The chloride effect in the human embryonic haemoglobins

Abstract

The interactions of the three human embryonic haemoglobins with chloride ions have been investigated. Each of the three embryonic haemoglobins exhibits a unique pattern of oxygen-affinity-dependence on chloride ion concentration. Human embryonic haemoglobin Portland (zeta 2 gamma 2) is found to be completely insensitive to chloride ion concentration. Haemoglobin Gower I (zeta 2 gamma 2) shows a small concentration dependence, whilst haemoglobin Gower II (alpha 2 epsilon 2) exhibits a dependence approaching that of the adult protein. The degree of co-operativity for each protein is essentially chloride concentration independent. The chloride-dependent and -independent components of the alkaline Bohr effects have been measured for each of the embryonic haemoglobins and compared with that of the adult protein. Both the chloride-binding data and the Bohr effect have been analysed in terms of the recently developed allosteric model proposed by Perutz [Perutz, Fermi, Poyart, Pagnier and Kister (1993) J. Mol. Biol. 233, 536-545].

Genetic differences in hemoglobin function between highland and lowland deer mice

“…Differences in Cl -sensitivity are associated with differences in Cl -binding constants: 0.127±0.027moll -1 and 0.104±0.025moll -1 for highland and lowland mice, respectively. These values are similar to those for other vertebrate Hbs (Antonini and Brunori, 1971;Weber, 1992;Hofmann et al, 1995) and are close to the Cl -concentration normally present in the vertebrate red blood cell (0.1moll -1 ). A relatively greater allosteric effect of Cl -ions than of DPG on Hb-O 2 affinity has also been reported for house mice Mus musculus (Runck et al, 2010), and may be a feature shared by other rodents.…”

Molecular and physicochemical characterization of hemoglobin from the high-altitude Taiwanese brown-toothed shrew (Episoriculus fumidus)

“…As with DPG, we found the chloride sensitivity (Log P 50 Hofmann et al 1995). It has been shown that the difference between the two human Hbs (i.e.…”

Origin of the Suppression of Chloride Ion Sensitivity in Human Embryonic Hemoglobin Gower II

“…For the family of three human embryonic hemoglobins produced during the embryonic stage of human development, the situation is somewhat more complex. The two f chain-containing proteins are almost devoid of a response to chloride ions, whereas the a 2 e 2 protein (hemoglobin Gower II) shows a substantial chloride ion response, which is 40% less than that seen in the case of the adult protein (6). These differences in response observed for the f chain-containing proteins can, in the main, be explained in terms of amino acid differences at the sites identi ed as controlling the chloride effect in the adult protein (3).…”

“…In the case of the a 2 e 2 protein, however, the diminished chloride ion effect does not correspond to any simple replacement of these key amino acids. Close comparison of the amino acid sequences of the embryonic e and adult b chains has lead to the suggestion that any of three possible amino acid changes between the chains might be responsible for the lowering of the sensitivity towards chloride ions observed in the e chain-containing protein (6). The three residues proposed as possible candidates are His b 116!…”