A possible role for protein dissociation in the functioning of embryonic haemoglobins.

Abstract

ABSTRACT During early mammalian development the changing demands for oxygen in embryonic tissues are met, in part, by the synthesis of a series of embryonic haemoglobins. At the earliest stages of development three embryonic haemoglobins are synthesized in both humans and mice (Melderis, Steinheider & Ostertag, 1974; Shimizu & Watanabe, 1978; Brotherton, Chui, Gauldie & Patterson, 1979; Purdie, Wells & Brittain, 1983; Brittain & Wells, 1983). The proportions of each haemoglobin present in the mouse red blood cells vary significantly from the ninth day of gestation until parturition (Purdie et al. 1983). Although studies have been made on this developmental system of gene switching and haemoglobin composition (Brotherton et al. 1979) very few studies have been made on the functional characteristics of these embryonic haemoglobins, mainly because of the limited amount of material available (Bauer et al. 1975 ; Brittain & Wells, 1983 ; Purdie et al. 1983). The oxygen binding curves for whole blood from the earliest embryos show anomalous binding patterns (Wells & Brittain, 1981; Purdie et al. 1983; Brittain & Wells, 1983). The high oxygen affinity component present in the red blood cells of early embryonic mice has been correlated with the presence of embryonic haemoglobin El, which has a subunit structure χ2ϵ2 (Melderis et al. 1974). This haemoglobin species El shows very low cooperativity in both its equilibrium and kinetic functions (Purdie et al. 1983; Brittain, Sutherland & Greenwood, 1986). Recent investigations have indicated that the functioning of this haemoglobin is not related to any unusual redox balance within the embryonic red blood cell (Brittain & Tottle, 1986) and thus the occurrence of an essentially non-cooperative haemoglobin with a tetrameric subunit structure has posed something of a paradox. This study presents data on the dimerization of mouse embryonic haemoglobin El over a range of conditions and, together with numerical simulations of oxygen binding curves, illustrates how, within the early embryonic red blood cell, high oxygen affinity and sensitivity to pH may be obtained by protein dimerization.