1 / 25

Oxygen Binding Proteins

Oxygen Binding Proteins. Oxygen Binding Proteins are Hemoproteins. Oxygen binding proteins ( myoglobin and hemoglobin) are hemoproteins Hemoproteins are a group of specialized proteins that contain heme as a tightly bound prosthetic group.

ruana
Télécharger la présentation

Oxygen Binding Proteins

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript

  1. Oxygen Binding Proteins

  2. Oxygen Binding Proteins are Hemoproteins • Oxygen binding proteins (myoglobin and hemoglobin) are hemoproteins • Hemoproteinsare a group of specialized proteins that contain heme as a tightly bound prosthetic group. • Heme is a complex of protoporphyrinIX & ferrous iron (Fe2+) . • Heme Fe2+ is held in the center of the heme molecule by bonds to the four nitrogens of the porphyrin ring. • It can form two additional bonds, one on each side of the planar porphyrin ring. • - one of these positions is coordinated to a histidineof globin • - the other position is available to bind oxygen

  3. OXYGEN PORPHYRIN IX RING FERROUS ION HISTIDINE The heme group: Fe2+ porphyrin complex with bound O2

  4. Myoglobin • Location: • heart & skeletal muscles • Function: • a reservoir for oxygen for muscles. • an oxygen carrier that increases the rate of transport of oxygen • within the muscle cell. • Structure: • Myoglobin is composed of a single polypeptide chain that is structurally similar to the individual subunit polypeptide chain of hemoglobin. • ~ 80 % of its polypeptide chain is folded into 8 stretches of α-helix. These α-helical regions, labeled A to H

  5. Myoglobin cont. Globin Protein (Polypeptide Chain) The interior almost entirely of nonpolar amino acids. Polar amino acids are located almost exclusively on the surface of the molecule. Heme group is located in a pocket in the molecule between helix E and helix F which is lined by nonpolar amino acids with exceptions are two histidine amino acids.

  6. Myoglobin cont. • The first is called the proximal histidine (F8), binds directly to the iron of heme. • The second is called the distal histidine (E7), does not directly interact with the heme group, but helps stabilize the binding of oxygen to the ferrous iron. • The protein, or globin, portion of myoglobin prevents the oxidation of iron of heme.

  7. Myoglobin as a diagnostic tool • Myoglobin is used as a marker for acute myocardial infarction • Advantage: It is elevated in blood of patients with myocardial infarction than other markers as CK-MB or troponin. So, it can diagnose myocardial infarction attack at an early stage. • Disadvantage: myoglobin has a reduced specificity for diagnosing myocardial infarction.

  8. Hemoglobin • Location: • exclusively in red blood cells • Function: • main function is to transport oxygen, • H+ and CO2 • Structure: • Hemoglobin is composed of four polypeptide chains - two α chains and two β chains – arranged into 2 dimers held together by noncovalent interactions. • Each subunit has 8 stretches of α-helical structure, and a heme-binding pocket (as for myoglobin) • The oxygen-binding properties of hemoglobin are regulated by interaction with allosteric effectors

  9. Quaternary structure of hemoglobin • The hemoglobin tetramer can be envisioned as being composed of two identical dimers, (αβ)1 & (αβ)2(1 & 2 are numbers) • The two polypeptide chains within each dimer are held tightly together, primarily by hydrophobic interactions • In contrast, the two dimers are able to move with respect to each other, being held together primarily by polar bonds. • The weaker interactions between these mobile dimers result in the two dimers occupying different relative positions in deoxyhemoglobin as compared with oxyhemoglobin

  10. Quaternary structure of hemoglobin cont. TAUT Structure T RELAXED Structure R Structural changes resulting from oxygenation & deoxygenation of hemoglobin

  11. Quaternary structure of hemoglobin cont. • T form: • The two αβ dimers interact through a network of ionic bonds that constrain the movement of the polypeptide chains. • The T form is the low-oxygen-affinity form of hemoglobin. • R form: • The binding of oxygen to hemoglobin causes the rupture of some of the ionic bonds between the αβ dimers. • This leads to a structure called the “R,” or relaxed form, in which the polypeptide chains have more freedom of movement • The R form is the high- oxygen-affinity formof hemoglobin.

