8/13/2019 HIS 6 - Haemoglobin

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HIS 6 - Haemoglobin

Recall oxygen binding properties of Hb

HbA has 4 subunits α2β2 Each protein subunit contains a haem prosthetic group

iron(II)- protoporphyrin IX A prosthetic group is tightly bound to a protein and required

for protein activity

Recall general properties of haemoglobin and myoglobin.

4 subunits each myoglobin like 2 and 2 globin chains (salt bridge

interactions) Primary - different from myoglobin Secondary/Tertiary - same as myoglobin Quarternary - Myoglobin has no quarternary

Compact shape with globin chain foldedabout the haem group

Globin chain in structure has 8 major(non)/helical regions

Interior hydrophobic (Haem group) Exterior hydrophilic Haem group linked to globin chain

through the proximal histidine .

Describe allosteric regulation of haemoglobin. Haemoglobin is an allosteric protein. An allosteric protein in one in which an

interaction at one site in the molecule affects interactions at remote sites.1. O2 binding at one site assists with binding of O2 in other sites.2. Binding of CO 2 and H + at certain sites result in charged groups being

formed, results in formation of salt linkages , squeezing O2 molecules fromother sites. It enhances release of O2 in metabolically active tissue suchwhere much CO 2 and H

+ is produced and where much oxygen is required.3. Binding of O2 to haemoglobin in alveolar capillaries of lungs causes breaking

of salt linkages and release of CO 2 and H+ in non-adjacent sites.

Myoglobin is not an allosteric protein.

Haemoglobin Myoglobin Present in RBC and responsible for O 2

transport.

Contains 65% of the iron in the body. Anaemia - A lack of haemoglobin.

Present in muscles, stores O 2 andtransports across muscle cells.

Contains 6% of iron in the body.

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Define ‘cooperative oxygen binding’.

Hemoglobin is a compact structure in which the globin chains interact by salt linkages Hemoglobin molecule said to be in a T state (tense or taut) Addition of the 1st oxygen molecule in haemoglobin is difficult

o When oxygen binds, Fe(II) goes from high-spin to low-spino Proximal histadine attached to iron moves with ito Globin chain attached to histadine also moves with ito Ultimately causing the salt links to break and it opens up and relaxes -R stateo Cooperative oxygen binding - Other haem groups become exposed and the

second, third and fourth oxygen molecules add easily.

Explain the effects of 2,3 BPG on oxygen disassociation

2,3-BPG binding releases oxygens present on haemoglobin. 2,3-BPG lowers haemoglobin's binding affinity for oxygen allowing the detached

oxygen atoms to travel to tissues requiring oxygen .

Explain the effects of ‘Bohr Effect’ on oxygen disassociation The inter-relationship between H +, CO 2 and O 2 binding In haemoglobin is called the

Bohr Effect. Shifts the curve to the right An effect by which an increase of carbon dioxide in the blood and a decrease in pH

results in a reduction of the affinity of hemoglobin for oxygen At a lower pH, a greater pO2 is required to achieve any given oxygen saturation.