in the previous video we talked about the difference between hemoglobin and myoglobin in terms of structural rules and accident situation curves we also discussed the toka information of hemoglobin in this video we will talk about the allosteric effectors of hemoglobin before we start talking about anesthetic effectors you must tell that hemoglobin is an allosteric protein what that mean is hemoglobin has two receptor sites one photolytic and and one for the allosteric effectors and when an allosteric effector bond to a protein it induces a conformational change in the protein structure affecting the ligand affinity in a positive or negative way depending on the type of the effector molecule for example when a positive allosteric effector bond so a protein it induces a change in the protein structure making the active soil available for the ligand but when a negative allosteric effector binds to a protein it induces a change in its structure making the active site and available for delicate in hemoglobin oxygen is the ligand and when an activator or a positive allosteric effector binds to hemoglobin it induces a conformational change in hemoglobin structure increasing its affinity to bind more oxygen and such stabilizing the relaxed state knowing that the r-state of hemoglobin has the highest affinity for oxygen please refer the previous video for more details about the hemoglobin confirmations and when a negative allosteric effector also known as inhibitor binds to hemoglobin it induces a conformational change in human structure decreasing its affinity for oxygen and thus stabilizing the tongue state understand if factors can also be classified as holotropic and heterotrophic in case of homotopic effectors the nickens add as an like effector for example binding of an oxygen at one side of hemoglobin increases the affinity of hemoglobin for binding oxygen at another side shifting the hemoglobin conformation from tip to our state and we said previously that when an effector increases the affinity for delegate it's called a positive factor so oxygen is a positive homo tropic a factor whereas when a substance other than the ligand act as an allosteric effector such as the proton the carbon dioxide a molecule called 2.3 by phosphoglycerate we call them heterotopic allosteric effectors next we will see how these effectors will decrease the oxygen binding affinity for amok of the hemoglobin and thus they will be considered as negative hydroscopic effectors in the next slides we will talk about how each of these types of tropic is factors will affect the hemoglobin binding affinity for oxygen let's start with the head tropic effect of protein but before that you have to keep in mind that hemoglobin exists only in two confirmations a high affinity our state and a low affinity T State and when the partial pressure of oxygen is high as in the lungs the our state of hemoglobin is favored along the maximum amount of oxygen to be bound to the hands in the capillaries where the oxygen concentration levels are lower the t state of hemoglobin is favored in order to facilitate the delivery of oxygen to the tissues so what happens in acidic environment such as in the case of actively metabolizing tissues releasing proteins this released protons will bind to oxygen ooh globin in red blood cells promoting the release of oxygen from hemoglobin the tissues stabilizing the T State in fact when the proton by to hemoglobin it protonates the imidazole group of histidine that participate in a salt bridge with a negatively charged aspartate the formation of this ionic bond holds the structure of hemoglobin together stabilizing the t-state of hemoglobin now let's see how the protein binding to hemoglobin will influence the absence of cherishing curve in acidosis when the pH is low due to high concentration of h+ the affinity of remarkable for oxygen wind decreases so the p50 will increases because they are inversely proportional and this effectively causes shift of the oxygen saturation curve of he moves the second head to tropical aesthetic effect that we're gonna talk about is carbon dioxide co2 is an important and the product of oxidative metabolism so let's see how it will modify the oxygen affinity of him over in fact 70% of co2 released from peripheral tissues is hydrated by carbonic anhydrase - carbonic acid this week as a dissociate partially to h plus and H 2 O 3 - the bicarbonate ion produced moved to plasma in exchange for chloride ions to maintain electroneutrality and this is known as the chloride shift while the regenerated H+ bind to hemoglobin lock we saw in the previous slide stabilize the T State and promote the release of oxygen to tissues 20% of the carbon dioxide react with the amino terminus of the hemoglobin allosteric site to form the carb amino hemoglobin that stabilizes the T State and promote the release of oxygen to dishes and the remaining 10% of co2 will be the souls in plasma so what we conclude is that when the partial pressure of carbon dioxide increases the affinity of hemoglobin for oxygen will decrease and thus the T State of hemoglobin will be stabilized now let's see how the binding of carbon dioxide to hemoglobin will influence the oxygen saturation curve in the following example we have three curves with the different partial pressure of carbon dioxide the green curve has a lowest pitch co2 equal to 20 and the orange curve has the highest pco2 equal to 80 millimeters of mercury as you can see with the partial pressure of carbon dioxide increases from 20 to 40 to 80 millimeters of mercury P 50 which is the partial pressure of oxygen at 50% saturation of hemoglobin when oxygen increases from 23 to 30 to 38 millimeter of mercury respectively shifting the curve to the right so with the partial pressure of co2 increases the affinity of hemoglobin for oxygen decreases the p50 increases and the curve will shift to the right in contrary when the partial pressure of carbon dioxide decreases the affinity of hemoglobin for oxygen increases the partial pressure P 50 decreases and the curves will shift to the left for now we saw that carbon dioxide and hydrogen ions are two heterotopic allosteric effectors of hemoglobin they bind to different sites on the hemoglobin molecule stabilize the T state of hemoglobin and lower its affinity for oxygen this in turn shift the oxygen binding curve to the right side and allow him all clipping to unload more oxygen to the exercising tissue together the effect of hydrogen ions and carbon dioxide on limo globin is known as the Bohr effect next we will talk about the third head tropic allosteric effector the 2.3 by phosphoglycerate 2 or 3 by phosphor glossary instantly ties from an intermediate in the glycolytic pathway in human red blood cells it's a negatively charged molecule that binds to a pocket phoned by two beta globin chains in the center of deoxyhemoglobin stabilizing the Chi state this pocket contains several positively charged amino acids like histidine and lysine that form ionic bonds with a negatively charged phosphate groups of BPG so BPG back to a central pocket empty state of hemoglobin but does it point to our state - well no it doesn't because what happens up in oxygenation is that the two beta chains move closer together leaving unselfish and true for BPG so it cannot bind to hemoglobin or state now let's talk about the importance of BPG and when it's sensitized in fact red blood cells attempt to generate more BPG to help prevent tissue hypoxia in conditions of low tissue oxygen concentration such as high altitude in case of airway obstruction and pregnancy hypoxia so the accumulation of to 3 by phosphoglycerate decreases the affinity of hemoglobin for oxygen when hemoglobin is in sea state and eventually this mechanism increases the oxygen release from red blood cells to tissues let's see how the binding of BPG to hemoglobin will influence the oxygen saturation curve in the following graph we have two curves the pink is for a person on a sea level with a concentration of BP G equal to 5 minimal per liter and the blue curve is for a person adapted to high altitude with a concentration of PPG equal to 8 milli volt per liter as you can see you in the concentration of BP g increases from 5 to 8 million watt per liter the curve will shift to the right so when the concentration of BP g increases the affinity of hemoglobin for oxygen decreases and stabilize the G state of course p50 will increase because the affinity and p50 are inversely proportional and the curve will shift to the right of course when the concentration of the PG decreases the curve will shift to the left and the earth and the r-state of hemoglobin will be stabilized so to summarize in this video we have talked about heterotrophic allosteric effectors of hemoglobin the h plus co2 and v PG all of them were found to decrease the affinity of hemoglobin for oxygen and from a physiological view these negative factors are beneficial since they increase the supply of oxygen to tissues now to list the conditions that shift the hemoglobins curve to the right we have the acidosis due to high concentration of h plus a high partial pressure of co2 and the high raishin of BPG while and alkalosis and aha and the low concentration of co2 and BPG will shift the curve to the left thank you for watching this video if you liked it please like and subscribe