Myoglobin And Haemolglobin

Question 1

Haem is a prosthetic group that binds oxygen

Answer 1

Oxygen is poorly soluble, so animals have evolved carrier molecules

Iron (Fe) readily binds oxygen, but free iron is toxic
Fe is bound to the prosthetic group haem, which contains a porphyrin ring

Coordinate Bonds are formed between Fe and the nitrogen atoms of the porphyrin ring

Haem bound to oxygen has a different structure than when not bound

Question 2

Myoglobin is a haem-containing muscle protien

Answer 2

Myoglobin (Mb) is monomeric and is involved in oxygen diffusion to muscle tissues

Diving mammals like seals store a lot of oxygen in myoglobin

Myoglobin has a single polypeptide chain of 153 amino acids and one molecule of haem
The haem binds to 2 specific histidine residues

Haemoglobin - lungs- tissue
Myoglobin - in muscles

Question 3

Haemoglobin transports oxygen through blood

Answer 3

Hb is a tetramer with a 2 a chain of 141 residues and 2 b chains of 146 residues

Each monomer is structurally similar to myoglobin even through the amino acids sequence is very different

The quaternary structure of haemoglobin features strong interactions between unlike subunits
— the a1b1 interface (and its a2b2 counterpart) involves more than 30 residues
—the a1b2 (and a2b1) interface involves 19 residues

Important interactions include the hydrophobic effect, hydrogen bonds and the electrostatic interactions .

Question 4

Haemoglobin has high -affinity and lower- affinity states

Answer 4

Tense = Lowe affinity state, the lower partial pressure

Relaxed = high affinity state, high partial pressure

Question 5

Haemoglobin binds oxygen cooperatively

Answer 5

The more molecules of O2 that haemoglobin binds, the higher affinity for O2 becomes
A single molecules of Hb can bind a max of 4 O2 molecules
One per subunit

Question 6

Why does haemoglobin bind oxygen cooperatively

Answer 6

Haemoglobin must bind oxygen efficiently in the lungs, where the pO2 (partial pressure of oxygen) is about 13.3 kPa, and release oxygen in the tissues, where the pO2 is about 4 kPa.

A high-affinity conformation would bind O2 effectively in the lungs but not readily release it in tissues (and vice-versa).

Haemoglobin transitions from low to high affinity states as
more oxygen molecules are bound.

In an allosteric protein the binding of a ligand to one site affects the binding properties of another site on the same protein.

NB: Carbon monoxide (CO) binds haem 250 times more readily than O2, which is why it is so dangerous.

Question 7

Haemoglobin also binds H+ and CO2

Answer 7

H+ and CO2 are two by products of cellular respiration and are carried to the kidneys and lungs for excretion

The enzyme carbonic a hydrate catalyse the hydration of CO2 to bicarbonate (which iOS more soluble than CO2
CO2 + H2O ⇌ H+ + HCO3-
Recall that increasing [H+] decreases pH

The binding of H+ and CO2 is inversely related to the binding of oxygen this is known as the Bohr effect
— in tissues there is a relatively high [H+] and [CO2] so haemoglobins affinity for O2 is relatively low

—In lung capillaries [H+] and [CO2] are low, so haemoglobin’s O2 affinity is high.

Question 8

CO2 binds the amino terminus of globin subunits

Answer 8

Carbon dioxide binds to the amino group at the N-terminus of each globin chain, forming carbaminohaemoglobin.

This introduces a new negative charge, stabilising the low O2-affinity state of haemoglobin and promotes the release of O2.

Question 9

2,3-bisphosphoglycerate regulates O2 binding to haemoglobin

Answer 9

BPG decreases the O2 affinity of haemoglobin, and is relatively abundant in red blood cells.
One molecule of BPG binds one molecule of haemoglobin at the cavity between the β subunits, and stabilises the low O2 affinity state.
BPG plays a key role in adapting to low pO2 conditions, such as high altitudes:
• At high altitude [BPG] increases, lowering O2
affinity of haemoglobin so more is transferred to tissues.

Question 10

List four “tricks” haemoglobin uses to make it a more efficient oxygen carrier in the blood.

Answer 10

1. Hb binds O2 cooperatively: the more oxygen Hb binds the easier it is to bind more
2. The Bohr effect: When Hb binds H+ (happens when blood pH decreases) oxygen affinity decreases
3. Hb + CO2 → Carbaminohaemoglobin. Extra negative charge stabilises the low oxygen affinity state
4. Red blood cells produce BPG: Higher [BPG] means lower oxygen affinity