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1. Hemoglobin contains two alpha and two beta subunits, each carrying one heme molecule. Binding of an oxygen molecule by one subunit causes a slight conformational change in the subunit that causes a slight quaternary change that causes an adjacent subunit to bind oxygen with greater affinity. This is referred to as cooperativity.
2. Cooperativity requires multiple subunits. Myoglobin, which has only one subunit, does not exhibit cooperativity. Thus, myoglobin's affinity for oxygen does not change as the oxygen concentration changes. This is not a good property for carrying oxygen, but is great for storing oxygen. It is for these reasons that myoglobin is used to store oxygen and hemoglobin is used to carry oxygen.
3. When hemoglobin is in the state of high affinity for oxygen (wants to bind oyxgen), we say it is in the R state. When it is in the low affinity state for oxygen (wants to release oxygen), we say it is in the T state.
4. Adult hemoglobin contains a tiny pocket in the middle of it that can bind a molecule called 2,3 BPG (also called BPG). 2,3 BPG is produced by actively respiring tissues. When it is bound, hemoglobin loses some affinity for its oxygen (changes to T state) and lets it go. Hemoglobin drops BPG before it gets to the lungs and it is broken down readily, if you're not a smoker.
5. In smokers, BPG is in greater abundance in the blood, so hemoglobin has reduced oxygen carrying capacity, due to more of it coming to the lungs bound to 2,3 BPG and is thus locked in the T state.
6. The Bohr effect relates to the fact that hemoglobin loses affinity for (lets go of) oxygen the more acidic the environment in which the hemoglobin is found. Any tissue, such as muscles, when actively using energy, produces acid. Active tissues require more oxygen than non-active tissues, as we will see later in the course. Thus active tissues get more oxygen dumped on them by hemoglobin, due to the Bohr effect.
7. CO2 is a byproduct of active tissues. When hemoglobin picks up protons near active tissues, it dumps the oxygen and picks up CO2, which it transports it back to the lungs. In the lungs, the protons and CO2 come off. They are actually forced off due to the high oxygen concentration. When CO2 comes off, it is exhaled.
8. Binding of CO2 by hemoglobin also favors the release of oxygen.
9. Fetal hemoglobin differs from adult hemoglobin in that the two beta subunits are replaced by two gamma subunits. This changes hemoglobin's structure very slightly so that 2,3BPG can't bind. Consequently, fetal hemoglobin spends more time in the R state and has greater affinity for oxygen so it can take oxygen away from adult hemoglobin.
10. Sickle cell anemia arises from a mutation in one of the hemoglobin subunits. This mutation causes hemoglobin to polymerize under low oxygen conditions and converts the blood cells into a sickle shape. They get stuck in capillaries when this happens, causing severe pain and, in some cases, death.
11. Mutation of the hemoglobin gene, such as is found in sickle cell anemia appears to have a protective effect when heterozygous because it appears to decrease the incidence of death from malaria in youths.
12. The following forces stabilize protein structure
Primary = peptide bonds (covalent)
Secondary = hydrogen bonds
Tertiary = hydrogen bonds, ionic interactions, hydrophobic interactions, covalent (disulfide) bonds, ionic interactions, metallic bonds
Quaternary = hydrogen bonds, ionic interactions, hydrophobic interactions, covalent (disulfide) bonds, ionic interactions, metallic bonds
13. It is extraordinarily difficult to impossible to predict the precise 3D strucutre of a protein simply from the primary sequence, though secondary structure can be predicted with reasonable accuracy.
14. Misfolding of proteins is a factor in diseases such as mad cow disease or a human disesase called Creutzfeld-Jacob disease. These misfolded proteins are normal brain proteins and are called prions when they fold improperly. Cells have protections against misfolding in the form of complexes called chaperonins.