Relationship Between Spin State, Conformation and Functional Properties in Human Hemoglobin

It is generally accepted that there is a thermodynamic linkage in carp hemoglobin between the spin equilibria of ferric derivatives and the quaternary state of the protein. The average free energy of this linkage is about 700 cal/mole of heme. Evidence that this relationship is a general one and also applies, for example, to the human protein has been lacking. Although liganded derivatives of human hemoglobin, HbA, cannot generally be converted to their T states, Perutz et al. (Biochemistry (1974) 13, 2174) presented evidence that IHP can produce such a transition with high spin ferric derivatives. Philo and Dreyer (Biochemistry (1985) 24, 2985) examined the effect of IHP on the magnetic susceptibilities of several high spin derivatives of HbA and concluded that the linkage free energy was much smaller than for the carp protein and in some cases virtually nil.