TBR Bio Ch. 7 #55

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ajumobim

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The pKa values for the side chain carboxyl groups on aspartic acid and glutamic acid are usually cited as 3.9 and 4.1, respectively. Analysis of lysozyme's active site indicates that the pKa of Asp 52 is still about 3.9, but the pKa of Glu 35 is now about 6.6. Glu 35 shows a 2.5 fold increase in pKa, because:

A) the carboxyl group of Asp 52 is located in a polar environment B) the ionized carboxyl group of Asp 52 destabilizes the protonated carboxyl group of Glu 35 C) the carboxyl group of Glu 35 is located in a nonpolar environment D) the carboxyl group of Glu 35 is located in a polar environment, where it is stabilized by hydrogen bonding

The explanation says that since the pKa of the glutamic acid has increased by 2.5 times, while the pKa of the aspartic acid has not changed, which tells us that Asp 52 is in a polar environment, and that Glu 35 is in a nonpolar environment. How do we get that Glu 35 is nonpolar based on the fact that the pKa has increased to 6.6?

Then, it goes on to say that "in order to remove the dissociable hydrogen from the side chain of Glu-35, the active site must be at a pH close to a pKa of 6.6." Why does Glu-35 have a dissociable hydrogen when it is supposed to be charged? Also, I thought pH at the equivalence point is where the dissociable hydrogen comes off, not pH=pKa where there is an equal concentration of the conjugate base and conjugate acid.

Not following this explanation in the back, has anyone cracked it?

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Actually, C or D may be correct. In this case, I was thinking that D might be the more appropriate answer. Check out the structure of Lysozyme: http://www.fc.up.pt/pessoas/jfgomes/documentos/ArtigosPDF/Hybrid QMMM/figure3.GIF

The pKa of a given functional group is ultimately shaped by the environment it's in. Because we're told the pKa increased (ie. it became less acidic), that tells us something in the environment is making it less likely to get rid of it's proton. According to the picture (3D image of Lysozyme), the carboxyl group of Glu35 is near Arginine (Arg68), a basic aminoacid containing an R group with a high pKa. Therefore its R group would exist primarily in its protonated form (carrying a positive charge). This + charge would stabilize the carboxyl hydrogen of Glu35, making it more difficult to dissociate and thereby cause an increase in the pKa. You could also reason this by saying that if Glu35 where to give up it's proton, the two positive charges would clash, which is unfavorable and unstable.

However, we wouldn't be able to know this unless given a picture or if this detail was included in the passage somewhere. Without knowing, it could have just as easily been because Glu35 was in a nonpolar environment as well (choice C), in which case the resulting positive charge would be less stable, as compared to the positive charge in an aqueous environment (which facilitates hydrogen bonding).

Also, you may want to recall the HH equation to help you with this. For any given pKa value, if the surrounding environment has a pH lower than the pKa, it will exist in a protonated form. When pH=pKa, we are in the buffering region, where 50% exists in the protonated form, while 50% is deprotonated. As we increase pH above the pKa, we shift the to deprotonated form (ie. glutamate - the charged form of glumatic acid). Normal physiological pH is about 7.2, so freely floating glumatic acids in the blood exist predominately in the protonated form since the pH is above the pKa (between 2-3), so that's why most textbooks often present it as a charged species.
 
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