title: Oxygen delivery and autoxidation of hemoglobin.
abstract: Hemoglobin can be considered to exist in active and inactive states. When the iron atom is in the ferrous form, the protein is active and can bind oxygen reversibly; high and low affinity substates account for the cooperativity of ligand binding. However, like bulk metal, the iron can rust. The oxidation to the ferric form (metHb) leads to an inactive protein. The oxidation rate will therefore limit the useful lifetime of oxygen transporters; this is especially critical for cell free Hb solutions. This problem is compounded by the fact that Hb is a tetramer. A single oxidized heme effects the other three subunits within the same tetramer. The statistics are different from those for a monomeric system. For example, a random distribution of 20% ferric iron would imply 58% of the tetramers with at least one oxidized subunit. The oxidized subunits remain liganded (with water or OH) and will change the oxygenation curve for the neighbouring subunits. Since the tetramer will no longer make a full transition to the deoxy state, the oxygenation curves are shifted towards higher affinities. Thus the oxygen delivery will decrease for two reasons: the direct loss of active hemes, and the secondary influence on the remaining ferrous subunits. Control of the oxidation rate is also complicated by the intercorrelation of parameters. The rate is globally correlated with the oxygen affinity; it is also increased for hemoglobin dimers relative to tetramers. One must therefore accept a compromise of these parameters, in order to obtain a useful transporter.
authors.affiliation: Institut National de la Santé et de la Recherche Médicale, Unité 299, Hôpital de Bicêtre, Le Kremlin-Bicêtre, France.
authors.forename: M C
authors.initials: MC
authors.lastname: Marden
authors.forename: N
authors.initials: N
authors.lastname: Griffon
authors.forename: C
authors.initials: C
authors.lastname: Poyart
mesh_terms: D001692:Biological Transport; D006454:Hemoglobins / Q000378:metabolism*; D006801:Humans; D010084:Oxidation-Reduction; D010100:Oxygen / Q000097:blood*; D010313:Partial Pressure
chemical_list: D006454:Hemoglobins; D010100:Oxygen