  12. Binding of oxygen to myoglobin & hemoglobin • Myoglobin can bind only one molecule of oxygen (O2), as it contains only one heme group. • Hemoglobin can bind four oxygen molecules (one at each of its four heme groups) • The degree of saturation (Y) of these oxygen-binding sites on all myoglobin or hemoglobin molecules can vary between zero (all sites are empty) and 100% (all sites are full

  13. Oxygen dissociation curve The oxygen dissociation curve is a plot of saturation of binding sites with O2 in hemoglobin or myoglobin (Y) measured at Different partial pressures of oxygen (pO2) ---------------------------------------------------------- Myoglobin has a higher oxygen affinity at any pO2 value than hemoglobin as: In myoglobin: pO2 needed to achieve 50% saturation of binding sites is ~ 1 mm Hg In hemoglobin: ~ 26 mmHg [The higher the O2 affinity (i.e. more tightly bound O2), the lower the pO2 needed]

  14. Allosteric effects • The ability of hemoglobin to reversibly bind oxygen is affected by: • pO2 • pH • pCO2 • 2,3-bisphosphoglycerate (2,3 DPG) • CO • These are collectively called allosteric (“other site”) effectors, because their interaction at one site on the hemoglobin molecule affects the binding of oxygen to heme groups at other locations on the molecule. • N.B.: The binding of oxygen to myoglobin is not influenced • by allosteric effectors.

  15. 1- pO2 (Oxygen Concentration) Loading & unloading of oxygen depend on pO2 (oxygen concentration 1- pO2 in alveoli of lungs (i.e. concentration of O2) is high So, affinity of HB to O2 is increased leading to saturation of hemoglobin with O2 (loading of oxgen) 2- pO2 in peripheral tissues is low So, affinity of HB to oxygen is decreased leading to release of oxygen to peripheral tissues (unloading of oxygen) AT THE SAME TIME: Myoglobin is designed to bind oxygen released from hemoglobin at low pO2 found in muscles (as myoglobin requires very low pO2 to be fully saturated with oxygen)

  16. 2- Bohr effect • Bohr effect is the change of oxygen binding in hemoglobin due to hydrogen ions (H+ or protons) and CO2 • In peripheral tissues, H+ & CO2 are increased, which results to increased release of oxygen from hemoglobin. • 1- H+released from metabolism of peripheral tissues • 2- CO2 resulting from cellular metabolism is converted by carbonic anhydrase to carbonic acid which is converted to bicarbonate & H+ • In both cases, H+ increases the ionic bonds favoring of T form of Hb O2 release to the tissues • Hb O2 (OxyHb, R form) + H+ ↔ HbH (deoxyHb, T form) + O2 • So, increase in H+ shift equilibrium to right

  17. CO2 • Most of CO2 produced during metabolism • Some CO2 is carried as carbamate bound to the uncharged amino group • Hg-NH2+ CO2 Hb-NH-COO- + H+ • This stabilizes the T –form

  18. 2,3-bisphosphoglycerate • Effect of 2,3-bisphosphoglycerate on oxygen affinity: • 2,3- Bisphosphoglycerate (2,3-BPG) is an important regulator of the binding of oxygen to hemoglobin. • 2,3-BPG is synthesized from an intermediate of the glycolysis. • Binding of 2,3-BPG to deoxyhemoglobin (T form): • 2,3-BPG decreases the oxygen affinity of hemoglobin by binding to deoxyhemoglobin but not to oxyhemoglobin. • This preferential binding stabilizes the T conformation of deoxyhemoglobin. • Response of 2,3-BPG levels to chronic hypoxia or anemia: • The concentration of 2,3-BPG in the red blood cell increases in response to chronic hypoxia (in certain lung diseases or high altitude) or chronic anemia • (oxygen available to Hb is low in both cases) • Elevated 2,3-BPG levels lower the oxygen affinity of hemoglobin, permitting greater unloading of oxygen in the capillaries of tissues.

  19. Binding of Carbon monoxide (CO) • Carbon monoxide (CO) binds tightly (but reversibly) to the hemoglobin iron, forming carboxyhemoglobin (carboxyHb) • Dangers of CO binding to hemoglobin (in CO poisoning) • 1- The affinity of hemoglobin for CO is 220 times greater than for oxygen (in availability of both, hemoglobin binds CO more) • 2- When carbon monoxide binds to one or more of the four heme sites, hemoglobin shifts to the relaxed conformation (R-form), causing the remaining heme sites to bind oxygen with high affinity (tightly). • As a result, the affected hemoglobin is unable to release oxygen to the tissues leading to tissue hypoxia. • CO poisoning is treated with 100% oxygen therapy to facilitate the dissociation of CO from hemoglobin.

  20. Factors favoring the T-form of Hb. are: • Deoxygenation • Low pH (  H+) • CO2 • Lactic acid • 2,3 bisphosphoglycerate • Factors favoring the R-form of Hb. are: • O2 • CO

More Related