Question: hemoglobin cowtown over a thousand different human hemoglobin variants are...
Over a thousand different human hemoglobin variants are known. Many have altered function. Hemoglobin variants have historically been names for the city in which they were identified. One example is hemoglobin Cowtown (Ft. Worth, Texas). Here is an abridged version of the original case report for this particular variant (Schneider et al. (1979) Am J Clin Pathol 72:1028-1032). The A4 post quiz is based on this report.
A 20 year old white male travelled from Fort Worth to Denver Colorado, on vacation. Shortly after disembarking from the aircraft, he experienced a sever throbbing headache, which was not relieved by analgesics, and which became so unbearable that he and his family decided to return home the following day. To the patient's surprise, after several hours in the pressurized airliner, the headache subsided. Upon his return to Fort Worth, his family physician admitted him to the hospital for investigation.
The results of the physical examination were not remarkable, but the hematologic findings indicated erthrocytosis (increased red blood cells). Other laboratory data showing the following:
|Arterial blood pH||7.39|
|Total blood volume||elevated|
|Packed erythrocyte volume||elevated|
Electrophoresis (proteins moving through a gel according to their net charge in the presence of an electric current) at pH 8.5 showed normal pattern for hemoglobin, but analysis at pH 6 revealed a hemoglobin chain with abnormal mobility. Further testing determined a single His -> Leu substitution in shift for Hb Cowtown relative to normal Hb A. The Bohr effect (a measure of the influence of pH on oxygen affinity) was only half the normal value
QUESTION 3: The mutation in Hb Cowtown results in severe impairment of the Bohr effect, yet does not alter the equilibrium between the R and T states. This is surprising since the carboxyl-terminal residue His B146 is clearly invalid in stabilization of the T state. Deduce the allosteric roles of each ionizable group in the C terminal residue.
|His B146 alpha carboxyl||Answer choices: None, T state stabilization, R state stabilization, Bohr effect|
|His B146 imidazole||Answer choices: None, T state stabilization, R state stabilization or Bohr effect|
|His B146 alpha amine||Answer choices: None, T state stabilization, R state stabilization or Bohr effect|