Haemoglobin and Myoglobin

name the 2 oxygen proeins
1xstroage
1x transport

hemoglobin

myoglobin

which is more efficent myoglobin or hemoglobin

hemoglobin is a remarkably efficient oxygen carrier, able to use as much as 90% of its potential oxygen-carrying capacity effectively. Under similar conditions, myoglobin would be able to use only 7% of its potential capacity.

why is hemoglobin more efficent than myoglobin from a structural point of view

Myoglobin exists as a single polypeptide, whereas hemoglobin comprises four polypeptide chains.

how do the 4 chains in hemoglobin bind oxygen

cooperatively,

what does cooperative binding mean

hat the binding of oxygen to a site in one chain increases the likelihood that the remaining chains will bind oxygen.

name the 2forms that myoglobin can exist in

deoxymyoglobin or in a form with an oxygen molecule bound called oxymyoglobin

what does the ability of myoglobin to bind to oxygen depnd on

The ability of myoglobin and hemoglobin to bind oxygen depends on the presence of a heme molecule.

what components does heme consist of

t consists of an organic component and a central iron atom.

organic component of heme

protoporphyrin, is made up of four pyrrole rings linked by methine bridges to form a tetrapyrrole ring.

what is attached to the central tetrapyrrole ring of heme

Four methyl groups, two vinyl groups, and two propionate side chains are attached to the central tetrapyrrole.

where does the iron atom lie in the heme structure

The iron atom lies in the center of the protoporphyrin, bonded to the four pyrrole nitrogen atoms.

which state of iron bonded to heme allows for the binding to oxygen

only the Fe 2+ state is capable of binding oxygen.

what are the the fifth and sixth coordination sites in heme

The iron ion can form two additional bonds, one on each side of the heme plane.

in myoglobin what is the 5th coordination site

In myoglobin, the fifth coordination site is occupied by the imidazole ring of a histidine residue from the protein.

what is the 5th coordination site of myoglobin referred to as

proximal histidine.

where does oxygen binding occur in the myoglobin molecule

Oxygen binding occurs at the sixth coordination site.

In deoxymyoglobin, this site remains unoccupied.

what is Oxygen binding to iron in heme accompanied by

partial transfer of an electron from the ferrous ion to oxygen.

what does the binding part of myoglobin include

the binding pocket of myoglobin includes an additional histidine residue (termed the distal histidine )

what does the distal histidine do

donates a hydrogen bond to the bound oxygen molecule

what does the protein component of myoglobin control

-intrinsic reactivity of heme
-makes it more suitable to bind to oxygen reversibly

what is human hemoglobin an assembly of

an assembly of four myoglobin-like subunits

how many chains and what type of structures does hemoglobin consisit of

Hemoglobin consists of four polypeptide chains, two identical a chains and two identical /3 chains

explain the structure of the pairing of alpha and beta strands in hemoglobin

one alpha stand and one beta strand interacts due to preferential ionic pairs

explain the formation of the hemoglobin tetramer,

referred to as hemoglobin A (HbA), is best described as a pair of identical alpha beta dimers that associate to form the tetramer.

what shape of a binding curve is noticed when myoglobin binds

a binding curve indicating a simple chemical equilibrium is observed

what shape of an oxygen binding curve is noticed with hemoglobin

a sigmoidal shape

what does a sigmoid binding curve suggest

A sigmoid binding curve indicates that a protein exhibits a special binding behavior.

graph of binding and hemoglobin explained

For hemoglobin, this shape suggests that the binding of oxygen at one site within the hemoglobin tetramer increases the likelihood that oxygen binds at the remaining unoccupied sites.

graph of unbinding and hemoglobin explained

the unloading of oxygen at one heme facilitates the unloading of oxygen at the others.

what is the term given to the binding of oxygen to hemoglobin

cooperative, because the binding reactions at individual sites in each hemoglobin molecule are not independent of one another.

what does the cooperative binding of oxygen require

he binding of oxygen at one site in the hemoglobin tetramer influence the oxygen binding properties at the other sites.

what happens to hemoglobin when oxygen binds

undergoes substantial changes in quaternary structure on oxygen binding:

explain uthe substantial changes in quaternary structure when oxygen binds to hemoglobin

the alpha one and beta one and athe alpha 2 beta 2dimers rotate approximately 15 degrees with respect to one another

this leads to localised conformational changes

what is most affected by the binding of oxygen and hemoglobin and what does this allow for

the interface between the alpha one beta one and the alpha two beta two dimers is most affected

this means that they are easier to move

what is the quaternery structure of deoxyhemoglobin referd to as and why

T (for tense) state

it is quite constrained by subunit-subunit interactions.

