in order for the cells of our body to actually be able to function effectively and efficiently they have to have a large enough supply of oxygen because it's the oxygen that is used in aerobic cellular respiration to produce ATP energy molecules now the hemoglobin molecule is the protein that is responsible for carrying the oxygen from the lungs and to the tissues and cells of our body so if our cells are to function correctly the hemoglobin must be able to bring enough oxygen and release enough oxygen in the tissues of our body and previously we spoke about one allosteric effector molecule namely 2 3 BP gene that binds into the center pocket in that deoxyhemoglobin stabilizing the T state of the deoxyhemoglobin and decreasing the affinity of hemoglobin for oxygen and this is precisely what allows that hemoglobin to basically release enough oxygen to the tissues of our body now as it turns out 2 3 BP G is not the only allosteric effect therefore hemoglobin there are two other molecules found inside our body inside the red blood cells that can bind onto a special region of the hemoglobin other than the oxygen binding side and decrease the affinity of hemoglobin for oxygen thereby shifting the oxygen binding curve to the right side and these two molecules are hydrogen ions and carbon dioxide so once again 2 3 BP G is not the only allosteric effector that improves the efficiency of hemoglobin hydrogen ions and carbon dioxide are also allosteric effectors that increase the amount of oxygen that is released by hemoglobin into exercising tissues of our body and this effect is known as the Bohr effect so the Bohr effect is basically the ability of hydrogen ions and carbon dioxide to bind on to the hemoglobin molecule stabilizing its T state and decreasing its affinity for oxygen thereby shifting the curve to the right side and to see what we mean by this let's take a look at the following diagram so this diagram describes three therefore oxygen binding curves for hemoglobin under three different conditions so the black curve describes the condition in which we don't have any carbon dioxide present and we have a normal pH of 7. 4 which is the pH found inside our lungs the blue curve describes the conditions in which we don't have any carbon dioxide but we decrease our pH so we increase the hydrogen ion concentration to us the pH decreases to about 7. 2 and the red curve describes the condition under which we have about 40 millimeters of mercury of carbon dioxide present in that surrounding area and we also decrease the pH to 7.
2 so once again we increase the hydrogen ion concentration as compared to this case here and notice that when we don't have any co2 present but we lower the pH the black curve actually shifts to the blue position and when we keep the pH a 7. 4 and we add carbon dioxide the blue curve shifts to where the red curve is so we see that hydrogen ions and carbon dioxide together create the Bohr effect which actually shifts that entire oxygen binding curve of hemoglobin towards the right side and what that means is it decreases the affinity of hemoglobin for oxygen and what that means is it allows the hemoglobin to actually unload and release more oxygen to the tissues of our body and to see how much more is actually released let's take a look at this graph so let's begin inside the lung so inside the lungs we basically have a concentration of of about 100 millimeters of mercury so the y-coordinate of all these three different curves is exactly the same it's around 0. 98 which is equivalent to 98% saturation of hemoglobin now when we go into the exercising tissues the concentration of our oxygen drops to about 20 millimeters of mercury and notice that at this particular point we have three different y-coordinates for this black curve the y-coordinate is around 0.
32 for the blue curve the coordinate is around zero point two one and for the red curve the corden point is around zero point one and what that means is for that black curve when we have a pH of seven point four and no carbon dioxide present inside our exercising tissues the hemoglobin will be 32% saturated with oxygen however if we drop the pH to about seven point two and once again no co2 is present now in the exercising tissues the hemoglobin will be able to unload more oxygen because our fractional saturation drops we now have about 20% saturation of hemoglobin and finally if we drop the pH and we increase the concentration of carbon dioxide to about 40 millimeters of mercury then at a partial pressure of 20 millimeters of mercury for oxygen inside the exercising tissues we're going to have 10% saturation of hemoglobin and so these will be the percentages of hemoglobin that are going to be able to unload and release that oxygen so in this particular case the black curve tells us 98% minus 32% gives us 66 percent of the hemoglobin will be able to release the oxygen to the tissues in the case of the absence of carbon dioxide but a lower pH so a higher concentration of hydrogen ion's we're going to be able to unload 98 -21 or 77 percent of that oxygen so 77 percent of the hemoglobin will unload and release that oxygen and finally for this case in the presence of carbon dioxide and a lower pH meaning a higher concentration of h+ ions 88 percent of the hemoglobin we'll be able to unload that oxygen so we see not only does 2/3 BPG shift the curve to the right side and lower the affinity of hemoglobin for oxygen but so does the hydrogen ion concentration and the carbon dioxide concentration and these three molecules - 3 BP g H+ ions and co2 molecules together create a very effective hemoglobin molecule that is able to actually unload a lot of those many of those oxygen molecules to the tissues of our body so a higher concentration of co2 and a lower pH meaning a higher amount of h+ ions because remember as we increase the H+ ions we decrease our pH so these two things shift the curve to the right thereby decreasing the affinity of hemoglobin for oxygen and allowing the hemoglobin to unload or release more of those oxygen molecules into the exercising tissues the cells of our body now how does this actually take place so let's begin with the pH effect and let's focus on this blue curve here so as of now we're not focusing on increasing or decreasing the co2 concentration we're only increasing we're only focusing on the pH effect increasing the H+ ion so why is it that when we increase the H+ ions in the red blood cells and in our blood system why is it that the curve shifts to the right how do these H+ ions actually effect that hemoglobin molecule well it turns out that in the Hema in the hemoglobin molecule we have several groups that can actually bind H+ ion so one of the group is basically the terminal residue the amino group on the terminal residue of the alpha subunits and the other group are the histidine residues found on the beta 146 position and the alpha 122 position so these groups on the hemoglobin molecule can actually bind H+ ions and by binding H+ ions those ions can then participate in forming stabilizing soul bridges and to see what we mean by that let's take a look at the following diagram so this is the histidine 141 residue found on the beta 1 subunit and this is a nearby residue on the same beta 1 subunit the aspartate 94 now notice in this particular case so at a relatively high pH of let's say 7. 4 which is the pH inside our lungs this nitrogen so by the way this is the nitrogen these are carbons and these are blue ones are oxygen molecules a'junk are atoms and this orange one is an H ion so basically this is the histidine residue and this is the aspartate residue and at a relatively high pH so let's say at the normal pH of 7. 4 the pH is not low enough to actually add an H+ ion onto this nitrogen and so this nitrogen will be missing an H+ ion and no bond will be formed between these two groups but as we lower the pH and increase the concentration of the H+ ions now we approach the pKa value of this residue which is about 7 7 and so what that means is we have enough H+ ions so that the H+ ions can protonate this nitrogen and by protonating this nitrogen we basically create this nitrogen hydrogen bond and now the hydrogen which bears our partial positive charge can interact with the negatively charged oxygen atom of the of the sidechain of the aspartate 94 amino acid and this forms a Sol bridge ass old bridge is basically a stabilizing electric interaction between these two adjacent atoms and by forming this Sol bridge we essentially decrease the net charge in that localized region and that stabilizes the T State the tenth state of that deoxyhemoglobin molecule and what that does is it lowers the affinity of hemoglobin for oxygen and makes it more likely to unload that oxygen to the tissues of our body and that means it shifts the entire curve to the right side and that's precisely why when we go from no co2 pH of 7.
4 to no co2 and the pH of 7.
