Bioinorganic Chemistry

Bioinorganic ChemistryHemoglobin and MyoglobinOxygen transfer and storage agents in the blood and muscle tissue.Hemoglobin transports oxygen (O2) from the lungs/gills to tissues and muscles.Myoglobin stores oxygen (O2) in the muscles and tissues.Oxygen commonly transfers from the hemoglobin to the myoglobin for later use.CooperativityThe function of hemoglobin is to bind O2 at high oxygen pressure and carry it through the blood to needed areas (and myoglobin for storage).Hb + 4O2 Hb(O2)4Hb(O2)4 + 4Mb 4Mb(O2) + HbAs one iron binds an oxygen molecule in Hb, the molecular shape changes to make binding of additional oxygen molecules easier. In a similar fashion, initial removal of oxygen triggers the release of the remaining oxygens.Hemoglobin: cooperativityHemoglobin: cooperativity

Cooperative binding of oxygen by the four subunits of hemoglobin means that the binding of an oxygen molecule at one heme group increases the oxygen affinity of the remaining heme groups in the same hemoglobin molecule

5The cooperative binding of oxygen allows hemoglobin to deliver more oxygen to the tissues in response to relatively small changes in the partial pressure of oxygen.

In the lung, the concentration of oxygen is high and hemoglobin becomes saturated (or loaded) with oxygen. In the peripheral tissues, oxyhemoglobin releases (orunloads) much of its oxygen for use in the tissues 6

Saturation curve for Mb shows rapid oxygen concentration-dependent saturation of monomeric oxygen-binding protein.

The Hb curve shows the sigmoidal saturation curves for cooperative oxygen binding.

Also indicated in the diagram are the typical oxygen concentrations in peripheral tissues and the lungs.

Note that whereas, myoglobin can be fully oxygen saturated in the tissues, hemoglobin requires much higher oxygen concentration to become fully saturated which only occurs in the lungs.At low partial pressures of O2, Mb has a much greater affinity for O2.

It is essential that Hb's saturation curve for O2 binding be sigmoidal, rather than hyperbolic. In this case, Hb is saturated at pO2 found in the lungs, but binds O2 weakly at pO2 found in the tissues. This is possible due to cooperativity. The binding of O2 at one site in Hb increases the affinity for O2 at other sites in the same Hb molecule. Bohr effect

8The release of oxygen from hemoglobin is enhanced when the pH is lowered or when the hemoglobin is in the presence of an increased partial pressure of CO2. This result in a decreased oxygen affinity of hemoglobin and a shift to the right in the oxygen dissociation curve.This change in oxygen binding is called the Bohr effect. Conversely, raising the pH or lowering the concentration of CO2 results in a greater affinity for oxygen, and a shift to the left in the oxygen dissociation curve.The Bohr effectDuring respiration, CO2 is produced. This diffuses into the blood plasma and into the red blood cells.

Inside the red blood cells are many molecules of an enzyme called carbonic anhydrase *. It catalyses the reaction between CO2 and H2O.

CO2+H2OH2CO3The resulting carbonic acid then dissociates into HCO3- + H+.(Both reactions are reversible).Red cellplasmaCO2H2CO3HCO3- + H+.*H2OHCO3-The binding power of Hb with oxygen is pH dependent --- Bohr effectHaemoglobin very readily combines with hydrogen ions forming haemoglobinic acid. As a consequence haemoglobin releases some of the oxygen it is carrying.By removing hydrogen ions from the solution, haemoglobin helps to maintain the pH of the blood close to neutral. It is acting as a buffer.

Hemoglobin binds H+ when it releases O2HbO2 + H+ HbH+ + O2At the lungs, when oxygen rebinds, the H+ released is converted to carbon dioxide and exhaled. About 40% of acid produced by the tissues is buffered in this way by HbThe Bohr effect

Three Oxygen Dissociation curves illustrating the Bohr Effect. Increased carbon dioxide in the blood causes a right-shift in the curves, such that the haemoglobin more easily unloads the oxygen it is carrying.

Na+-K+ PumpThe sodium-potassium pump actively maintains the gradient of sodium (Na+) and potassium ions (K+) across the membrane.Typically, an animal cell has higher concentrations of K+ and lower concentrations of Na+ inside the cell.uses the energy of one ATP to pump three Na+ ions out and two K+ ions in.

Cytoplasmic Na+ bonds tothe sodium-potassium pumpCYTOPLASMNa+[Na+] low[K+] highNa+Na+EXTRACELLULARFLUID[Na+] high[K+] lowNa+Na+Na+ATPADPP Na+ binding stimulatesphosphorylation by ATP.Na+Na+Na+K+ Phosphorylation causesthe protein to change itsconformation, expelling Na+to the outside.P Extracellular K+ bindsto the protein, triggeringrelease of the phosphategroup.PP Loss of the phosphaterestores the proteinsoriginal conformation. K+ is released and Na+sites are receptive again;the cycle repeats.K+K+K+K+K+