what is the quaternery structure of oxyhemoglobin refered to as and why

R (for relaxed) state.

the oxygen-binding sites are free of strain and are capable of binding oxygen with higher affinity than are the sites in the T state.

what is achieved by triggering the shift of the hemoglobin tetramer from the T state to the R state,

the binding of oxygen to one site increases the binding affinity of other sites.

name the 2 models that were used to explain the cooperative process and the equilibrium between the T and the r state

concerted model

sequential model

explain the concerted model

explain the sequential model

The binding of oxygen changes the conformation of the subunit to which it binds.

This conformational change induces changes in neighboring subunits that increase their affinity for oxygen

why can you not use myoglobin to transport oxygen

myoglobin binds oxygen too tightly to be useful in oxygen transport.

What must occur or hemoglobin to funtion properly

he T state must remain stable until the binding of sufficient oxygen has converted it into the R state.

is the t state of hemoglobin stable

no
-highly unstable

what is used in human rbc to stabilise the t-state

2,3-BPG

what would occur if there was not 2,3 BPG in rbc

the affinity of hemoglobin to oxygen would be too high andd asa result the hemoglobin would not release oxygen

where is 2,3 BPG present in the deoxyhemoglobin

a single molecule of 2,3-BPG binds in the center of the tetramer, in a pocket present only in the T form

what happens to the pocket in which 2,3 BPG is located when a transition from t-r occurs

T-to-R transition, the pocket collapses and 2,3-BPG is released

what must occur for the transition of t-r in relation to 2,3 BPG

the bonds between hemoglobin and 2,3-BPG must be broken

how does 2,3 BPR lower the affinity of hemogllobin for oxygen

In the presence of 2,3BPG, more oxygen-binding sites within the hemoglobin tetramer must be occupied in order to induce the T-to-R transition,

hemoglobin remains in the lower -affinity T state until higher oxygen concentrations are reached.

name a substance which can disrupt o2 transport by hemoglobin

carbon monoxide

what is carbon monoxide

s a colorless, odorless gas

what is carboxyhemoglobin

when carbon monoxide binds to the same site that oxygen binmds it forms this complex

why is carbon mponoxide and the formation of the carboxyhemoglobin so bad

irst, carbon monoxide binds to hemoglobin about 200-fold more tightly than does oxygen.
Even at low partial pressures in the blood, carbon monoxide will displace oxygen from hemoglobin, preventing its delivery.

Second, carbon monoxide bound to one site in hemoglobin will shift the oxygen saturation curve of the remaining sites to the left, forcing the tetramer into the R state. This results in an increased affinity for oxygen, preventing its dissociation at tissues.

other than 2,3 BPG what can cause the release of oxygen

h+ and co2

what is the collective name given to 2,3BPG H+ and CO2

allosteric effectors

what happens to the affinity of hemoglobin when placed in a low pH

The oxygen affinity of hemoglobin decreases

the tendency of the hemoglobin to realse oxygen increases as the pH decreases

what is a disease associated with hemoglobin

sickle cell anemia

what causes sickle cell anemia

a single amino acid substitution in the beta chain of hemoglobin is responsible

the replacement of a glutamate residue with valine in position 6.

what is the mutated form of hemoglobin refered to as

The mutated form is referred to as hemoglobin S (HbS).

what must you have to get sickle cell anemia

both alleles of the hemoglobin (5-chain gene (HbB) are mutated.

i.e you have 2 of the HbS genes

in the HbS gene where does the new valine lie

new valine residue lies on the surface of the T-state molecule

how do aggregates form of the sickle cell gene

valin makes it hydrophobic patch

this new hydrophibic patch interacts with another patch which is formed by Phe 85 and Leu 88 of another neighbouring beta chain

this causes aggregation

what is significant about sickle cell anemia and africa

-sickle cell anemia is very common in africa

-people with sickle-cell trait exhibit enhanced resistance to malaria,

the parasite that causes malria llives within red blood cells at one stage in its life cycle.

if the red blood cells are unhealthy the parasite cannot survive and as a result the person will not die of malaria