BCHS 3304 Lecture Notes - Lecture 14: Fetal Hemoglobin, Sickle-Cell Disease, Surface Charge

1. The dominant motif found in hemoglobin and myoglobin is: a) twisted beta sheet b) beta barrel c) helix-loop-helix d) 7-TM 2. Myoglobin has how many polypeptide chains? A) 1 b) 2 c) 3 d) 4 3. Structurally and functionally, hemoglobin closely resembles a(n) a) transmembrane protein b) mucopolysaccharide c) bile salt d) allosteric enzyme 4. The oxygen binding site in hemoglobin and myoglobin is called: a) BPG b) heme c) proximal-His d) N-terminal carbamate 5. The proximal His residue in hemoglobin and myoglobin binds to which atom or molecule? A) CO2 b) O2 c) Fe d) BPG 6. The distal His residue in hemoglobin and myoglobin binds to which atom or molecule? A) CO2 b) O2 c) Fe d) BPG 7. BPG binds to: a) N-terminal carbamate b) proximal His c) heme group d) central cavity 8. Indirect activity of CO2 is a result of increased concentration of which chemical species? A) BPG b) H+ c) heme iron d) distal His 9. Direct activity of CO2 is a result of binding to which molecular feature? A) the heme group b) the N-terminal ends of the 4 polypeptide chains c) the central cavity d) the proximal His 10. The sigmoidal, cooperative binding curve commonly observed for hemoglobin is a result of: a) competition between CO2 and O2 for heme binding. B) competition between heme and distal His for O2 binding c) competition between BPG and CO2 for binding at the central cavity site d) T to R transition 11. Hemoglobin has a tendency to release its oxygen to the tissues because: a) in this region pH is high and O2 concentrations are low b) in this region both pH and O2 concentrations are low c) in this region both pH and O2 concentrations are high d) there is much BPG in this region 12. Which statement about fetal hemoglobin is not true? A) fetal hemoglobin has gamma chains instead of beta chains b) fetal hemoglobin binds BPG less strongly than maternal hemoglobin c) fetal hemoglobin binds oxygen less strongly than maternal hemoglobin d) fetal hemoglobin binds oxygen more strongly than maternal hemoglobin 13. Which process is most responsible for the sickling of cells seen in sickle cell disease? A) aggregation of the oxygenated R form of hemoglobin-S to form insoluble fibers b) aggregation of the deoxygenated T form of hemoglobin-S to form insoluble fibers c) Hemoglobin-S does not contain heme d) Hemoglobin-S contains a mutant form of heme which will not bind oxygen 14. A person with sickle-cell trait is very unlikely to catch which disease? A) malaria b) colon cancer c) avian flu d) whooping cough 15. A person with a genetic defect which results in the synthesis of an insufficient amount of the alpha chain of hemoglobin is said to have which disease? A) alpha thalassemia b) beta thalassemia c) pernicious anemia d) Crohn’s disease

Explain why gelatin, which is mostly collagen, is nutritionally inferior to other types of proteins.

Globular proteins are typically constructed from several layers of secondary structure, with a hydrophobic core and a hydrophylic surface. Is this true for a fibrous protein such as B-keratin?

Briefly explain your answers for the following questions.

a) Is Trp or Gln more likely to be on a protein’s surface?

b) Is Ser or Val less likely to be in a protein’s interior?

c) Is Leu or Ile less likely to be found in a middle of an a-helix?

d) Is Cys or Ser more likely to be in a B-sheet?

You are performing site-directed mutagenesis to test predictions about which residues are essential for a protein’s function. Which of each pair of amino acid substitutions listed below would you expect to disrupt protein structure the most? Explain.

a) valine replaced by either alanine or phenylalanine

b) lysine replaced by either aspartate or arginine

c) glutamine replaced by either glutamate or asparagine

d) proline replaced by either histidine or glycine

Which of the polypeptide chains below is most likely to form an a-helix? Explain . Which polypeptide chain in would most likely to form a B-strand? Explain

a) CRAGNRKIVLETY

b) SEDNFGAPKSILW

c) QKASVEMAVRNSG

Calculate the p50 value for hemoglobin if YO2 = 0.82 when pO2 = 25 torr.

Explain why long-distance runners prefer to train at high altitude even when the race is to be held at sea level. Why must the runners spend more than a day or two at the higher altitude?

Is the p50 higher or lower than normal in

a) hemoglobin Yakima?

b) hemoglobin Kansas?

In hemoglobin Rainier, tyrosine 145 B is replaced by cysteine, which forms a disulfide bond with another cysteine residue in the same subunit. This prevents the formation of ion pairs that normally would stabilize the T state. How does hemoglobin Ranier differ from normal hemoglobin with respect to a) oxygen affinity, b) the Bohr effect and c) the Hill constant?