrChandy]

Can someone please explain the consequences of uncouplers (2,4-DNP) and ATPase blockers and how it effects the overall cellular respiration? Basically, can you guys trace the outcome all the way back to glycolysis, I'm a bit confused. I hope this thread made sense.

ATPases are present in the citric acid cycle. The presence of ATPases in the cycle allow for the ultimate production of NADH, FADH2, and ATP. Block one of the ATPases, and you compromise the cycle. For the MCAT, just know the net products from glycolysis and the citric acid cycle, reasons for why and where ATP is used in the above processes, the components of the electron transport chain (ETC), and the yield of ATP per molecule of NADH or FADH2 per run in the ETC.

 

[Mister Pie]

2,4-DNP will uncouple some part of the whole cytochrome electron exchange thingamabob and keep you from generating all the atp you should get. As a result, your metabolism goes up to make more atp. I think that's all you really need to know about it, I'm not sure how the ATPase one's work but it's probably similar.

In the Twenties they used it in cocktails because it gave you a nice buzz and made you feel warm. What they didn't know was that it caused blindness and other fun stuff. If you ever read The Great Gatsby, 2,4-DNP was what the "elixir" was.

That is an awesome factoid. Too bad only other nerds will appreciate it.

 

[grapeflavorsoda]

Can someone please explain the consequences of uncouplers (2,4-DNP) and ATPase blockers and how it effects the overall cellular respiration? Basically, can you guys trace the outcome all the way back to glycolysis, I'm a bit confused. I hope this thread made sense.

the atpase blocker and uncouplers have different effects on the metabolic pathway.

Uncouplers like 2,4-dintrophenol dissipates the proton gradient by acting as a shuttle(similar to phase-transfer agents like quaternary ammonium salt) by possessing capacity to act as both hydrophilic(deprotonated form) and hydrophobic form(protonated form). Since ATP-synthetase(aka F-class pump or simply F-pump) couples the electrochemical gradient to chemical bond through the mechanical means, dissipating proton gradient will simply reduce the ATP production rate without affecting the preceding metabolic pathways(glycolysis and Kreb cycle).

However, the inhibitor of ATP-synthetase will affect the electron-transport chain and consequently affects glycolysis and kreb cycle. The major reason for this difference is that inhibitor will not allow the dissipation of proton gradient whereas the uncoupler will. If the F-pump is not allowed to dissipate the proton gradient, potential difference will build up across the inner membrane such that it will exceed the maximum work limit that can be generated from the sequential potential drop of electron via ETC(recall that mito lacks V-class pump that can symport chloride anion with proton?). This situation is analgous to the galvanic cell with missing salt bridge; even though there is enough reduction potential for the cell to generate the current, it will stop after few seconds of generation current because of the charge build-up(which is ultimately the source of counter potential that is equal to the cell potential thus ultimately making the system potentia = 0 volt).
As a result of this proton gradient build up caused by the F-class pump inhibitor, the ETC won't be able to transport electrons thus causing the build up of reductants generated in the glycolysis and kreb cycle. So the whole system of this particular metabolic pathway will be shut down and the organism will try to divert the accumulation of reductants(NADH and FADH2) by reducing the pyruvate and inhibiting the Kreb cycle altogehter.


in short, uncoupler will not inhibit glycolysis nor kreb cycle but reduces the efficiency of ATP synthetase, whereas the ATP-synthetase inhibitor will block the kreb-cycle(but not glycolysis) causing similar cellular phenomena seen under anaerobic conditions.

 

[NilamPatel]

That is an awesome factoid. Too bad only other nerds will appreciate it.

nerds are people too

somebody give grapesoda a cookie, that was an awesome explanantion!!!

 

[priyanka]

ATPases are present in the citric acid cycle. The presence of ATPases in the cycle allow for the ultimate production of NADH, FADH2, and ATP. Block one of the ATPases, and you compromise the cycle. For the MCAT, just know the net products from glycolysis and the citric acid cycle, reasons for why and where ATP is used in the above processes, the components of the electron transport chain (ETC), and the yield of ATP per molecule of NADH or FADH2 per run in the ETC.

lol, I like your avatar. The OH stereochemistry on your glucose molecule is not right though😛

 

[gotgame83]

2,4-DNP will uncouple some part of the whole cytochrome electron exchange thingamabob and keep you from generating all the atp you should get. As a result, your metabolism goes up to make more atp. I think that's all you really need to know about it, I'm not sure how the ATPase one's work but it's probably similar.

In the Twenties they used it in cocktails because it gave you a nice buzz and made you feel warm. What they didn't know was that it caused blindness and other fun stuff. If you ever read The Great Gatsby, 2,4-DNP was what the "elixir" was.

Yes I believe there were a few studies showing that when used excessivly it could promote cateracts, and then a few studies showing it did nothing of the sort. I didnt know it was used in drinks though. Im pretty sure it was an active in dynamite and when handled the yellow powder was absorbed through the skin(it stains your still pretty good too) The workers were getting over heated hower they did lose lots of fat. It was at this time in the 20's that I believe it was sold as a fat loss agent however there were few people who claimed it messed with their vision. Recently it did make a come back in the 90's were people would use 200-600mg day for a few weeks for rapid fat loss. Just becareful its not the crystal form because that is EXTREMELY potent and can cause exsessive heat increases. It also can have some ummm "colorful" side effects if your a male.