how does 2,3 BPG leave the cells to affect hemoglobin binding curve?

[Astra]

I understand how CO2 leaves the cell due to the fact that the molecule is nonpolar.

However, 2,3 BPG is polar

( https://upload.wikimedia.org/wikipe...ate.svg/220px-2,3-Bisphosphoglycerate.svg.png)

, so what mechanism allows it to transverse the hydrophobic cell membrane?

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[theonlytycrane]

you already know the answer based on your understanding of what can and can't cross the membrane 🙂 It has to be transported out- this may be either directly or indirectly as a different molecule and converted back to 2,3-BPG somewhere else.

 

[aldol16]

I understand how CO2 leaves the cell due to the fact that the molecule is nonpolar.

However, 2,3 BPG is polar

( https://upload.wikimedia.org/wikipe...ate.svg/220px-2,3-Bisphosphoglycerate.svg.png)

, so what mechanism allows it to transverse the hydrophobic cell membrane?

you already know the answer based on your understanding of what can and can't cross the membrane 🙂 It has to be transported out- this may be either directly or indirectly as a different molecule and converted back to 2,3-BPG somewhere else.

It doesn't need to leave the cell. The idea is that it doesn't leave the cell. You know that 2,3-BPG modulates the effects of hemoglobin. Hemoglobin is a protein found in red blood cells, or erythrocytes. It would be a big hassle to make 2,3-BPG somewhere else, get it into the bloodstream, and then transport it into the red blood cells. So instead, the body does something much simpler - it makes the protein in the red blood cells. So it's only expressed in RBCs and acts locally - it doesn't need to be transported!

 

[Astra]

It doesn't need to leave the cell. The idea is that it doesn't leave the cell. You know that 2,3-BPG modulates the effects of hemoglobin. Hemoglobin is a protein found in red blood cells, or erythrocytes. It would be a big hassle to make 2,3-BPG somewhere else, get it into the bloodstream, and then transport it into the red blood cells. So instead, the body does something much simpler - it makes the protein in the red blood cells. So it's only expressed in RBCs and acts locally - it doesn't need to be transported!

So make sure I have this right, This is my understanding.

2,3 BPG is a byproduct of glycolysis.

This byproduct is present in tissues of the body and as well as red blood cells.

When cellular respiration increases, 2,3 BPG levels increase in the tissue AND red blood cells.

This increase in 2,3 BPG in RBC causes a decreased affinity for O2.

This causes a right shift in the binding curve, leading to more O2 reaching the tissues.

 

[aldol16]

So make sure I have this right, This is my understanding.

2,3 BPG is a byproduct of glycolysis.

This byproduct is present in tissues of the body and as well as red blood cells.

When cellular respiration increases, 2,3 BPG levels increase in the tissue AND red blood cells.

This increase in 2,3 BPG in RBC causes a decreased affinity for O2.

This causes a right shift in the binding curve, leading to more O2 reaching the tissues.

2,3-BPG is not a byproduct of glycolysis! 2,3-BPG is produced by bisphosphoglycerate mutase, which transforms 1,3-BPG, which is a glycolytic intermediate, into 2,3-BPG. 2,3-BPG is not produced in glycolysis normally. I repeat: 2,3-BPG is not produced in glycolysis normally. Producing 2,3-BPG during glycolysis would squander the one of the intermediates that could be used for substrate-level phosphorylation for no apparent physiological reason.

That's why 2,3-BPG is only produced in erythrocytes and placental cells - only those cells express bisphosphoglycerate mutase, which is required to produce 2,3-BPG.

 

[Astra]

2,3-BPG is not a byproduct of glycolysis! 2,3-BPG is produced by bisphosphoglycerate mutase, which transforms 1,3-BPG, which is a glycolytic intermediate, into 2,3-BPG. 2,3-BPG is not produced in glycolysis normally. I repeat: 2,3-BPG is not produced in glycolysis normally. Producing 2,3-BPG during glycolysis would squander the one of the intermediates that could be used for substrate-level phosphorylation for no apparent physiological reason.

That's why 2,3-BPG is only produced in erythrocytes and placental cells - only those cells express bisphosphoglycerate mutase, which is required to produce 2,3-BPG.

Derp. My bad.

So my question is this then. What affects the red blood cells' rate of conversion of 1,3 BPG into 2,3 BPG?

Exercising increases glycolysis in cells, so does it also increase it in red blood cells or just tissues?

 

[aldol16]

So my question is this then. What affects the red blood cells' rate of conversion of 1,3 BPG into 2,3 BPG?

Well, this is basically an enzyme kinetics question in disguise. You're asking what affects the rate of conversion. So why don't you answer that, given that the same variables that are relevant in Michaelis-Menten kinetics are relevant here?

Exercising increases glycolysis in cells, so does it also increase it in red blood cells or just tissues?

Great question. Glycolysis is increased in cells whenever those particular cells undergo a burst of activity. So for instance, glycolysis increases in muscle cells with activity and in the fight-or-flight response. In contrast, glycolysis goes down in the liver during fight-or-flight or when fasting due to the high Km of GLUT2 so that the liver doesn't compete with the muscles for fight-or-flight or when glucose is lacking. So the answer to your question is it depends on what tissue you're talking about. Your RBCs are always undergoing glycolysis because they don't have mitochondria. Exercising would likely increase glycolysis in RBCs as well because those cells will want to make more hemoglobin and making macromolecules costs a lot of energy - and glycolysis is the only source of energy for RBCs.

 

[Astra]

Well, this is basically an enzyme kinetics question in disguise. You're asking what affects the rate of conversion. So why don't you answer that, given that the same variables that are relevant in Michaelis-Menten kinetics are relevant here?



Great question. Glycolysis is increased in cells whenever those particular cells undergo a burst of activity. So for instance, glycolysis increases in muscle cells with activity and in the fight-or-flight response. In contrast, glycolysis goes down in the liver during fight-or-flight or when fasting due to the high Km of GLUT2 so that the liver doesn't compete with the muscles for fight-or-flight or when glucose is lacking. So the answer to your question is it depends on what tissue you're talking about. Your RBCs are always undergoing glycolysis because they don't have mitochondria. Exercising would likely increase glycolysis in RBCs as well because those cells will want to make more hemoglobin and making macromolecules costs a lot of energy - and glycolysis is the only source of energy for RBCs.

I finally have the complete picture!

You exercise.

This causes an increase in glycolysis in RBC.

This increases the amount of 1,3 BPG created.

This increases the substrate concentration for bisphosphoglycerate mutase.

This leads to increased 2,3 BPG.

This increase in 2,3 BPG in RBC causes a decreased affinity for O2.

This causes a right shift in the binding curve, leading to more O2 reaching the tissues.

 

[theonlytycrane]

thanks for the correction @aldol16! And awesome question @Astra118. Bookmarking as well 🙂

 

[popopopop]

I finally have the complete picture!

You exercise.

This causes an increase in glycolysis in RBC.

This increases the amount of 1,3 BPG created.

This increases the substrate concentration for bisphosphoglycerate mutase.

This leads to increased 2,3 BPG.

This increase in 2,3 BPG in RBC causes a decreased affinity for O2.

This causes a right shift in the binding curve, leading to more O2 reaching the tissues.

Exercising upregulates GLUT4 recruitment to the cell membrane of muscle+adipose tissues, so more glycolysis for sure. GLUT1 is also on heart and skeletal tissues, but it won't be upregulated like GLUT4 would. In short, exercising would definitely be raising glycolysis levels.