title: Hemoglobin, pH and DPG/chloride shifting.
abstract: In this study a decreased DPG response by polar bear (Ursus maritimus) hemoglobin was observed, and this response was interpreted as an example of gradual DPG/chloride shifting. This sort of mechanism has been suggested to occur in ruminants and, intuitively, one might guess that for ruminants the DPG/Cl- shifting might have been beneficial and hence selected for at the time of the latest Ice Age. However, suggestion that this is purely a temperature effect in polar bears and ruminants conflicts with the existence, in the hot savanna, of mammals that have Hb modulated by chloride. However, acidosis effects caused by routine periods of food shortage, induced in extreme environments may explain the responses of the hemoglobins of animals adapted to extreme habitats. The chloride effect is bound to specific amino acid substitutions in key positions. In polar bear Hb, they are specific, additional (with respect to human HbA) O2-linked chloride binding sites located between Lys-76 (beta) and Lys-8 (beta). The amino acids operate as an additional H+ binding site for a chloride anion. Additionally, with respect to human adult HbA, the primary structure of polar bear Hb was characterized by two substitutions in beta chains: Pro-5 (A2)--> Gly and Ala-76 (E20)-->Lys. The increased flexibility of the A helix causes the lower DPG effect. We further hypothesize that the resulting widening of the central cavity allows the Lys-82 (beta) terminus to be free and constitute an additional, chloride-binding site.
authors.affiliation: Istituto di Biochimica, UCSC, Facoltà di Medicina, Largo F, Vito 1, 00168 Rome, Italy. m.pomponi@rm.unicatt.it
authors.forename: Massimo
authors.initials: M
authors.lastname: Pomponi
authors.forename: Enrico
authors.initials: E
authors.lastname: Gavuzzo
authors.forename: Claudia
authors.initials: C
authors.lastname: Bertonati
authors.forename: Andrew E
authors.initials: AE
authors.lastname: Derocher
authors.forename: Christian
authors.initials: C
authors.lastname: Lydersen
authors.forename: Øystein
authors.initials: Ø
authors.lastname: Wiig
authors.forename: Kit M
authors.initials: KM
authors.lastname: Kovacs
mesh_terms: D000595:Amino Acid Sequence; D019943:Amino Acid Substitution; D000818:Animals; D001665:Binding Sites; D002712:Chlorides / Q000737:chemistry*; D004163:Diphosphoglyceric Acids / Q000378:metabolism*; D005998:Glycine / Q000378:metabolism; D006454:Hemoglobins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D006863:Hydrogen-Ion Concentration; D008239:Lysine / Q000378:metabolism; D008958:Models, Molecular; D008969:Molecular Sequence Data; D015394:Molecular Structure; D019906:Nuclear Magnetic Resonance, Biomolecular; D010100:Oxygen / Q000378:metabolism; D010759:Phosphorus Isotopes / Q000378:metabolism; D011485:Protein Binding; D017433:Protein Structure, Secondary; D011522:Protons; D017386:Sequence Homology, Amino Acid; D001503:Ursidae / Q000097:blood*
chemical_list: D002712:Chlorides; D004163:Diphosphoglyceric Acids; D006454:Hemoglobins; D010759:Phosphorus Isotopes; D011522:Protons; D008239:Lysine; D010100:Oxygen; D005998:Glycine