Triple-point behaviour of human haemoglobin

Abstract

The recent crystallographic observation of Brzozowski et al.¹ demonstrates the existence of half-oxygenated haemoglobin crystals. At first sight this seems to imply the discovery of a unique molecule, defined by exactly two bound oxygens. However, the formation of crystals with a specific degree of ligation is predicted to occur when two distinct crystalline phases coexist, namely at the triple point². It seems likely that the crystals studied by Brzozowski et al.¹ were selected from a mixture of T and R crystalline forms obtained in conditions where the triple point existed. In general, the equilibria between haemoglobin solid and liquid phases are governed by the chemical potential of a control ligand and the ligand-binding properties of each phase. We report here that a unique situation arises when there are two different crystalline phases, each with characteristic oxygen-binding properties. One can then predict the existence of a triple point, defined by a specific oxygen partial pressure, where both solid phases coexist². At this point the degree of oxygen saturation in each solid phase is uniquely specified. These considerations could explain the specifically ligated crystals found by Brzozowski et al.¹.