friday 10 7 05

Lecture 10/7/05
• {Recap from last week: figure 5-14 myoglobin behaves ideally as a constant and hemoglobin does not because it has a variable.}
• Figure 5-12 myoglobin behaves as a rectangular hypotenuse. Hemoglobin is s shape, which tells us that it is undergoing dynamic changes and the default is less active. We will see where proteins go from active to less active, meaning maximum binging is lower.
• Physical controls: myoglobin is in skeletal tissue. Hemoglobin is a transporter of oxygen from lungs (high pressure) to tissues (resting state has a lower pressure).
• Hemoglobin is completed saturated at high levels. It is used up in lower pressures, where the tissue tries to get out as much oxygen as possible.
• Myoglobin does not let go of its oxygen as easy because there is no change in binding ability with the pressure difference. Only about 1% is let go
• Hemoglobin unloads about 40% of its oxygen with each circulation, this is maximizing its use of 4 heme.
• Figure 5-11 dexoyhemoglobin is the T state, oxygenated hemoglobin is the R state. There are dynamic changes between the two states.
• Figure 5-8 With dexoyhemoglobin the interface between alpha 1/beta 1 and alpha 2/beta 2 is very stable because there are many different types of bonds between the subunits. It is the change between the alpha 1/beta 2 and alpha 2/beta 1 that is most evident and changes the hemoglobin from T state to R state.
• Figure 5-9 The T state can be thought as the tension state, because the bonds are very tense. The R state can be thought as the relaxed state because the bonds are loosened. The c-terminal is histidine which is important because that adds stability. (It is not histidine in embryonic or fetal state.) The ASP is a strong acid (negative) and the HIS is a base (plus) which makes an electrostatic bond. It is this bond that moves the most during the transition between T and R state.
• Figure 5-16 T to R state is responsible to physical changes in oxygen. Also responsible to pH changes and CO2 changes. The more acidic the pH the more it is happy to stay in T form rather than R form. This was discover during WWII and is called the Bohr effect.
• The unfinished folded proteins are different than crystallized protein.
• Because of the interactions happening within the protein, acidic R groups would push away and weaken the bond. Basic R groups would strengthen the bond.
• Hemoglobin mores from acid to base, because the histidine is picking up H+ which encourages heme to bind with Oxygen.
• Figure 5-11 The T state ring is concaved or out of plane. The R state has less stress on heme ring and the iron is in the center. The change happens because the heme group is ½ an angstrom closer in the R state. There are other changes taking place but this is the most important. This is a dynamic process; it is a thermo-active protein. This allows oxygen to bind and create a stable R state.
• Figure 5-15 model shows the possible changes of subunits within a protein, the B picture is the expanded more complicated version.
• Figure 5-16 Side cells are metabolizing and producing acid. Metabolism can take place as anaerobic or aerobic while burning glucose. This lowers the pH, which tells the red blood cells to dump more oxygen. Hemoglobin can also pick up protons from tissue (acidic) can carries it to the lungs(less acidic).
• Hemoglobin also can carry CO2 at the 4 frees amino terminal ends. Push to T form and CO2 is unloaded in the lungs.
• Figure 5-10 and Figure 5-18 the obvious change from T to R state is the hole closing up
• 2-3 Bisphosphoglycerate(BPG) This hole can be filled by 2-3 Bisphosphoglycerate or BPG. It is a polyanion, 3 chances for election accepting. BPG drops in to the hole of T state hemoglobin. It is a product of glucose metabolism. It helps is the transition between R to T state by pushing out oxygen. This allows tissue to be more aerobic and metabolism is slowed down. More of BPG is produced during anaerobic times, so it acts as a check point to tell the hemoglobin how fast metabolism is happening so it can auto correct itself and get more oxygen to the tissue.
• Figure 5-17 When you climb a mountain you make more BMG. Changes oxygen carrying capacity, loading less and unloading more; makes you feel sick till your body adjusts.
• Figure 5-19 Sickle cell anemia is a single change in the amino acid sequence and it changes the shape and function of hemoglobin.
• Figure 5-20 As shown, it changes the shape of the subunits, and creates a greasy patch. This changes the interaction between them and makes a new fiber formation which reduces blood flow.