From the Arctic to fetal life: physiological importance and structural basis of an 'additional' chloride-binding site in haemoglobin

Biochem J. 2004 Jun 15;380(Pt 3):889-96. doi: 10.1042/BJ20031421.


Haemoglobins from mammals of sub-Arctic and Arctic species, as well as fetal human Hb, are all characterized by a significantly lower Delta H of oxygenation compared with the majority of mammalian haemoglobins from temperate species (exceptions are represented by some cold-resistant species, such as cow, horse and pig). This has been interpreted as an adaptive mechanism of great importance from a physiological point of view. To date, the molecular basis of this thermodynamic characteristic is still not known. In the present study, we show that binding of extra chloride (with respect to adult human Hb) ions to Hb would significantly contribute to lowering the overall heat of oxygenation, thus providing a molecular basis for the low effect of temperature on the oxygenation-deoxygenation cycle. To this aim, the oxygen binding properties of bovine Hb, bear (Ursus arctos) Hb and horse Hb, which are representative of this series of haemoglobins, have been studied with special regard to the effect of heterotropic ligands, such as organic phosphates (namely 2,3-diphosphoglycerate) and chloride. Functional results are consistent with a mechanism for ligand binding that involves an additional binding site for chloride ion. Analysis of computational chemistry results, obtained by the GRID program, further confirm the hypothesis that the reason for the lower Delta H of oxygenation is mainly due to an increase in the number of the oxygen-linked chloride-binding sites.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • 2,3-Diphosphoglycerate / metabolism
  • Adult
  • Amino Acids / metabolism
  • Amino Acids / physiology
  • Animals
  • Binding Sites / physiology
  • Cattle / blood
  • Chlorides / metabolism*
  • Chlorides / physiology*
  • Computational Biology / methods
  • Computer Simulation
  • Erythrocytes / chemistry
  • Fetal Hemoglobin / chemistry
  • Fetal Hemoglobin / physiology
  • Fetus / blood supply
  • Hemoglobins / chemistry*
  • Hemoglobins / physiology*
  • Horses / blood
  • Humans
  • Oxygen / metabolism
  • Reindeer / blood
  • Species Specificity
  • Swine / blood
  • Thermodynamics
  • Ursidae / blood


  • Amino Acids
  • Chlorides
  • Hemoglobins
  • 2,3-Diphosphoglycerate
  • Fetal Hemoglobin
  • Oxygen