Important - Please read this before you turn the page.
1. (10 Points)
Describe in words and chemical structures the reaction catalyzed by trypsin.
2. (6 Points)
Examine the structures of hematin and bilirubin, a breakdown product of
hematin, below. Show on the structures where bond(s) in heme must be broken
and indicate any atoms that are lost in forming bilirubin. Indicate the
atoms, if any, that are added to bilirubin in the breakdown of hematin.
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Bonus Point: What symptom indicates an accumulation of bilirubin in the human body?
3. (10 Points) If 10% of the people in an African village of 200 are heterozygous for the sickle cell gene (have the "trait" but not anemia), estimate how likely is it that there is at least one person in the village who has sickle cell anemia? Show or describe your thinking.
4. (10 Points) HbC is a fairly common electrophoretic variant of hemoglobin found in the African American population. As shown by the handout in class, the migration of HbC in electrophoresis suggests that it has two more positive charges than HbS and four more positive charges than HbA. Consistent with this, HbC has a lysine in place of glutamic acid (HbA) at position 6 of the beta chain, the same position where valine is found in HbS. We can symbolically represent HbA as apha2beta2, HbC as alpha2beta2Glu6Lys and HbS as alph2beta2Glu6Val.
Consider that you have discovered a new hemoglobin variant HbC-Udel which has the same electrophoretic mobility as HbC but it has glutamic acid at position 6 of the beta chain. Discuss conceptually and categorize the various possible ways that HbC-Udel might differ from HbA.
Bonus question I (2 Points) Draw a diagram that clearly shows how one should arrange three trapezoidal tables in 208 Gore Hall to form a table surface in the shape of an equilateral triangle.
Bonus question II (4 points) Accurately draw or describe where to find biochemical journals such as the Journal of Biological Chemistry in the Morris Library.
5. (10 Points) People who have sickle cell anemia often receive transfusions from a compatible donor. (Such blood transfusions were not practiced in 1933 when Diggs and coworkers did their study.) Assume that a transfusion has doubled the number of red blood cells per ml of blood in a patient. If a day after the transfusion, you placed a sample of the patient's blood under a sealed microscope slide, observed it immediately, and again 6 and 24 hours later, what would you expect to see? Draw pictures for 0, 6, and 24 hours with explanations below.
0 Hour |
6 Hours |
24 Hours |
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2 Bonus points: How would adding dithionite to the samples at time 0 affect the results?
6. (5 Points) You were asked to attend at least one research seminar during the last half of the semester. Describe one (or more) seminar(s) you attended. What did you learn? What were your reactions to the presentation?
7. Essay (15 Points) Select one of the following three questions to answer thoughtfully.
A cell-free protein-synthesizing system, reconstituted with various components (ribosomes, aminoacylated tRNAs, initiation factors, etc.) from mammalian sources, is strongly dependent on exogenous messenger RNA. 9 to 10S RNAs isolated from duck reticulocytes (A) are translated into duck hemoglobin chains by this system. Likewise, 9 to 10S RNAs from rabbit reticulocytes (B) are translated into rabbit hemoglobin chains. When the system is presented simultaneously with duck and rabbit mRNA (A+B) at equal and saturating concentrations, rabbit hemoglobin synthesis occurs almost exclusively even though the maximal rate of hemoglobin synthesis is relatively unaffected regardless of whether the mRNAs are employed separately or in combination.
A. Construct a table that displays the results described
B. Provide a simple pictorial model to explain what appears to be happening on the molecular level.
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Important - Please read this before you turn the page.
• Each group member must sign his or her name on this page to receive the group grade.
• If you cannot come to consensus, you may submit separate answers for a separate grade that would be substituted for the group grade. In that case do not sign the group exam.
• You may refer to your notes, course reader, handouts, textbook, or graded homework assignments. Reference books in the course library may be consulted briefly and returned..
• Please read the questions carefully and make sure that
you have thought them through with everyone's input before converging on
a solution.
1. (17 Points) Pauling and coworkers observed that heterozygous individuals for the sickle cell gene produce a 40:60 ratio of HbS to HbA, rather than a 50:50 ratio. The following describes an in vitro (cell-free in a test tube) experiment which gave a similar but much more striking result [Schreier et al., European Journal of Biochemistry, 34, 213 (1973)].
A cell-free protein-synthesizing system, reconstituted with various components (ribosomes, aminoacylated tRNAs, initiation factors, etc.) from mammalian sources, is strongly dependent on exogenous messenger RNA. 9 to 10S RNAs isolated from duck reticulocytes (A) are translated into duck hemoglobin chains by this system. Likewise, 9 to 10S RNAs from rabbit reticulocytes (B) are translated into rabbit hemoglobin chains. When the system is presented simultaneously with duck and rabbit mRNA (A+B) at equal and saturating concentrations, rabbit hemoglobin synthesis occurs almost exclusively even though the maximal rate of hemoglobin synthesis is relatively unaffected whether the mRNAs are employed separately or in combination.
A. Construct a table that displays the results described.
B. Provide a simple pictorial model to explain what appears to be happening on the molecular level.
2. (8 Points) Estimate to within one order of magnitude
the number of hemoglobin molecules your body makes every second. Show and
explain the basis for your estimate. Up to three points will be awarded
for a reasonable set up. Five points will be awarded to answers withing
one order of magnitude of the accepted answer. One point will be lost for
each order of magnitude error in the estimate. For example, you would loose
2 points if you were 1000-fold of above or below the actual answer. No
credit for answers a million or more fold off.