Hemoglobin, allosteric effects

The allosteric effect is seen in hemoglobin which can exist in two quaternary stmctural states oxygenated (R) or deoxygenated (T). The binding of one O2 or some other effector to one of the subunits stabilizes the R form as compared to the T form. Binding of a second and third O2 stabilizes it even further. 

It was pointed out in Section 6.8 that the term allosteric as coined by MCJ and MWC has been used with three different meanings. In Chapter 6 we discussed the allosteric effect in hemoglobin (Hb). There, the two allosteric sites were identical this has been referred to as the homotropic effect. When the two sites bind different ligands, the heterotropic effect, the induced fit by one ligand can either enhance or diminish the binding affinity of the second ligand (see the example in Section 4.5). 

This expression is called a linked function and indicates how the binding of ligands at nearby sites can influence each other. See also Basic Regulatory Kinetics Cooper-ativity Allosterism Feedback Effectors Bohr Effect Hemoglobin Le Chatelier s Principle Adair Equation... 

Fago, A., E. Bendixen, H. Malte, and R.E. Weber (1997). The anodic hemoglobin of Anguila anguila Molecular basis for allosteric effects in a Root-effect hemoglobin. J. Biol. Chem. 272 15628-15635. 

Gibson QH, Hoffman BM, Crepeau RJH, Edelstein SJ, Bull C. Manganese hemoglobin Allosteric effects in stopped flow flash photolysis and sedimentation measurements. Biochem Biophys Res Commun 1974 59 146. 

The cooperative binding of O2 by hemoglobin and the allosteric effects in many enzymes require interaction between sites that are widely separated in space. The MWC model was proposed in 1965 to incorporate allosteric and conformational effects in an explanation of enzyme cooperativity. The seminal observation was that most cooperative proteins have several identical subunits (protomers) in each molecule (oligomer) this situation is imperative for binding cooperativity. The MWC model is defined as follows ... 

K. Imai, Allosteric Effects in hemoglobin , Cambridge University Press, Cambridge, 1982. 

Allosteric effect of the hemoglobin during oxygen uptake... 

In hemoglobin, four similar units are connected in a tetramer by hydrophobic interactions. Binding of the first oxygen atom enhances the binding constants of the three remaining units. For such cooperative ( allosteric ) effects, which are typical for biological but out of reach for synkinetic systems, the reader is referred to biochemistry textbooks (Dickerson and Geis, 1969,1983 Voets, 1990). 

Komiyama N, Tame J, Nagai K. A hemoglobin-based blood substitute transplanting a novel allosteric effect of crocodile hemoglobin. Biol Chem 1996 377 543-548. 

The oxygen dissociation curve for hemoglobin reflects allosteric effects that result from... 

The cooperative binding of Oj by hemoglobin, and the allosteric effects in many enzymes, requires interactions between sites that are widely separated in space. The present model was proposed in 1965 to... 

The concept of allosteric effects in biology applies beautifully to hemoglobin and cooperative binding of 0>.-... 

J. Wyman, Allosteric Effects in Hemoglobin. Cold Spring Harbor Symp. Quant. BioL, 483-489,1963. 

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