Oxygen Transport and Storage

Living systems use iron- and copper-based metalloproteins such as hemoglobin and myoglobin to bind oxygen reversibly, transporting it through the body and storing it in tissues.

Definition

Oxygen transport and storage is the bioinorganic chemistry by which metalloproteins bind molecular oxygen reversibly at a metal centre to carry it in the bloodstream and hold it in tissues for use in respiration.

Scope

This topic covers the bioinorganic chemistry of dioxygen carriers: the heme iron centres of hemoglobin and myoglobin, the cooperative oxygen binding of hemoglobin and its allosteric control, the structural changes that accompany oxygenation, and the alternative oxygen carriers hemocyanin and hemerythrin. It treats reversible oxygen binding and storage, leaving oxygen-activating catalysis to the metalloenzyme topic.

Core questions

• How does the heme iron centre bind oxygen reversibly without being oxidized?
• Why is hemoglobin's oxygen binding cooperative?
• What structural changes accompany oxygenation?
• How do hemocyanin and hemerythrin carry oxygen with copper or non-heme iron?

Key concepts

• Heme and the proximal histidine
• Reversible dioxygen binding
• Cooperativity and the sigmoidal curve
• Allosteric regulation
• Hemocyanin (dicopper)
• Hemerythrin (diiron)

Key theories

Reversible dioxygen binding at heme iron

The iron(II) centre of heme, held in a protein pocket with a proximal histidine, binds dioxygen end-on while the protein prevents irreversible oxidation, allowing repeated cycles of uptake and release.

Cooperativity and allostery in hemoglobin

Oxygen binding to one subunit triggers tertiary and quaternary structural changes that raise the affinity of the others, giving the sigmoidal binding curve that Perutz explained from the protein's stereochemistry.

Alternative oxygen carriers

Hemocyanin uses a dicopper site and hemerythrin a non-heme diiron site to bind dioxygen, showing that nature has evolved several distinct metal centres for reversible oxygen transport.

Mechanisms

In hemoglobin, oxygen binding to the iron of one subunit pulls the iron into the heme plane and shifts the attached histidine, propagating a quaternary change that converts the protein from a low-affinity to a high-affinity state and so makes binding cooperative.

Clinical relevance

The chemistry of oxygen carriers underlies respiratory physiology and disorders of oxygen delivery, the toxicity of carbon monoxide that competes for the heme site, and the molecular basis of conditions affecting hemoglobin; this is reference material, not clinical guidance.

History

The molecular basis of oxygen transport became clear with the first protein crystal structures: Kendrew solved myoglobin and Perutz solved hemoglobin, work recognized by the 1962 Nobel Prize. Perutz then explained cooperativity from the structural differences between the oxygenated and deoxygenated forms.

Key figures

• Max Perutz
• John Kendrew
• Linus Pauling

Seminal works

• perutz1970
• lippard1994
• bertini2007

Frequently asked questions

Why doesn't the iron in hemoglobin simply rust when it binds oxygen?

The protein pocket isolates each heme and positions a proximal histidine and distal residues so that oxygen binds reversibly without two iron centres meeting to form an irreversibly oxidized bridged species, keeping the iron available for repeated cycles.

What does cooperative binding accomplish physiologically?

Cooperativity gives hemoglobin a steep, sigmoidal oxygen-binding curve, so it loads oxygen efficiently where the partial pressure is high, in the lungs, and unloads it efficiently where the pressure is low, in the tissues.