User:Eric Martz/Hemoglobin Quiz

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Hemoglobin Quiz

You will get immediate feedback when you click Submit (at the bottom of the quiz). The quiz below is offered to accompany the interactive tutorial Hemoglobin Molecular Structure. For the green questions within the tutorial, answers are below.

Suggestions to emartz at microbio dot umass dot edu.

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Answers to Questions in the Tutorial

Here are answers to the questions posed in green within the Hemoglobin Molecular Structure Tutorial.

1. The main function of hemoglobin is to transport oxygen from the lungs to tissues throughout the body.
2. Each hemoglobin molecule is made up of four protein chains.
3. Each chain in the hemoglobin molecule has a pocket to hold one heme-iron complex. Thus, there are four heme-iron complexes in each hemoglobin molecule.
4. Each of the heme-iron complexes can bind one O₂ molecule. Thus, each hemoglobin molecule can bind up to eight atoms of oxygen.
5. The four chains that make up one hemoglobin molecule are held together by non-covalent interactions (non-covalent bonds).
6. Each iron atom is held by five nitrogen atoms: four nitrogens in heme, plus one nitrogen in the sidechain of a histidine amino acid.
7. Molecular oxygen binds between iron (Fe⁺⁺) and a nitrogen in the sidechain of histidine. The oxygen-binding histidine is on the opposide side of the iron from the iron-binding histidine.
8. Alpha helices and loops (including turns) make up the alpha and beta chains of hemoglobin. They contain no beta strands or sheets.
9. Hydrogen bonds stabilize the conformation of an alpha helix.
10. Hydrogen bonds are non-covalent bonds.
11. Amphipathic means having one part that is hydrophobic, and another part that is hydrophilic.
12. Hydrophobic (literally "water fearing") means structures that avoid contact with water because such contact is energetically unfavorable. Hydrophobic structures are apolar. In contrast, hydrophilic structures favor contact with water molecules, usually because they can form hydrogen bonds with water. Hydrophilic structures include polar and charged structures.
13. The protein pocket that holds heme is predominantly hydrophobic, as is heme itself. Thus, the avoidance of contact with water is partly what holds the heme in the pocket. The histidine that contacts the iron in heme is an exception, since its sidechain is hydrophilic.
14. Protein chains or domains that are soluble in water, such as the alpha and beta chains of hemoglobin, have hydrophobic cores. Amino acids with hydrophilic sidechains are mostly on the surfaces of these chains.
15. The hydrophobic cores of proteins are devoid of water. It is the avoidance of water that drives amino acids with hydrophobic sidechains to pack together in the core, while the attraction of hydrophilic amino acids to water favors their locations on the surface of the folded protein chain.
16. A slightly acidic pH, around 6.5, increases the partial charges on the sidechains of histidines. This is because their sidechain [pKa's are about 6.5. In contrast, lysine and arginine have full positive charges at any physiological pH because their sidechain pKa's are 11-12, while aspartic acid and glutamic acid have full negative charges at any physiological pH because their sidechain pKa's are about 4.
17. A salt bridge is a pair of opposite charges held together by electrostatic attraction. Oppositely charged amino acid sidechains are generally salt-bridged when their charged atoms are less than 4 Å apart.
18. One histidine (sequence number 87 in the beta chain) binds to iron (Fe⁺⁺), helping to hold the iron and heme in place. The other histidine (sequence number 58 in the beta chain) helps to bind molecular oxygen, and probably also serves as a gate to admit and release oxygen (see text under View 11 in Chapter 2).
19. Nitrogen. The lone-electron pairs of nitrogen are attracted to electron-seeking Fe⁺⁺ and O².
20. When oxygen binds to the Fe⁺⁺ in heme, the Fe⁺⁺ moves into the plane of the heme. This pulls the histidine attached to the iron, which in turn pulls the alpha helix containing that heme, which in turn favors the conformational change of the entire hemoglobin molecule from the low-oxygen-affinity deoxy T state to the higher oxygen-affinity oxy R conformation.
21. The slightly acidic pH of tissues, due in part to CO₂ accumulation, reduces the affinity of hemoglobin for oxygen, fostering the release of the oxygen brought from the lungs. The effect of lower pH is in part because it increases the partial positive charge on His146, favoring its salt bridge with Asp94, which helps to hold hemoglobin in the low-affinity T conformation.
22. Histidine is crucial in breaking the salt bridges that favor the low-affinity conformation. The higher pH in the lungs reduces the partial positive charge on histidine, weakening the salt bridge.
23. DPG binds in a crevice between the beta chains. That crevice is open only in the deoxy conformation. It closes up in the oxy conformation. DPG act like a chock holding the beta chains apart in the low-affinity conformation, facilitating the release of oxygen in tissues.
24. The sickle mutation changes only one amino acid among the 146 in the beta chain. Since there are two beta chains per hemoglobin molecule, two amino acids are changed in each molecule.
25. The sickle mutation puts a hydrophobic valine where a hydrophilic (charged) glutamic acid is present on the surface of the normal, wild type. This makes hemoglobin more hydrophobic on its surface.
26. Most people who have sickle hemoglobin are heterozygotes, with one normal and one mutant gene. Half of their hemoglobin is normal, which largely prevents fiber formation and disease. Homozygotes have only sickle hemoglobin, with no normal hemoglobin to impede fiber formation and disease.
27. Sickle hemoglobin reduces the severity of malaria, although it does not prevent infection. Sickle heterozygotes have an advantage where malaria is endemic. (Malaria actually worsens sickle disease in homozygotes, so they have no advantage.)
28. In sickle homozygotes, the mutant hemoglobin, when deoxygenated, forms chains and fibers stuck together with the mutant hydrophobic amino acid. The fibers distort red blood cells, blocking blood flow (vaso-occlusion) and greatly shortening the lifetime of red blood cells. Vaso-occlusion causes pain and can damage bone, spleen, cause strokes, and impair respiration by damaging lungs. The breaking of red blood cells causes anemia and the excess hemoglobin released free in the blood, which is toxic. The body responds by producing red blood cells faster, which causes problems in bone and liver. For a more complete overview, please see this excellent 8-minute video.