Carbonic Anhydrase Question

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Dr Gerrard

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All right, so I thought I fully understood this, but EK is confusing me.

Where is this carbonic anhydrase? Is it in the plasma or the erythrocytes.

Does it catalyze both the forward reaction and the backwards reaction?

Is this the process?

CO2 is produced in tissues, diffuses into capillaries, where it is converted to bicarbonate by carbonic anhydrase. Next, bicarbonate enters the erythrocyte, where it remains until the blood reaches the lungs. When the blood reaches the lungs, the bicarbonate is then reconverted into CO2, which then leaves the red blood cells, diffuses out of the capillaries into the lung.

I think I am just confused as to where exactly the CO2-bicarbonate conversion happens and what catalyzes both the forward and the reverse reaction.

CO2 form tissues diffuses into capillaries, where most of it is eventually converted to bicarbonate by carbonic anhydrase

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Carbonic anhydrase is an enzyme. By definition, it must catalyze both the forward and reverse reactions.

I was pretty confused too the first time I came across it in EK. So basically at the tissues carbonic anhydrase converts carbon dioxide to HCO3- and H+. RBCs near the tissue pick it up, and it goes all the way to the lungs/alveoli, where again carbonic anhydrase converts HCO3- back to CO2 which is exhaled.

So I'm guessing that specific conditions favor the forward reaction at the tissues, and other conditions favor the reverse reaction at the lungs.
 
All right, so I thought I fully understood this, but EK is confusing me.

Where is this carbonic anhydrase? Is it in the plasma or the erythrocytes.

Does it catalyze both the forward reaction and the backwards reaction?

Is this the process?

CO2 is produced in tissues, diffuses into capillaries, where it is converted to bicarbonate by carbonic anhydrase. Next, bicarbonate enters the erythrocyte, where it remains until the blood reaches the lungs. When the blood reaches the lungs, the bicarbonate is then reconverted into CO2, which then leaves the red blood cells, diffuses out of the capillaries into the lung.

I think I am just confused as to where exactly the CO2-bicarbonate conversion happens and what catalyzes both the forward and the reverse reaction.

CO2 form tissues diffuses into capillaries, where most of it is eventually converted to bicarbonate by carbonic anhydrase

1. Carbonic anhydrase in inside RBCs.

2. Enzymes change reaction kinetics not thermodynamics, thus they don't preferentially favor forward VS reverse reactions. They lower the energy barrier thus increasing rates of BOTH forward and reverse reactions.

3. You have the overview of the process right, with minor issues. HCO3- is formed in the RBC, it does not enter the RBC.

The central point of the Carbonic acid/bicarbonate system is the facilitation of efficient exchange and transport of CO2. CO2 is very permeable to plasma membrane and HCO3- is NOT (for one it's charged). If this conversion didn't happen, RBCs will be the most inefficient CO2 transporters bcos CO2 will leak out all the time. Another benefit of this conversion is the maintenance of CO2 concentration gradient allowing passive diffusion from tissues to RBCs, otherwise equilibrium will be quickly reached and net flow of CO2 - from tissue to blood - ceases (process is analogous to glucose phosphorylation by most cells, to ensure intracellular glucose levels remain low)

AT tissues, CO2 diffuses into RBC, Carbonic anhydrase (CA) hydrates CO2 to HCO3- + H+ , HCO3- stays put inside da RBC and at the alveoli, CA dehydrates HCO3- to CO2 + H2O and u exhale..

Nice tidbits..
*At tissue courtesy of CO2 concentration, ph drops and shifts O2 dissociation curve rightwards causing O2 to dropoff at tissues (important for ETC).. Conversely at lungs, pH rises and O2 affinity to Haem increases, promoting oxygenation of haemoglobin.

*Bicarbonate loss at alveoli region causes CL- ion to exit RBC (CL- shift) to electrostatically balance charges..

