9477 / 2027

Lesson 6 of 7 / Biological molecules

Haemoglobin: a globular protein that carries oxygen

Why does haemoglobin dissolve, and how does it pick up and drop off oxygen?

I can describe the molecular structure of haemoglobin and relate it to oxygen transport.

  • I can explain protein structural levels and stabilising interactions.Syllabus

    Syllabus 9477, Core 1(m). Explain protein structural levels and stabilising interactions.

  • I can relate haemoglobin and collagen structures to function.Syllabus

    Syllabus 9477, Core 1(o). Relate haemoglobin and collagen structures to function.

About 7 min

Make a guess. You are not marked.

Haemoglobin is a large protein, yet it dissolves in the cytoplasm of a red blood cell. Why?

  1. Hydrophilic R groups face outwards towards water.
  2. It does not dissolve; it floats as solid crystals.
  3. Its iron ions make it dissolve.
Show the answer

Hydrophilic R groups face outwards towards water.

Folding puts hydrophobic R groups inside and hydrophilic ones on the surface, where they hydrogen bond with water.

The key idea

Haemoglobin is four folded chains, each holding a haem group whose Fe2+ binds one oxygen molecule reversibly. Hydrophilic R groups on the outside make it soluble.

Structure for a function

Compare a globular transporter with a fibre

Explore the idea

Binding sites and their occupancy

alphaFebetaFealphaFebetaFe

0 sites occupied; the molecule still has four subunits and four haem groups. Oxygen binds at the iron in each haem group and can later be released.

The orange site includes iron even when its label shows O2. This model demonstrates capacity and occupancy, not a quantitative oxygen-dissociation curve.

Explanation

Haemoglobin carries oxygen inside red blood cells. It is a globular protein: its chains fold into a compact, roughly spherical shape. It has quaternary structure, because it is made of four polypeptide chains (subunits): two alpha-globin chains and two beta-globin chains. Each chain is folded into its own tertiary structure, and the four fit tightly together.

Haemoglobin dissolves in water, and the reason is the way each chain folds. Amino acids with hydrophobic R groups point inwards, into the centre of the molecule. Amino acids with hydrophilic R groups face outwards. These outer R groups form hydrogen bonds with water, so the molecule is soluble. A red blood cell can therefore hold a very large amount of haemoglobin dissolved in its cytoplasm.

Each of the four chains holds one haem group. Haem is a non-protein part (a prosthetic group) with an iron(II) ion, Fe2+, at its centre. Each Fe2+ binds one O2 molecule, and the binding is reversible. One haemoglobin molecule can therefore carry up to four O2 molecules. Each haem sits in a hydrophobic pocket of its chain, which helps keep the iron as Fe2+. Iron that has been oxidised to Fe3+ cannot bind oxygen.

The four subunits work together. When one O2 binds, that subunit changes shape slightly. Because the subunits are held together, the change spreads to the others and raises their affinity for oxygen. This is cooperative binding: each oxygen that binds makes the next one easier to load. In the lungs, where there is a lot of oxygen, haemoglobin quickly becomes nearly full. In respiring tissues, where there is less oxygen, it releases oxygen.

To answer a structure-function question, name the feature, state what it does, then link it to the job. For example: hydrophilic R groups face outwards, so haemoglobin forms hydrogen bonds with water and is soluble, so it can be packed into red blood cells to transport oxygen. Saying only that haemoglobin carries oxygen gives no mechanism and scores little.

Step by step
  1. 1

    Name the feature

    For example: four subunits, haem with Fe2+, or hydrophilic R groups on the outside.

  2. 2

    Say what it does

    Binds O2 reversibly, passes a shape change between subunits, or forms hydrogen bonds with water.

  3. 3

    Link it to the job

    Carries up to four O2, loads in the lungs and unloads in tissues, or dissolves in red blood cells.

Worked example

Work through the evidence

In one inherited form of haemoglobin, a hydrophilic amino acid on the outside of each beta chain is replaced by a hydrophobic one. Predict how this affects the molecule.

One way to explain it

The outer surface now has a hydrophobic patch. These patches make the molecules less soluble and make them stick to each other, especially when they are carrying little oxygen. The haemoglobin can clump into long fibres that distort the red blood cell. This is what happens in sickle-cell anaemia.

Why this answer works
  • Find which feature has changed: an R group on the outer surface.
  • Link the hydrophobic R group to lower solubility and molecules sticking together.
  • Link clumped haemoglobin to a change in red blood cell shape.

Watch out for this

A student says: "Oxygen binds to the polypeptide chains of haemoglobin." What is wrong with this?

Show the answer

Oxygen binds to the Fe2+ ion in each haem group. The polypeptide chains hold the haem in place and pass the shape change between subunits.

Check your understanding

Why is haemoglobin soluble in water?

  1. Its haem groups contain iron ions, which carry a charge and so attract water.
  2. Its four chains are held together by covalent cross-links.
  3. Hydrophilic R groups on its outer surface form hydrogen bonds with water.
Show the answer

Hydrophilic R groups on its outer surface form hydrogen bonds with water.

Hydrophobic R groups point inwards and hydrophilic R groups face outwards, so the molecule dissolves.

Quick recall

Card 1 of 3. Answer in your head, then check.

Why does haemoglobin dissolve, and how does it pick up and drop off oxygen?

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