Dr. Rosen reappeared in the cubicle. “Sorry for the interruption, and for leaving you in suspense. The good news is that you did not have a heart attack. But I do think you’re having an unusual reaction to Topamax. It appears to be inhibiting your renal carbonic anhydrase, leading to metabolic acidosis. We’ll be giving you an IV, and you should taper off your Topamax under your family physician’s supervision.”
Dr. Rosen checked his pager and said, “Sorry, it’s one of those days. Again, you’ll be all right, and the nurse will be with you shortly to start the IV.” He turned on his heel and left just as quickly as he had appeared.
“Mom, don’t worry,” said Chris. “I’m going to call one of my friends studying biochemistry. He should be able to help us figure this out.”
Chris dials his cell phone; yours rings. After you complete the following questions, write a one- or two-paragraph explanation to help Chris understand what’s going on with his mom.
2a. Bicarbonate is one of the main buffers in the blood. Provide a definition of a buffer.
2b. Give an equation that allows one to calculate the pH of a buffer solution.
2c. The pKa’s for carbonic acid and bicarbonate at 37°C are 3.83 and 10.25, respectively.
i. Write the equation for each of these equilibria.
ii. Below is a titration curve for carbonic acid. Indicate key points on the curve, such as equivalence points and buffer regions. At what pH(s) would you expect carbonic acid species to have effective buffering capacity? Explain.

iii. Calculate the ratio of bicarbonate to carbonic acid at pH 7.4, using the pKa value(s) in 2c.
iv. What is unusual about these ratios? Would you expect this to be an effective buffer system at pH 7.4? Explain.
2d. Bicarbonate does buffer the blood because carbonic acid is generated from dissolving CO2 (g) in liquid water:
CO2 (g) + H2O (l)
H2CO3 (aq) pKeq° = 2.52 at 37°C
This reaction is catalyzed by the enzyme carbonic anhydrase. Consequently, the reaction that really represents what’s happening when bicarbonate buffers the blood is:
CO2 (g) + H2O (l)
HCO3- (aq) + H+ (aq).
Calculate the equilibrium constant for this reaction (Hint: use Hess’s law and one of the equilibrium expressions from question 2ci above). Would you expect this to be an adequate buffer system at physiological pH? Explain.
Originally published at http://www.sciencecases.org/topiramate/biochem_case2.asp
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