*H2CO3 & HCO3 are conjugate pairs thus they buffer blood pH!!
 
Thanks guys, that really clears it up for me I think, (although JohnDoe and Bernoull are saying opposite things).

Anyways, so what about blood pH questions. If the entire process happens in the red blood cells, do the hydrogen ions produced from the reaction of CO2 leak out into the blood? I have seen a lot of questions about plasma pH, and am curious how this relates to all of that.

In all of these questions, you know that when blood pH decreases, in order to compensate, equilibrium of the reaction is shifted towards the CO2 side, and you get hyperventilation in order to get rid of this extra CO2. Correct?
 
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Those do help, but:

1) Once converted to bicarbonate, does this bicarbonate stay inside the cell or go back into the plasma?
2) What happens to the H+? Does this leave the cell or stay inside?
3) In cases of low blood pH, is more bicarbonate converted to CO2?
4) In cases of high blood pH, is more CO2 stored as bicarbonate rather than carboxyhemoglobin and in the blood?
 
Thanks guys, that really clears it up for me I think, (although JohnDoe and Bernoull are saying opposite things).

Actually, the broad strokes match up. Both assert that enzymes (as any catalysts) speed up both the forward and reverse reactions, which they do. That's the kinetics of the reaction. Then JohnDoe goes on to say:

So I'm guessing that specific conditions favor the forward reaction at the tissues, and other conditions favor the reverse reaction at the lungs.
And he's right. Here we're talking about thermodynamics. There's a buildup of CO2 at the tissues. By LeChatlier's principle, that moves the reaction in the forward direction to relieve the stress on the system and return it to equilibrium. "Shortage" of CO2 at the lungs drives the reaction backward.

Anyways, so what about blood pH questions. If the entire process happens in the red blood cells, do the hydrogen ions produced from the reaction of CO2 leak out into the blood? I have seen a lot of questions about plasma pH, and am curious how this relates to all of that.
I haven't found any of the AAMC practice tests or the real MCAT to care about the exact location of this enzyme. EK doesn't make it terribly clear because they don't think it matters. That company is all about focusing on what you'll probably need to know over trying to know everything. (I've found their approach quite helpful, but your mileage may vary.)

The most important things to understand about carbonic anhydrase (IMO) have been described above.

In all of these questions, you know that when blood pH decreases, in order to compensate, equilibrium of the reaction is shifted towards the CO2 side, and you get hyperventilation in order to get rid of this extra CO2. Correct?
You are focusing on the most important part for the MCAT here: 1) What causes the pH to drop (forward movement of the carbonic anhydrase-catalyzed reaction)?, 2) what does the body do about it?, and 3) what condition(s) will be created in the body as result of the compensatory action?

Probably stuff you don't need for the MCAT, but in case you care: Resp rate does generally increase in response to metabolic or respiratory acidosis, but hyperventilation is generally not a compensatory reaction. Hyperventilation actually often has CNS/endocrine causes (like release of stress hormones). Hyperventilation tends to upset homeostatic balance and results in respiratory alkylosis (because blowing off all available CO2 in the alveolar capillary beds drives pH up; the reaction shifts far to the left, but hyperventilation keeps getting rid of CO2 until bicarb in the locality is exhausted and buffering capacity is gone.). The body will try to compensate for respiratory alkylosis by slowing the breathing rate, but may not be able to overcome the underlying problem(s). There's a pretty good synopsis at http://emedicine.medscape.com/article/301680-overview.

Remember the broad strokes. EK is pretty good in their Bio materials at focusing in on the stuff that matters and glossing over what isn't important for the MCAT. If they don't cover it, (in my experience, anyway) you are unlikely to need it. There's plenty of low-hanging fruit to keep most people busy without stressing over the minutiae.
 
