2. oxygen transport-haemoglobin and myoglobin

8/2/2019 2. Oxygen Transport-Haemoglobin and Myoglobin

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Proteins and their Relation to life


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Myoglobin, Hemoglobin, Cytochromes bind O2

-

Oxygen is transported from lungs to various tissues via blood inassociation with hemoglobin

In muscle, hemoglobin gives up O2 to myoglobin which has a higher

affinity for O2 than hemoglobin.xygen- n ng curve or emog o n s s gmo a w ereas or

myoglobin it is hyperbolic.

.Cytochromes participate is redox reactions and are components of

.


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Hemoglobin Structure

Hemoglobin is a O 2 transport protein found in the RBCs

An oligomeric protein made up of 2 dimers, a total of 4

polypeptide chains: 1122.

Molecular weight : 64,500.

e aa an aa su un s ave en y.

The 3D- structures of (141 aa) and (146 aa) subunits of

similar; all three are members of the globin family.

Each Hb subunit consists of 7 or 8 al ha helices and

several bends and loops folded into a single globin domain.

Each subunit has a heme-binding pocket.


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The Prosthetic Heme GrouThe heme group is responsible for the O 2-binding capacity of

hemoglobin.

The heme group consists of the planar aromatic protoporphyrin made upof four pyrrole rings linked by methane bridges.

A Fe atom in its ferrous state (Fe +2) is at the center of protoporphyrin.

Fe+2 has 6 coordination bonds, four bonded to the 4 pyrrole N atoms.The nucleophilic N prevent oxidation of Fe +2.

The two additional binding sites are one on either side of the heme plane.

One of these is occupied by the imidazole group of His.The second site can be reversibly occupied by O 2, which is hydrogen

on e to anot er s.


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When hemoglobin is bound to O 2, it is called oxyhemoglobin .

This is the relaxed (R ) state.The form with a vacant O 2 binding site is called deoxyhemoglobin and

corresponds to the tense (T) state.

If iron is in the oxidized state as Fe+3

, it is unable to bind O 2 and this formis called as methemoglobin

CO and NO have higher affinity for heme Fe +2 than O 2 and can displace

2 rom , accoun ng or e r ox c y.


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Hemoglobin exists in two major conformational states:

an s a es o emog o n

Relaxed (R ) and Tense (T)R state has a higher affinity for O2.

In the absence of O2, T state is more stable

When O2 binds, R state is more stable, so hemoglobinundergoes a conformational change to the R state.

The structural change involves readjustment of interactions

between subunits.


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Changes Induced by O2 Binding

O2 binding rearranges electrons within Fe+2 making it more

compact so that it fits snugly within the plane of porphyrin.

Since Fe is bound to histidine of the globin domain, when Femoves, the entire subunit undergoes a conformational change.

This causes hemoglobin to transition from the tense (T) state

to the relaxed (R) state.The 11 and 22 dimers rearrange and rotate approximately

15 degrees with respect to each other

Inter-subunit interactions influence O2 binding to all 4 subunitsresulting in cooperativity.


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O2-binding kinetics

,O2 binding is cooperative meaning that each subsequent O2

binds with a higher affinity than the previous one

Similarly, when one O2 is dissociated, the other three willdissociate at a sequentially faster rate.

Due to positive cooperativity, a single molecule is very rarely

partially oxygenated.There is always a combination of oxygenated and deoxygenated

hemoglobin molecules.

The percentage of hemoglobin molecules that remain oxygenated isrepresented by its oxygen saturation.

- n ng curves s ow emog o n saturat on as a unct on o t e

partial pressure for O2.


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Myoglobin - Structure

A simple oxygen-binding protein found in almost all mammals, primarily in

muscle tissue.

Myoglobin ( Mr 16,700; abbreviated Mb)

As a transport protein, it facilitates oxygen diffusion in muscle.

Myoglobin is abundant in the muscles of diving mammals such as

seals and whales

so as oxygens orage unc on or pro onge excurs ons un ersea.

A single polypeptide of 153 amino acid residues with one molecule of heme.

,

similar primary and tertiary structures.

The ol e tide is made u of ei ht -helical se ments 78% connected b

bends.


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LUNGS MUSCLE CELLO2+ 4e

- + 4H+

2H2O

RED BLOOD CELL

O2deoxyMbMbO2

eoxy

pO2 = ~20-30 torr

p 2= orr

O2 O2Hb(O2)n Hb(O2)n

1.0HyperbolicY

K diss (half-saturation)

.

pO2

2. oxygen transport-haemoglobin and myoglobin

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