This forum made possible through the generous support of SDN members, donors, and sponsors. Thank you.

BeerHelpsMeStudy

Full Member
7+ Year Member
Joined
Jul 9, 2015
Messages
101
Reaction score
134
Considering the bicarbonate buffering system in the blood, if the enzyme carbonic anhydrase's activity is inhibited, wouldn't this lead to an increased concentration of CO2 AND H2O at the tissue level? I'm reviewing the AAMC Sample Exam and I selected that CO2 concentrations would increase (correct answer), but now that I'm thinking about it... wouldn't H2O concentrations increase (also an answer choice, albeit incorrect) as well?

Many thanks

Edit- For reference: question 48 on AAMC 2015 MCAT Sample Exam

Members don't see this ad.
 
Well, remember that water is the biological solvent so the activity of a single enzyme would likely be unable to change the concentration of water significantly - it's 55 M under standard biochemical conditions. So yeah, while the enzyme's inhibition would cause "buildup" of substrates, it likely wouldn't affect water concentration substantially. To illustrate, the physiological concentration of bicarb is 10-50 mM. So even if all of the bicarb on the body, even using the more liberal estimate, were turned into water (highly unlikely to begin with), the concentration of water would only go to 55.05 M.

Furthermore, water is constantly being recycled throughout your body and you can imagine how critical it is to keep the water level well-regulated. So even if the water balance were perturbed significantly by inhibition of this enzyme (highly unlikely to begin with), the balance would be quickly restored so your cells don't become hypotonic
 
  • Like
Reactions: 1 user
Good answer @aldol16.

You can also look at the question from a different angle, that I feel is more inline with MCAT reasoning.

Recall the entire bicarbonate buffering system in the blood, with CO2 on one end and O2 on the other.

It should look something like this (in the tissues, it's running the other way in the lungs):

ofZkobj.png

The keyword in the question is tissue. When the MCAT talks about the bicarbonate buffering system in the tissue, it's saying that O2 is being used by cells, and CO2 is being released by them. When it talks about it in the lungs, it's saying O2 is entering the bloodstream and CO2 is exiting it.

When the system is functioning normally, carbonic anhydrase functions to help maintain constant levels of CO2 and O2 in the blood by converting CO2 to HCO3, and vice versa.

If you look at the diagram, you can see that if carbonic anhydrase is inhibited and CO2 is increasing, then CO2 will build up in the tissues and plasma. H2O concentration won't be affected, however. (If anything, it might actually decrease, because the reaction is still proceeding in the forward direction and thus being used up. This is only if you consider it as a reactant whose concentration can actually meaningfully change instead of as the biological solvent.)

Hope this helps.
 
Last edited:
If you look at the diagram, you can see that if carbonic anhydrase is inhibited and CO2 is increasing, then CO2 will build up in the tissues and plasma. H2O concentration won't be affected, however. (If anything, it might actually decrease, because the reaction is still proceeding in the forward direction and thus being used up. This is only if you consider it as a reactant whose concentration can actually meaningfully change instead of as the biological solvent.)

I'm sorry, now I'm looking at your diagram and I'm confused. What are the "out" and "in" relative to? I didn't understand the argument you were trying to present in the quoted segment above. So if CO2 isn't being used up in the cell and instead is being exported into the tissue. Now, which reaction is still proceeding in the forward direction? The reaction consuming water is being inhibited here so it's not proceeding in the forward direction. Is there another reaction using water?
 
Members don't see this ad :)
First off, thanks for asking for the clarification. I wasn't sure if my diagram or explanation would be that clear or not, and evidently they aren't. (For an excellent version of the diagram, check the ExamKrackers texbook).

The 'in' refers to inside a red blood cell, while the 'out' refers to outside a red blood cell, which can be plasma, extracellular space, cells, tissues, lungs, etc.

To clarify my reasoning, look specifically at this part of the diagram:

CO2 + H2O -CA-> HCO3- + H+

In the tissues, CO2 is released into the bloodstream, causing this reaction to proceed to the right. (This is reversed in the lungs).

Recall that catalysts, and thus enzymes, only speed up the rate of a reaction, but don't affect the final equilibrium concentrations of products and reactants. In other words, an enzyme just brings a reaction to its equilibrium concentrations (much) faster than if there were no enzyme.
However, even if the the enzyme is inhibited, or not even present, the system will still move towards equilibrium concentrations.

