The Structure and Function of Hemoglobin: Gilbert Smithson Adair and the Adair Equations
Year: 2002
Type: article
Abstract: 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 (1Edsall J.T. Memories of early days in protein science..Protein Sci. 1992; 1: 1526-1530Crossref PubMed Scopus (8) Google Scholar). Edsall spent two years in the laboratory of F. Gowland Hopkins at Cambridge, the author of a previous Journal of Biological Chemistry (JBC) Classic (2Hopkins F.G. Dixon M. J. Biol. Chem... 1922; 54 (JBC Classics:): 1527-1563http://www.jbc.org/cgi/content/full/277/24/e13Google Scholar), 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.
Source: Journal of Biological Chemistry
Language: English
Subfield: Cell Biology
Domain: Life Sciences
Open Access status: hybrid
Estimated APC paid: $3,430
OpenAlex ID: W1534563471