Oxygen Binding Proteins

Myoglobin

Binds oxygen and stores it for use when muscles expend energy and need to convert molecules from food into useable forms

Heme

The prosthetic group of myoglobin and haemoglobin and consists of an organic constituent, protoporphyrin IX, and an iron atom

Myoglobin binding O2

Myoglobin binds O2 as the O2 partial pressure increases

Oxygen binding curve

Plots the fraction of possible binding sites that contain O2 , the curve rises as O2 partial pressure increases then levels off

Structure of myoglobin

a single polypeptide chain, made up of alpha-helixes, and a heme ligand

Structure of Heme

Organic compound, made of four linked pyrrole rings attached with a central iron atom by nitrogen and its binding sites are referred to as the 5th and 6th coordination sites

Deoxymyoglobin

Oxygen-free myoglobin

Structure of Deoxymyoglobin

The iron is in a ferrous oxidation state and is too large to fit in porphyrin ring. The sixth site unoccupied

Oxymyoglobin

Bound oxygen myoglobin

Structure Oxymyoglobin

Forms when oxygen binding occurs in the 6th coordination site and rearranges the electrons within the iron so that the ion becomes smaller, allowing it to move into the plane of the porphyrin

Myoglobin and Carbon Monoxide

CO blocks and inactivates the binding site of myoglobin, preventing the binding of O2

Haemoglobin

Heme-containing oxygen carrier found in the bloodstream

Structure of Haemoglobin

Four polypeptide chains, two alpha-helices and two beta-sheets

Haemoglobin binding

O2 binding for haemoglobin is weaker than for myoglobin

Cooperative binding behaviour

Binding reactions of individual sites are not independent

Haemoglobin oxygen binding curve

Sigmoidal curve indicates that the binding site of oxygen at one site within haemoglobin increases likelihood of O2 binding at the remaining unoccupied sites

Advantages of cooperative binding behavior

Efficient O2 transport, release of O2 favours more complete delivery to tissue, O2 delivered to tissue where needed most

Oxygen binding in Haemoglobin

Alpha1,Beta1 dimers in quaternary structure rotate 15 degrees with respect to one another, the interface between Alpha1,Beta1 and Alpha2,Beta2 dimers affected as free to move with respect to one another in oxygenated state

T state

Quaternary structure in deoxy form of haemoglobin (tense)

R state

Quaternary structure of oxy form of haemoglobin (relaxed)

2,3 Bisphosphoglycerate

In the presence of 2,3-BPG, haemoglobin can transition from a high-oxygen-affinity state to a low-oxygen-affinity state, making oxygen transport more efficient

How does 2,3-BPG work

Single molecule of 2,3-BPG binds in a pocket in the centre of the tetramer of haemoglobin (only present in T-state), During T-state to R-state transition the pocket collapses, releasing 2,3-BPG. Therefore in order for the structural transition from T to R, the interactions between 2,3-BPG and haemoglobin must be disrupted. In the presence of 2,3-BPG, more O2 binding sites within haemoglobin tetramer must be occupied for the T-to-R transition and so haemoglobin remains in lower-affinity T-state until higher O2 concentrations are reached

Affect of Hydrogen and Carbon Dioxide in O2 release

Haemoglobin responds to higher levels of hydrogen and carbon dioxide in tissues and will release O2 to where it is needed most

Hydrogen ions

O2 affinity of haemoglobin decreased as pH decreases from value of 7.4, ionic interactions stabilise T-state leading to a greater tendency to release O2

Carbon Dioxide effect

CO2 reacts with water to form bicarbonate ion (H3O+ and H+), dropping the pH that stabilises T-state

Sickle Cell Anemia

Abnormal sickle shape of red blood cells deprived of oxygen

How sickle cell anaemia works

Haemoglobin molecules form large fibrous aggregates which extend across the red blood cell, distorting them so they clog small capillaries and impair blood flow. They don’t remain in circulation for long as when sickling occurs, can increase tendency of cells to lyse, leading to anaemia