Those do help, but:

1) Once converted to bicarbonate, does this bicarbonate stay inside the cell or go back into the plasma?
2) What happens to the H+? Does this leave the cell or stay inside?
3) In cases of low blood pH, is more bicarbonate converted to CO2?
4) In cases of high blood pH, is more CO2 stored as bicarbonate rather than carboxyhemoglobin and in the blood?

#1 & 2: I'd encourage you not to worry about the inside/outside the cell sort of thing. The MCAT seems to care about blood pH, not RBC pH.

#3: Remember what low pH means... higher concentration of H+. Higher H+ concentrations raise the reaction quotient (Q) for the reaction and stress the system. According to LeChatlier's principle the reaction will be driven backward (using up bicarb and making CO2) to achieve equilibrium again. Note that the presence of carbonic anhydrase doesn't change this. The equilibrium quotient is the same regardless. The enzyme just makes getting there (from either direction) much, much faster.

#4: Again, I think this is too finicky a question for the MCAT. It's important to know that bicarb exists in both forms. The percentages will differ considerably throughout the body (based on its own dissociation curve), but remember that the amount that can be stored as carboxyhemoglobin is limited by valence of the hemoglobin, and amount dissolved in the blood is limited by its solubility (which is pretty great for pretty much all small, charged species). I think it's more important to understand the concepts behind the behavior, though.
 
1. Carbonic anhydrase in inside RBCs.

2. Enzymes change reaction kinetics not thermodynamics, thus they don't preferentially favor forward VS reverse reactions. They lower the energy barrier thus increasing rates of BOTH forward and reverse reactions.

3. You have the overview of the process right, with minor issues. HCO3- is formed in the RBC, it does not enter the RBC.

The central point of the Carbonic acid/bicarbonate system is the facilitation of efficient exchange and transport of CO2. CO2 is very permeable to plasma membrane and HCO3- is NOT (for one it's charged). If this conversion didn't happen, RBCs will be the most inefficient CO2 transporters bcos CO2 will leak out all the time. Another benefit of this conversion is the maintenance of CO2 concentration gradient allowing passive diffusion from tissues to RBCs, otherwise equilibrium will be quickly reached and net flow of CO2 - from tissue to blood - ceases (process is analogous to glucose phosphorylation by most cells, to ensure intracellular glucose levels remain low)

AT tissues, CO2 diffuses into RBC, Carbonic anhydrase (CA) hydrates CO2 to HCO3- + H+ , HCO3- stays put inside da RBC and at the alveoli, CA dehydrates HCO3- to CO2 + H2O and u exhale..

Nice tidbits..
*At tissue courtesy of CO2 concentration, ph drops and shifts O2 dissociation curve rightwards causing O2 to dropoff at tissues (important for ETC).. Conversely at lungs, pH rises and O2 affinity to Haem increases, promoting oxygenation of haemoglobin.

*Bicarbonate loss at alveoli region causes CL- ion to exit RBC (CL- shift) to electrostatically balance charges..

*H2CO3 & HCO3 are conjugate pairs thus they buffer blood pH!!


Hey Bernoull,

Had a question about your kick ass explanation. I bolded part it above. I thought HCO3- would go into the plasma and not stay put, and thats why at the alveoli it diffuses back into the RBC.

Btw, where is H+ the whole time? Stuck to Hb? then that would mean it has no effect on pH ya?

anyway hope everything is kickin on your end, peace

steve
 
Hey Guys,

I was confused on the fact that when bicarb ion leaves the RBC like it says in EK causing the Cl- ion to come back in then where exactly does it go? From the diagram it appears as if it goes to the plasma to pick up CO2? Like basically im confused on where does it go to pick up CO2?
Thanks!
 
CO2 is very permeable to plasma membrane and HCO3- is NOT (for one it's charged).

You mean CO2 can diffuse across the plasma membrane because CO2 is non-polar, like the lipid bilayer mostly is, while the hydrogen carbonate ion is somewhat polar (it is trigonal planar around the central carbon) but it is not perfectly symmetrical.
 
