Self-association, cooperativity and supercooperativity of oxygen binding by hemoglobins.
Cooperative ligand binding by tetrameric vertebrate hemoglobins (Hbs) makes possible the delivery of oxygen at higher pressures than would otherwise occur. This cooperativity depends on changes in dimer-dimer interactions within the tetramer and is reflected in a 50 000-fold increase in the tetramer-dimer dissociation constant in human Hb upon oxygenation at pH 7.4, from approximately 2x10(-11)mol l-1 to approximately 10(-6)mol l-1. Hbs that undergo such ligand-dependent changes in association are widespread in non-vertebrates, where the mechanisms are very different from those in vertebrates. Oligomeric Hbs have been identified in organisms in five phyla (molluscs, echinoderms, annelids, phoronids and chordates) that dissociate to subunits upon oxidation of the heme iron and reassociate with the binding of ferric iron ligands such as CN-, N3- or NO2-. Thus, the valence and ligand state of the heme iron control the stability of a critical subunit interface. The broad distribution of this phenomenon suggests a common mechanism of communication between heme and interface that may be almost universal among non-vertebrate Hbs. This interaction may be similar to that known for the homodimeric Hb of the mollusc Scapharca inaequivalvis. Although muscle tissue Hbs or myoglobins (Mbs) are usually monomeric, with non-cooperative O2 binding, the radular muscles of gastropod molluscs and chitons have homodimeric Mbs that bind O2 cooperatively. Cooperative non-muscle tissue Hbs have also been identified. These include the neural Hb of the nemertean worm Cerebratulus lacteus and the Hb of the diving beetle Anisops assimilis, which exhibit deoxygenation-dependent self-association of monomers that is associated with high Hill coefficients. Calculations suggest that the 2-3 mmol l-1 concentration of Hb on a heme basis in the brain of Cerebratulus should substantially extend the time as an active predator in an anaerobic or hypoxic environment. Oxygen from the Hb of Anisops is delivered to a gas bubble and thereby controls the buoyant density. Many Hbs of amphibians, reptiles, birds and some embryonic mammals exhibit a further 'supercooperativity' of O2 binding which depends on reversible deoxygenation-dependent tetramer-tetramer association to form an assemblage with a very low affinity for O2. This phenomenon results in steeper O2-binding curves than exhibited by tetramers alone. The increased cooperativity should result in an increase in the amount of O2 delivered to the tissues and should be especially valuable for avian flight muscles.
Riggs
A F
AF
Department of Zoology, University of Texas, Austin, TX 78712, USA. riggs@uts.cc.utexas.edu
D000663:Amphibians / Q000097:blood; D000818:Animals; D001419:Bacteria / Q000378:metabolism; D005399:Fishes / Q000097:blood; D006454:Hemoglobins / Q000378:metabolism*; D007448:Invertebrates / Q000378:metabolism; D008322:Mammals / Q000097:blood; D010100:Oxygen / Q000097:blood*; D011485:Protein Binding; D012104:Reptiles / Q000097:blood
D006454:Hemoglobins; D010100:Oxygen