These are preliminary reports that have not been peer-reviewed. They should not be regarded as conclusive, guide clinical practice/health-related behavior, or be reported in news media as established information. For more information, please see our FAQs.
Essay Five.pdf (254.89 kB)

Resolution of the Equilibrium Constant for the T State → RState Conformational Change of Human Hemoglobin into Endothermic and Exothermic Component Reactions

submitted on 22.11.2019 and posted on 29.11.2019 by Francis Knowles, Douglas Magde

The dimensionless equilibrium constant for the allosteric conformation change, KΔC = 0.02602 (Knowles & Magde, linked ms 2) following binding of O2 by α-chains in Tstate Hb4/BPG (whole blood under standard conditions) is shown to be comprised of: (i) an endothermic change in conformation, from Tstate to Rstate, of 24.3 kJ/mol; (ii) exothermic conversion of Tstate TαO2-chains to Rstate RαO2-chains of -13.8 kJ/mol; (iii)exothermic binding of BPG by R-states. Eq. (1) defines the component steps whereby the Tstate conformation is converted to the Rstate conformation.

ΔGo(R(Hb4), BPG) describes the endothermic decomposition of the binary complex, THb4/BPG into RHb4 and BPG, equal to + 33.7 kJ/mol (DeBruin et al. (1973). J. Biol. Chem. 248, 2774-2777). ΔGo for the equilibrium constant for ΔGO(KΔC) and Σ ΔGo for binding of O2 by the pair of equivalent Tstate α-chains, ΔGO(Tα*O2), + 9.41 kJ/mol and – 49.6 kJ/mol, respectively, are determined by fitting of O2 equilibrium binding data to the Perutz-Adair equation. ΔGo for reaction of a pair of equivalent Rstate α-chains with O2, ΔGO(RαO2), was estimated from the known affinity of myoglobin for O2 at 37oC (Theorell H. (1936). Biochem. Z., 268, 73-81), -63.4 kJ/mol. The unknown quantity, ∆GO(R(HbO2)4/BPG), was obtained by solving Eq. (1), being -10.5 kJ/mol, K (R(HbO2)4/BPG) = 58.4 L/mol. The value of the equilibrium constant for binding BPG to R-state conformations represents 0.0073% of the value of the binding constant of BPG to Tstate conformations: 800,000 L/mol. The value of KΔC; (i) accounts for the ability of O2 to escape, virtually unhindered from rbcs and (ii) provides a biophysical basis for manifestation of high resting rates of metabolism in warm blooded species.




Email Address of Submitting Author


University of California, San Diego



ORCID For Submitting Author


Declaration of Conflict of Interest

No conflict of interest