Why FADH2 but Not NADH in Brain and Skeletal Muscle Cells?

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Discussion Overview

The discussion centers around the differences in how NADH and FADH2 are utilized in brain and skeletal muscle cells, particularly regarding their transport into mitochondria and the implications for ATP yield. It explores biochemical pathways, specifically glycolysis and oxidative phosphorylation, and the mechanisms involved in electron transport.

Discussion Character

  • Technical explanation
  • Conceptual clarification
  • Debate/contested

Main Points Raised

  • One participant notes that NADH + H+ cannot enter the mitochondria of brain and skeletal muscle cells, while FADH2 can, but does not explain why this is the case.
  • Another participant explains that NADH + H+ produced during glycolysis must be transported into the mitochondria via shuttles, specifically mentioning the glycerophosphate and malate-aspartate shuttles.
  • It is clarified that NADH and FADH2 produced in the Krebs cycle do not face the same transport issues since this cycle occurs in the mitochondrial matrix.
  • A participant questions whether the entire NADH + H+ molecule enters the mitochondria or just its components, leading to a response that only electrons enter the mitochondria.
  • Another participant raises a question about why electrons prefer FAD as a carrier instead of NAD+ within the mitochondria.
  • It is mentioned that the malate-aspartate shuttle transfers electrons from cytosolic NADH to mitochondrial NAD+, while the glycerophosphate shuttle transfers electrons to mitochondrial FAD, with a note of uncertainty regarding the evolutionary preference of these shuttles.
  • One participant requests additional reading material to support the claim about the glycerophosphate shuttle's use in the brain.
  • Another participant expresses uncertainty about whether one shuttle mechanism is preferred over the other in the brain.

Areas of Agreement / Disagreement

Participants express uncertainty regarding the mechanisms and preferences of electron transport shuttles in brain cells, indicating that multiple competing views remain without a clear consensus on the preferred shuttle in the brain.

Contextual Notes

There are limitations in understanding the efficiency and evolutionary reasons behind the use of different shuttles, as well as the specifics of how NADH + H+ is utilized in mitochondria.

crays
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Hi, my book says that in the brain and skeletal muscle cells, it only yields a total of 36 ATP because NADH + H+ cannot enters the brain and skeletal muscle cells' mitochondria. But why FADH2 can is not stated. Can someone tell me why?

Also, since NADH + H+ is formed inside the mitochondria why would NADH + H+ cannot be used in the brain? They are still formed inside the mitochondria right?

Also, i would like to ask if my understanding is correct. NADH + H+'s H+ is used to push hydrogen against the concentration so that it will go through a gradient and ATP is synthesized from the ATP synthetase. Is this right?

Lots of question, thanks for the help.
 
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Two NADH + H+ are produced during glycolysis, which occurs in the cytoplasm of cells. For the cell to use these molecules in oxidative phosphorylation (which occurs inside the mitochondria), the cell must have some way of transporting the "energy" stored by these cytoplasmic NADH + H+ into the mitochondria. There are two means by which this can occur, the glycerophosphate shuttle and the malate-aspartate shuttle.

The NADH and FADH2 molecules that are produced during the Krebs cycle do not have these problems as the Krebs cycle occurs in the mitochondrial matrix.

Yes, the energy from the NADH is used to push hydrogen against its concentration gradient. Proton gradient provides the energy for the ATP synthase enzyme to generate ATP.
 
Thanks Ygggdrasil. one more question, in the glycolysis process. Does the WHOLE NADH + H+ enters the mitochondrian or just the electrons? or just the H+? Because they can only be changed to ATP in the mitochondria right?
 
if its the electrons, why does the electrons choose FAD as it's carrier inside the mitochondria but not NAD+
 
When the cell uses the malate-aspartate shuttle, the electrons from cytosolic NADH are transferred to mitochondrial NAD+. However, when the cell uses the glycerophosphate shuttle, the electrons from cytosolic NADH are transferred to mitochondrial FAD.

I'm not completely sure why cells have evolved and maintained the glycerophosphate shuttle as it is less energy efficient than the malate-aspartate shuttle. Perhaps the relevant issue is speed and the cell requires the combination of the two shuttles in order to transport the electrons from NADH quickly enough to meet demand (regeneration of NAD+ in the cytosol is important for glycolysis to continue).
 
Thanks ygggdrasil, but do you have reading material like from wiki or anything to backup your statement that in the brain it uses the glycerophosphate shuttle? thanks~
 
I don't know whether one mechanism is preferred or not in the brain.
 

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