Basic Substances more soluble in basic solutions... What? (Princeton)

[JLeBling]

I found this question in Princeton Review Elite: It doesn't seem right.

Cystinuria is an autosomal recessive inherited condition that results in inadequate reabsorption of cystine in the proximal convoluted tubule, thus resulting in excess amounts of this basic amino acid in the urine. Which of the following treatments may help prevent the precipitation of cystine stones?

A. Urine acidification with cranberry juice
B. Urine alkalinization with potassium citrate
C. A diet rich in meat, fish, sausages, eggs, cheese and soy beans
D. Monitoring urine concentration and maintaining a high urine specific gravity

Explanation:
B. As mentioned in the question stem, cystine is a basic amino acid. Basic substances have increased solubility in basic solutions, therefore alkalinization of the urine would be expected to lead to increased cystine solubility and therefore decreased cystine stone precipitation (choice B is correct). Potassium citrate is commonly used in patients with cystinuria for this mechanism. Urine acidification would create the opposite conditions and would likely lead to increased cystine precipitation (choice A is wrong). Meat, fish, sausages, eggs and soy beans are all high-protein foods which would lead to increased amino acids and therefore increased cystine. The increased cystine concentration would lead to increased precipitation (choice C is incorrect). Patients with cystinuria are told to avoid these foods for that reason. Another method of decreasing cystine concentration would be to increase fluid consumption, effectively diluting the urine. Dilute urine has a lower specific gravity, and would decrease cystine precipitation (choice D is wrong).

Since when is a basic compound more soluble in a basic solution? Doesn't this violate the common ion effect? Wikipedia actually confirms the explanation given: http://en.wikipedia.org/wiki/Cystinuria#Treatment

So what's up with that?

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[Bru]

Whoops! thought they said cysteine.

 

[HopefulMDclass2020]

bump, interested in answer

 

[sazerac]

Right answer, bad explanation. In a basic environment, the H at the end of the thiol group will fall off, turning the cysteine into a charged thiolate. Ions don't form crystals, so they get peed out, instead of forming stones.

Cysteine is behaving like an acid (proton donor) in this environment.

 

[shefv]

I am confused

So the cysteine aa's have formed disulfide bonds within the proximal convoluted tubules and thus made cystine and are not being properly reabsorbed from the PCT. Since the cysteines have given up H+ (which are being discarded into urine) to make the S-S bonds, we can say that there is basic environment in the PCT. So, shouldn't we be making the conditions in the PCT more acidic to prevent the formation of S-S bonds and thus prevent cystine stones from forming?

Where am I going wrong with my logic here?

 

[StarFall]

Right answer, bad explanation. In a basic environment, the H at the end of the thiol group will fall off, turning the cysteine into a charged thiolate. Ions don't form crystals, so they get peed out, instead of forming stones.

Cysteine is behaving like an acid (proton donor) in this environment.

Wouldn't the base make it favorable to the 2 cysteines to react and form the disulfide bridge, thus making the cystine stone? I'm assuming cysteine is the soluable form and cystine is the insoluable form.

Since reducing the disulfide bridge would make 2 cysteine's, wouldn't we want an acidic environment so the disulfide bridges become protonated?
Also, lowering the pH would mean that cysteine is in it's protonated form (assuming pH < pka of cysteine's S) which is what I thought what we would want.

I am confused

So the cysteine aa's have formed disulfide bonds within the proximal convoluted tubules and thus made cystine and are not being properly reabsorbed from the PCT. Since the cysteines have given up H+ (which are being discarded into urine) to make the S-S bonds, we can say that there is basic environment in the PCT. So, shouldn't we be making the conditions in the PCT more acidic to prevent the formation of S-S bonds and thus prevent cystine stones from forming?

Where am I going wrong with my logic here?

Confused as well, but the cysteines giving up H's would make the filtrate more acidic, but this would be picked up and turned into water, I think. Even so, I think that to prevent S-S bonds forming, we would need to make the environment more acidic so the equibrium would shift towards the 'reactants' or cysteine molecules (S-H) or the acidic environment would provide the H's so the disulfide bridges would be reduced and break, breaking the stones.

 

[RH8448]

Citrate acting as a base would be helpful because it will make the "dipeptide" cysteine more charged and thus more hydrophilic. If protons can be removed from the environment so to speak, this will leave the molecule more charged and able to flow out instead of crystalizing.

This has nothing to do with the di-sulfide covalent bond. That covalent bond cannot be broken down again, at least by minor changes in pH. So we are dealing with cys-cys dipeptide that has four groups that can participate in acid base reactions. A more basic environment will made that dipeptide more charged and unable to precipitate.

Even if we were dealing with a cystine amino acid, a precipitate would be less likely to form because it is not very hydrophobic. Plus the thiol group can hydrogen bond. To deprotonate a thiol group it would also take a very high pH.

This question also refers to this compound we are dealing with as "cysteine" and as "this basic amino acid" A cysteine would not be anymore basic as other amino acids because the R groups is involved in a covalent bond. So I think it is a confusing question.

Please correct me if I am inaccurate, thanks.

 

[RH8448]

"cys-cys" dipeptide would not be a dipeptide but rather just bonded pieces of peptides

 

[Holmwood]

Cysteine is neither acidic or basic, it's polar. TPR is wrong because basic stuff precipitates out of basic stuff and solubilizes in acidic environment.

The formation of cysteine and cystine are in equilbrium: SH + SH > S-S + 2H

You can make two conclusions here:
1) If you make the solution acidic, you increase the H+ favoring the formation of SH. However, SH still remains non polar so it does not change the solubility at all. Therefore, increasing the acidity is not the answer.
2) Because the formation of S-S is problematic, you want to take SH out of the equation and shift the equation towards the left. As -SH group is similar to an -OH group, the hydrogen can be taken out if the environment is sufficiently basic. By converting more SH to negatively charged S, you will shift the equation to the left preventing the formation of S-S.