Hey Guys,

I was confused on the fact that when bicarb ion leaves the RBC like it says in EK causing the Cl- ion to come back in then where exactly does it go? From the diagram it appears as if it goes to the plasma to pick up CO2? Like basically im confused on where does it go to pick up CO2?
Thanks!

It doesn't pick up CO2. CO2 becomes Bicarb.
Picture30.jpg


You mean CO2 can diffuse across the plasma membrane because CO2 is non-polar, like the lipid bilayer mostly is, while the hydrogen carbonate ion is somewhat polar (it is trigonal planar around the central carbon) but it is not perfectly symmetrical.

That's exactly what permeable means.
 
It doesn't pick up CO2. CO2 becomes Bicarb.
Picture30.jpg


Hey ,
So on the way in CO2 becomes bicarb and on the way out bicarb becomes CO2? So depending on what our body needs is which determines which way it goes?

Thanks!


That's exactly what permeable means.
 
Thanks, but how do we know which way it will go
I answered this in your previous post about this topic. I don't know if you cared to read it, but here it is again, lol:

Bicarbonate is an important component of blood plasma (acts to buffer the blood and maintain a pH of 7.4). As you probably know, a byproduct of metabolism is CO2 expulsion. RBC's travelling to these tissues expel free oxygen (bound to hemoglobin), and at the same time, CO2, a nonpolar molecule, diffuses through the RBC and is eventually bound to carbonic anhydrase, an enzyme in RBC's. Like all enzymes and catalysts, it helps to achieve a steady equilibrium more quickly. In this case, we have CO2 + H2O (forming a very brief intermediate: H2CO3, which decomposes to): HCO3- and H+. Some of this H+ binds to hemoglobin (shifts to low affinity Hb) and helps facilitate the release of more oxygen into metabolically active tissues, down its partial pressure gradient (Bohr effect).

The equilibrium can also be disrupted by other conditions as well. In the lungs, we exhale CO2 and therefore the capillaries at the lungs have a very low amount of CO2. At the same time though, binding oxygen (shifts to high affinity Hb) will cause bound H+ to be released. This will shift to produce more CO2, which is released into the air.

So in summary, it facilitates the release of waste products (CO2),facilitates entry of essential nutrients (O2), and helps to buffer the blood at a constant pH (HCO3-).
 
Thanks, but how do we know which way it will go

Systemically you can assume it's CO2 -> Bicarb.

In pulmonary capillaries you can assume it's Bicarb -> CO2.

I answered this in your previous post about this topic. I don't know if you cared to read it, but here it is again, lol:

Bicarbonate is an important component of blood plasma (acts to buffer the blood and maintain a pH of 7.4). As you probably know, a byproduct of metabolism is CO2 expulsion. RBC's travelling to these tissues expel free oxygen (bound to hemoglobin), and at the same time, CO2, a nonpolar molecule, diffuses through the RBC and is eventually bound to carbonic anhydrase, an enzyme in RBC's. Like all enzymes and catalysts, it helps to achieve a steady equilibrium more quickly. In this case, we have CO2 + H2O (forming a very brief intermediate: H2CO3, which decomposes to): HCO3- and H+. Some of this H+ binds to hemoglobin (shifts to low affinity Hb) and helps facilitate the release of more oxygen into metabolically active tissues, down its partial pressure gradient (Bohr effect).

The equilibrium can also be disrupted by other conditions as well. In the lungs, we exhale CO2 and therefore the capillaries at the lungs have a very low amount of CO2. At the same time though, binding oxygen (shifts to high affinity Hb) will cause bound H+ to be released. This will shift to produce more CO2, which is released into the air.

So in summary, it facilitates the release of waste products (CO2),facilitates entry of essential nutrients (O2), and helps to buffer the blood at a constant pH (HCO3-).

Lots of good information, but this does not answer the question of which way the reaction is going to go.
 
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