In the case of the bicarbonate buffering system in the tissues, CO2 is being released into the tissues. Under normal conditions, the CO2 is very rapidly converted to bicarbonate and protons by carbonic anhydrase, preventing a build-up in the concentration of CO2. If carbonic anhydrase is inhibited, however, the system still obeys Le Châtelier's Principle: CO2 is still reacting with H2O to become HCO3- and H+. The problem is that it doesn't react quickly enough, so the CO2 concentration builds up in the tissue (and consumes some H2O in the process; but this point is only minor. As you said @aldol16, water is the biological solvent, and it shouldn't really be considered to increase or decrease in concentration for the MCAT. This point is more so to help @BeerHelpsMeStudy understand why H2O wouldn't increase in concentration).


I hope my reasoning makes more sense now (and is correct).
 
First off, thanks for asking for the clarification. I wasn't sure if my diagram or explanation would be that clear or not, and evidently they aren't. (For an excellent version of the diagram, check the ExamKrackers texbook).

The 'in' refers to inside a red blood cell, while the 'out' refers to outside a red blood cell, which can be plasma, extracellular space, cells, tissues, lungs, etc.

To clarify my reasoning, look specifically at this part of the diagram:

CO2 + H2O -CA-> HCO3- + H+

In the tissues, CO2 is released into the bloodstream, causing this reaction to proceed to the right. (This is reversed in the lungs).

Recall that catalysts, and thus enzymes, only speed up the rate of a reaction, but don't affect the final equilibrium concentrations of products and reactants. In other words, an enzyme just brings a reaction to its equilibrium concentrations (much) faster than if there were no enzyme.
However, even if the the enzyme is inhibited, or not even present, the system will still move towards equilibrium concentrations.

In the case of the bicarbonate buffering system in the tissues, CO2 is being released into the tissues. Under normal conditions, the CO2 is very rapidly converted to bicarbonate and protons by carbonic anhydrase, preventing a build-up in the concentration of CO2. If carbonic anhydrase is inhibited, however, the system still obeys Le Châtelier's Principle: CO2 is still reacting with H2O to become HCO3- and H+. The problem is that it doesn't react quickly enough, so the CO2 concentration builds up in the tissue (and consumes some H2O in the process; but this point is only minor. As you said @aldol16, water is the biological solvent, and it shouldn't really be considered to increase or decrease in concentration for the MCAT. This point is more so to help @BeerHelpsMeStudy understand why H2O wouldn't increase in concentration).


I hope my reasoning makes more sense now (and is correct).

Thanks for your clarification. There is one point in your explanation I have a problem with.

Recall the distinction between the thermodynamics and kinetics of a reaction. An enzyme provides a secondary route that lowers the activation barrier for a given reaction. The whole point of an enzyme is that the reaction will not proceed towards equilibrium at any meaningful rate without it. Take the formation of water from H2 and O2 gas, for instance. That's a pretty exothermic reaction. But you could put hydrogen and oxygen gas in a chamber, come back in a year, and still not have any meaningful amount of water. So one could basically say the reaction does not occur without the enzyme.

I am more familiar with my research in inorganic catalysis, so I'll use another example from that. If you read any JACS or Nature Chem papers pertaining to catalysis in organic synthesis, what you'll find is a common control experiment people do - excluding the catalyst. And invariably, the results they will report are "N.D.", or product not detected without catalyst. What this means is, again, while the overall reaction is thermodynamically favorable, the substrates sit in a potential well and cannot escape in any useful sense of the term.

This example kind of brings up what probability means and what it means to react or not to react. One could imagine a single hydrogen atom. There exists a non-zero and finite probability distribution for hydrogen atom electrons out to infinity. In other words, the electron of a hydrogen atom here could be in a different star system. An extreme example, sure, but you would agree that it's not practical to think of an electron that way. That's why we draw 90% probability limits to generate our "orbitals."

I have digressed from the point, but let me reinforce it here. Without the catalyst, the reaction does not proceed to a measurable or meaningful extent. Otherwise, HIV integrase and protease inhibitors wouldn't work. The virus would still be able to integrate its genome into the host genome and cleave its proteins post-translationally. Therefore, talking about equilibrium is not useful - at least, not until a catalyst makes a path to equilibrium possible for the system.
 
  • Like
Reactions: 1 user
Top