mrh125

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how to read it and what not, how to determine off-loading and affinity, what the different values mean. for some reason this thing never made much sense to me. I got most of the mcat questions about it right on a practice test just by being a very efficient guesser but i'd rather understand it.

I've also taken biochemistry and this thing still confuses me.

here's what i have after watching a video on it. Anything else major that I'm missing?:
shifting curve to the right - hemoglobin is more apt to release oxygen because it has lower saturation than the regular one. therefore the right shift is more apt to be less saturated at a given po2 (shifts back and forth as it goes through blood stream). less affinity (low pH, high temp, high pco2). higher p50



shifting curve to the left - more apt to bind oxygen. lungs (high ph, low temp, low pco2, fetal hemoglobin) lower p50. higher saturation.
 
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Oct 20, 2013
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To start, it is important to understand the X & Y axes on the graph. The X is partial pressure of oxygen (PO2) in the specific area and the Y is % saturation. At low oxygen concentrations, the percent saturation of oxygen in hemoglobin is low because the oxygen is being released into the low oxygen concentration environment (so this is in muscles/tissue). At high oxygen concentration in the body, hemoglobin is going to want to pick that up in order to bring it to lower oxygen concentrations, so its going to be saturated. So this is in the lungs. The shape of the curve is because the first oxygen picked up causes hemoglobin to change its shape a little so that way the second oxygen can bind more easily, which makes the third easier, which makes the fourth easier. High affinity occurs at high partial pressure so that makes high (100%) saturation. A rightward shift means decreased affinity (because it takes more oxygen to reach saturation), a leftward shift means increased affinity (takes less oxygen to reach saturation).

I didn't really understand the temperature thing before, but the reason why low/high temperatures matter is because low temperature indicates that te body is in rest and thus there is more O2, so there is a greater affinity. At high temperatures, the body is active and thus there is less oxygen and the rightward shift. A decrease in pH really means an increase in CO2, which is which shifts the curve to the right. There's an equation that explains this...also basically when H+ binds to hemoglobin, it causes a release of the O2, so a lower pH causes decreased affinity and a rightward shift.

One thing that you might see is 2,3-bisphosphoglycerate (BPG), which has effects similar to H+ and CO2 and thus decreases affinity and causes a rightward shift. Smokers have increased BPG. BPG in the blood also rises at high altitude, which makes it harder for hemoglobin to deliver oxygen. Fetal hemoglobin is more resistant to BPG.
 
Oct 27, 2014
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This is an old bump, but people are going to be looking this up and I think it's important to correct misinformation. pjk77, everything above is good about your post except for when you mention that increased BPG causes a rightward shift that makes it harder for hemoglobin to deliver oxygen. A rightward shift, or increased Km, causes a decreased affinity at the hemoglobin. Decreased affinity corresponds to an INCREASED ability for oxygen to be delivered to the tissues. A rise in BPG is a compensatory mechanism at higher altitudes for tissues to be able to get the oxygen they need, and the same applies to smokers. Think about it, does it make ANY sense for the body to make it HARDER to deliver oxygen to tissues because the body has a decreased concentration of oxygen available? No! We are control freaks, and you bet our bodies will do everything in its power to make sure we keep up with that oxygen demand.

This is VERY important not to mix up for the new MCAT because you need to know that a decreased affinity corresponds to areas in the body that are under high metabolic demand. At tissues with high CO2, low, PH, high temp, and low oxygen, there will generally be a high Km or low affinity for oxygen that will enable oxygen to be more efficiently delivered to tissues to keep up with demand. The reason that low affinity corresponds to increased delivery is because the tissue is more easily to pick something up when hemoglobin has a lower affinity/lesser desire to hold on to oxygen.

Edit: to address this concern: what about a decreased affinity for hemoglobin to pickup oxygen in the lungs? You have to think that the concentration or PO2 of oxygen in the lungs is less pertinent in a healthy individual because there is plenty of oxygen available there. The real issue corresponds to giving that oxygen up in the blood. The tissues that need oxygen most will require a compensatory mechanism when there is a decreased availability of oxygen. And trust me, your lungs are getting plenty of oxygen even at high altitudes. The problem is those other tissues!

As you can see, there is a common trend here you need to understand for MCAT 2015.
 
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kingtal0n

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A way to get this down is to consider affinities for other types of molecules and systems. For instance, in the hepatic portal vein their is a glucose transporter known as GLUT 2. It has a low affinity for glucose because this allows it to offload at the liver much easier,

If GLUT4 is a protein transporter for glucose then it must have a high affinity for glucose on one side, and a low affinity for it in an alternative conformation on the other side of a membrane
 
Jan 12, 2015
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One way to make sense of this is to think about a pregnant woman delivering oxygen to the fetus. Fetal hemoglobin must have a high affinity for O2 so that O2 can be delivered from the mother to the fetus. A high affinity means a lower Km implying a leftward shift in curve.

It also makes sense that Km will increase when out body needs more oxygen. When our body needs more oxygen its usually because we are exerting ourselves. We become hot when we work out making us unload higher amounts of oxygen. We aren't able to exhale all of our CO2 so our pH decreases, again increasing our Km for O2 on hemoglobin. I'm sure many other molecules like 2,3 BPG (that does make "O2 unloading more easy" are involved in changing this curve.

But generally speaking you need to know the ones mentioned. Most importantly, you need to understand why. This is because we need to know how to make sense of what we don't know yet.
 
Oct 27, 2014
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If GLUT4 is a protein transporter for glucose then it must have a high affinity for glucose on one side, and a low affinity for it in an alternative conformation on the other side of a membrane
Thanks. I agree. I shouldn't of added the portion about other molecules, because now I can see how that'd make the concept more complex to understand. It's important to consider that hemoglobin is free in the blood, while the transporter is embedded in the membrane. If the affinity for oxygen is low for hemoglobin, the oxygen can more easily perfuse into cells because hemoglobin is less interested in oxygen. Therefore, the cell will more likely contain a greater affinity for oxygen than hemoglobin.



In regards to GLUT 4: GLUT 4 has a high affinity. Glucose transporters will be saturated when glucose concentration is jut a little elevated. The concentration of glucose will more easily exceed the Km. Thus, the rate at which the cells pickup glucose will be constant. (zero-order kinetics).

In regards to GLUT 2: GLUT 2 has a low affinity. The concentration of glucose will less easily exceed the Km. Thus, GLUT 2 will pickup glucose corresponding to the concentration in the circulation. This is first-order kinetics. You need to have your Km straights for this exam! When the concentration of glucose drops below the Km, much of the remainder will leave the liver and enter the peripheral circulation. When glucose concentration exceeds Km will the glucose make its way into the liver. Glucose, in other words, will be picked up after a meal (rich in carbs) when glucose levels are elevated.

I went ahead and deleted the latter portion of that post as not to confuse others.
 
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