Presentation on theme: "Myoglobin and Hemoglobin"— Presentation transcript:
1 Myoglobin and Hemoglobin Example of Tertiary and Quaternary Structure of ProteinMyoglobin and Hemoglobin
2 MyoglobinWas the first protein the complete tertiary structure was determined by X-tray crystallographyHas 8 α-helical region and no β- pleatedHydrogen binding stabilize the α- helical regionConsist of a single polypeptide chain of 153 a.acid residue and includes prosthetic group- one heme groupStore oxygen as reserve against oxygen deprivation
3 Hemoglobin Example of quaternary structure of protein Consist 4 polypeptide chain -4 subunit- tetramerEach subunit consist one heme group (the same found in myoglobin)The chain interact with each other through noncovalent interaction – electrostatic interaction, hydrogen bonds, and hydrophobic interactionany changes in structure of protein- will cause drastic changes to its propertythis condition is called allostery
4 Hemoglobin An allosteric protein Tetramer, 4 polypeptide chains (α2β2) - 2α-chains and 2β-chains – nothing to do with αhelix and βsheet- its just a greek nameBind O2 in lungs and transport it to cellsTransport C02 and H+ from tissue to lungsThe same heme group in mb and hbCyanide and carbon monoxide kill because they disrupt the physiologic function of hemoglobin2,3- biphosphoglycerate (BPG) promotes the efficient release of 02
5 Heme Group Mb and Hb contain heme – a prosthetic group Responsible to bind to 02Consist of heterocyclic organic ring (porphyrin) and iron atom (Fe2+)Oxidation of Fe 2t to Fe3+ destroy their biologic activityFe has 6 coordination sites that can form complexation bondsFour are occupied by the N atomsFree heme can bind CO 25,000 times than 02 – how Mb and Hb overcome this problem?
6 Structure of heme group in Mb and HB The perfect orientation for CO binding is when all 3 atoms (Fe, C and O) perpendicular to the to the plane of hemeMb and Hb create hindered environment- do not allow O2 to bind at the required orientation- less affinityThe fifth coordination is occupied by Histidine residue F8The O2 is bound at the 6th coordination site of iron
7 heme groupThe second histidine His E7 – not bound to the heme, but acts a gate to open and closes as oxygen enter the hydrophobic pocketE7 inhibit O2 to bind to perpendicularly to hemeThe presence of His E7 – will force CO to bind at the angle – make it lose it affinity to heme
8 Oxygen saturation in Mb and Hb One molecule of Mb- can bind one molecule 02HB (4 molecule)- can bindO2 bind to HB thru positive cooperativity – when one O2 is bound, it become easier for the next to bindDissociation of one O2 from oxygenated Hb will make the dissociation of 02 from other subunits easier
9 Different form of HBHb is bound to 02- oxyhemoglobin – relaxed (R state)Without 02 – deoxyhb – tense (T) stateIf Fe2+ is oxidized to Fe3+ - unable to bind 02- methemoglobinC0 and NO have higher affinity for heme FE2+ than 02- toxicity
10 Oxygen-saturation curve Myoglobin is showing hyperbolic curve – easily saturated by increment of O2 pressureHb-sigmoidal curve – under the same pressure where Mb already near to saturation, Hb is still ‘struggling’ to catch 02.But, once one 02 bind to the molecule – more will bind to it- cooperativity- increase in saturationSame condition for dissociation of O2Hb will release 02 easily in tissues compare to MB-thus make it a good 02 transporter
11 Bohr Effect Hb also transport CO2 and H+ from tissues to lungs When H+ and C02 bind to Hb- affect the affinity of Hb for oxygen – by altering the 3D structureThe effect of H+ - Bohr EffectNot occur in Mb
12 Bohr effect ↑[H+] – protonation of N terminal in Hb Create a salt bridgeLow affinity of Hb to O2Metabolically active tissues need more 02- they generate more C02 and H+ which causes hemoglobin to release its 02C02 produced in metabolism are in the form of H2CO3→ HCO3- and H+HC03- is transported to lungs and combined with H+→ C02 – exhaledThis process allow fine tuning Ph and level of C02 and 02
13 2,3 Biphosphoglycerate (BPG) An intermediate compound found in glucose metabolism pathwayBind to T state of Hb to stabilize Hb and make it less affinity towards 02- will release 02 to celle:g: animal is quickly transported to mount side at altitude 4500m where the P02 is lower – delivery of 02 to tissue reducedAfter few hours at high altitude- [BPG] in blood increase- decrease affinity of Hb to 02-delivery of O2 to tissues is restoredThe situation is reversed when the animal is returned to the sea level
14 2,3 Biphosphoglycerate (BPG) BPG also play role in supplying growing fetus with oxygenFetus must extract oxygen from its mother’s blood- Fetal Hb (HbF) must have higher affinity than the maternal Hb (HbA) for 02HbF has α2γ2 subunitThis s/u has lower affinity towards BPG - higher affinity to O2 compare to HbA
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