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The Hemoglobin System. VI. The Oxygen
Dissociation Curve of Hemoglobin (Adair, G. S. (1925)
J. Biol. Chem. 63, 529-545)
Gilbert Smithson Adair (1896-1979) was a pioneer in the
application of physical chemistry to the study of proteins. He was born
in Whitehaven, England and received much of his early schooling at
home. He entered King's College, Cambridge, in 1915 and received a
first class degree in natural sciences in 1917. After graduation he
joined the Food Investigation Board, which was considering ways to
prevent the spoilage of food sent on cargo ships. He returned to
King's College in 1920 as a research student, and in 1928 he was made
an official Fellow of the College, which allowed him to devote five
years to research. In 1931 he became assistant director of the
Physiological Laboratory at Cambridge, and in 1945 he was named Reader
in Biophysics, the post he held until retiring in 1963.
John Edsall described Adair as the person most influential in shaping
his career as a young protein chemist (1). Edsall spent two years in
the laboratory of F. Gowland Hopkins at Cambridge, the author of a
previous Journal of Biological Chemistry (JBC) Classic (2),
between his second and third years as a medical student at Harvard.
During the time at Cambridge, Edsall met and interacted with Adair.
Early in his career, Adair resolved a long standing controversy about
the molecular weight of hemoglobin. It was widely agreed, primarily
from measurements of iron content, that the minimum molecular weight of
hemoglobin was about 16,000, but there was little agreement about what
multiple of 16,000 was correct. Using osmotic pressure measurements,
which he had pioneered, and five years of work, Adair was able to
demonstrate that the molecular weight of hemoglobin was 4 × 16,000. This conclusion was controversial, because most still thought
that the true molecular weight was 16,000. Several months later, and
not knowing of Adair's work, The Svedberg in Uppsala, using his newly
developed analytical ultracentrifuge, demonstrated that Adair's
molecular weight for hemoglobin was correct.
The work reported in this JBC Classic describes the oxygen-binding
properties of pure hemoglobin under various conditions. This study is
one of the first on ligand binding by hemoglobin in a pure system, as
blood had been used in most previous studies. Adair concluded that
Hb(O2)4 dissociates in stages to Hb + 4 (O2). It was clear that oxygen binding by hemoglobin could
not be explained by the well known law of mass action, which gives rise
to a hyperbolic binding curve, and thus contradicted the proposals of
A. V. Hill and J. B. S. Haldane, themselves giants in
physical chemistry. The binding curves that Adair obtained are clearly
sigmoidal, defining a much more complex binding mechanism,
i.e. cooperativity. The data presented in Fig. 1 of this JBC
Classic are stunning for their precision and show clearly both the
cooperativity and the pH dependence of oxygen binding, two hallmarks of
the physiological function of hemoglobin. Adair had established the
analytical basis and theoretical framework for describing the
phenomenon of cooperative oxygen binding by hemoglobin although it was
only many years later that the mechanism was understood. The Adair
equations that describe oxygen binding are still used today.
It is interesting that Adair provided the first crystals of horse
hemoglobin to Max Perutz, as Perutz began his historic work on
hemoglobin structure. By 1968, with elucidation of the structure of
hemoglobin at atomic resolution, the mechanism of the cooperative binding of oxygen by hemoglobin that Adair had reported 43 years earlier was understood in structural terms. Adair was elected a Fellow
of the Royal Society in 1939.
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