2,3BPG & Smoking. When the carve is shifted to the right decreasing in O2 binging affinity b.c the change in the shape &function

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2 Where do protons bind to Hemoglobin? It could bind in dissociated carboxyl group in Hb or in dissociate amino group ( NH+3, COOH ) Protons change Hb shape, How? Once proton bind to Hb it will produce + charge ( NH+3 ) or cancel the negative charge in carboxyl group, so it possible to positive charge come near negative or positive charge then produce some electrostatic effect on tertiary structure Hb SO shape change & function & upload O2 Revision : 1. Acid release O2 from Hb 2. CO2 release O2 from Hb 3. Protons release O2 from Hb 4. When have two factor from above find together there will be double / synergistic effect of high unloading to O2 from Hb 5. 2,3 BPG release O2 also 2, 3 BPG 1. Byproduct of Glycolysis 2. Exercising Muscle Cells Rapid Use Glycolysis 3. Exercising Muscle Cells Produce Acid, CO2, and 2,3 BPG 4. Binds in Hole of Donut 5. Locks Hemoglobin in T-State 2,3BPG side product in glycolysis not intermediate product In exercising muscle there a lot of 2,3BPG because the glycolysis active Where does the 2,3 BPG bind in Myoglobin?? It doesn't bind anywhere, b.c it doesn t have hole,its monomer & composed from one subunit Page 1

3 Slowly metabolizing Rapidly metabolizing Rapidly Metabolizing Cells Produce Acid Rapidly Metabolizing Cells Release CO 2 Rapidly Metabolizing Cells Release 2,3 BPG All Favor O 2 Release from Hemoglobin So Rapidly Metabolizing Cells Get More O 2 When the carve is shifted to the right decreasing in O2 binging affinity b.c the change in the shape &function 2,3BPG & Smoking 1. BPG Big Concern for Smokers 2. Blood of Smokers has High Levels of 2,3 BPG 3. Hemoglobin Gets Locked in T-state ( which is not favor O2 binding ) in Passage Through Lungs when binding with 2,3BPG,so little or no O2 will be binding in Hb in the lung 4. Oxygen Carrying Capacity of Blood Reduced because it is negative effector so decrease O2 binding affinity so 02 reduced 5. Carbon Monoxide Levels Also Higher in Smokers in high concentration of CO it will replace O2 in Hb, so those people will die (HIGH CO NO O2 IN Hb NO ENERGY DEATH) Binding of CO with iron in Hb, will be reduced, because of globin which has another histidine called proximal histidine will reduced CO to binding O2 Page 2

4 Co2 bond to Hb & O2 will be release Co2 in the blood will be converted to carbonic acid then in the present of oxygenated Hb will be bond with CO2 & it will be dissociated as COO- While CO2 in the lung will be some exchange with O2 & CO2 will be release Carbon Monoxide and Heme An Additional Histidine is Present at the Heme Iron Site Reduces Affinity to CO, but Does Not Eliminate it Carbon Monoxide in Cigarette Smoke Note That CO 2Does Not Bind to Heme, nor do Protons Page 3

5 Fetal Hemoglobin The development of Hb :- Embryonic Hb then converted to Fetal Hemoglobin then to adult Hb 1. Embryonic Hb :- compose of embryonic goblin genes ( b light & a light ) 2. Fetal Hb :- fetal globin (Y2 light) & a globin genes 3. Adult Hb A & b increases and the ᵟ started in adult levels Affinity of O2 binding of fetal is the higher but it also releases O2 in little amount Fetal Hb found in uterus Adult Hb have very low O2 binding affinity b.c it compound of GLOBIN A للتوض ح : اله موغلوب ن ف المرحلة الجن ن ة تكون من a2 & y2 بدل الب تا بالتال قدرته على االرتباط باالكسج ن تكون عال ة بح ث لما قترب دم االم من دم الجن ن كون قادر على االرتباط باكبر كم ة ممكنة من االكسج ن علما انه اله موغلوب ن ف مرحلة البلوغ ( عند االم ) حوي على الب تا لذلك ارتباطه باالكسج ن اقل ما مكن مما سهل انتقاله للجن ن و بالرغم من قدرة اله موغلوب ن الجن ن fetal Hb عال ة ف االرتباط باالكسج ن اال انه فقد االكسج ن بكم ات بس طة هذه الفكرة ف الر كورد من )23,62 63( لمن لم فهمها ج دا Page 4

6 Fetal Hemoglobin Can t Bind to 2,6 BPG Mostly Remains in R-state Sickle Cell Anemia Sickle Cell Anemia is a Genetic Disease Affecting Hemoglobin Multiple Forms - Mutation of Glu to Val at Position #6in Beta globin gene. Most Common Red Blood Cells Lose Rounded Shape and Form Sickles Shape Change Happens in Low O2 Conditions - Exercise Change Caused by Polymerization of Hemoglobin Sickle Cell Anemia Rounded Cells Move Easily Through Capillaries Sickled Cells Get Stuck Sickled Cells Removed by Spleen The sickle cells will accumulate and block the capillaries of the arteries thus oxygen will not reach the tissues they supply and the tissues will die and when they are stuck in spleen and being removed the blood will lack RBC'S and thus anemia happens sickle cell is considered as a protective agent against Malaria Most of our hemoglobin is hemoglobin a which represent 98% of our hemoglobin. Sickle Cell Anemia Benefit of Sickle Cell Mutation for Heterozygotes No Benefit to Homozygous Recessive or Dominant Page 5

7 Summary Animals Have Widely Varying O2 Needs ATP Generated Much More Efficiently in Presence of O2 Hemoglobin and Myoglobin are Related, but Have Different Functions Hemoglobin has Four Subunits and Hemes. Myoglobin has One of Each Bind of O2 by Heme s Iron Pulls up on a Histidine and Change s Hemoglobin s Shape Changing Hemoglobin s Shape Converts Hemoglobin from T-state to R- state R-state Binds Oxygen Better. T-state Releases O2 Better In the Bohr Effect, Binding of CO2 and H+ Favors O2 Release The Bohr Effect Explains How Oxygen and CO2 Exchanged in Lungs 2,3 BPG is Produced by Rapidly Metabolizing Cells. It too Favors O2 Release Fetal Hemoglobin Can t Bind 2,6 BPG and has Greater O2 Affinity Than Adult Hemoglobin Sickle Cell Anemia (SCA) is a Genetic Disease of Hemoglobin In Low O2 Concentration, Red Blood Cells of SCA Sufferers Form Sickle Shapes Sickled Cells Stick in Capillaries and Can be Fatal People Heterozygous for the Mutated Gene Survive Malaria Better Than Others GOOD LUCK Page 6