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Haemoglobin

Role of Haem in Oxygen Binding


Haem is a prosthetic group that enables the oxygen-binding properties of each protein. Haem
groups have the capacity to bind Fe2+ which sits right in the middle of the haem porphyrin ring
stabilized by four N’s. The Fe2+ ion can make two more bonds that enable it to capture O2.
Haemoglobin has 4, whereas myoglobin only has 1.

Structure & Function of Myoglobin (Mb)


O2 reservoir within heart & skeletal muscle cells:
• 75% a- helix
• 8 helices (labelled A-H)
• Non-helical regions (AB, BC etc.)
• Exterior hydrophilic Schematic of O2 binding site
• Interior hydrophobic except histidines E7 (distal) & F8 (proximal)

Binding to O2 Proximal Histidine (F8)


Oxygenation: oxygen binds to the haem iron - bonded to haem Fe

which moves the proximal histidine F8 since


Distal Histidine (E7)
it is bound to the haem also. Helix F moves & - not bonded to haem
causes other elements of the structure to [steric role]
move.
Haem
plane

iant forms & &gene


Structure Functionexpression
of Haemoglobin (Hb)
Function – transport O2 and CO2.
Structure – four globin chains, each with one haem group therefore ability to bind four O2
molecules.

Hb type Expression Chains Gene Expression:


alpha chains (chromosome 16),
HbA Adult a 2b 2
beta chains (chromosome 11).
HbA 2 Minor adult form a 2d 2
HbF Foetal a 2g 2
Hb Gower 1 embryonic z 2e 2 O2 binding to Hb
Hb Gower 2 embryonic a 2e 2
• Sigmoid
• Cooperative
Hb Portland embryonic z 2g2

Hb vs. Mb
Hb vs. Mb: O2 binding

• Myoglobin has a higher affinity for O2 than haemoglobin


O2 binding
• Hb dissociates at a higher partial pressure than Mb.Hb vs. Mb
• This allows delivery of O2 from Hb to Mb.
• The oxygen-dissociation curve is steepest at the oxygen concentrations that occur in the tissues.
P 50 value:

This permits oxygen delivery to respond to small changes


The pOin2 at pO 2.%Small
which decrease
saturation = 50% in tissue pO2
leads to big decrease in Hb saturation.

• P50 value: The pO2 at which % saturation = 50% Mb: P50 = 1 Torr

HbA: P50 = 26 Torr

HbF: P50 = 20 Torr

1Torr = approximately 1mmHg

Allosteric Regulation
Mechanism of Cooperativity
Co-operativity:
• Binding of O2 to one haem group  affinity of remaining haem groups.
• Allows Hb to deliver 1.83x more O2 than if four sites were independent.
• Increase in affinity is due to Haem interactions
• Affinity of 4th O2 bound = 300x greater than 1st O2 bound.

Oxygenation:
• In deoxy-Hb (tense T-form) the subunits are constrained by eight salt-bridges (non-covalent
electrostatic interactions) – broken on oxygenation.
• the contact region is connected to the haem groups.
• movement at the haem group causes movement at the interface.
• The haem Fe moves further into plane
• The Fe pulls His-F8 towards the haem group
• Movement in the F helix, EF & FG corners
• Rupture of some salt bridges at the interface
• Hb becomes less constrained
Explain the effects of 2,3 BPG and the Bohr effect on Oxygen dissociation.

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