Cooperative effect, hemoglobin

Non-statistical successive binding of O2 and CO to the four heme centers of hemoglobin ( cooperativity ) has been thoroughly documented. It is difficult to test for a similar effect for NO since the equilibrium constants are very large ( 10 M ) and therefore difficult to measure accurately. It is found that the four successive formation rate constants for binding NO to hemoglobin are identical. In contrast, the rate constant for dissociation of the first NO from Hb(NO)4 is at least 80 times less than that for removal of NO from the singly bound entity Hb(NO). This demonstrates cooperativity for the system, and shows that it resides in the dissociation process. The thermodynamic implications of any kinetic data should therefore always be assessed. 

ADAIR EQUATION COOPERATIVE LIGAND BINDING HILL EQUATION PLOT KOSHLAND-NEMETHY-EILMER MODEL MONOD-WYMAN-CHANCEUX MODEL NEGATIVE COOPERATIVITY POSITIVE COOPERATIVITY HEMOGLOBIN ALLOTOPIC EFFECT Allowed electronic transitions,... 

The stereochemical mechanism of the cooperative effects in hemoglobin revisited. Annu. Rev. Biophys. Biomol. Struct. 27, 1-34. 

Upon oxygenation of hemoglobin, two of the heme groups move about 100 pm towards each other while two others separate by about 700 pm Perhaps a better way of describing the movement is to say that one aP half of the molecule rotates 15° relative to the other half.30 These movements are the result of a change in the quaternary structure of the hemoglobin and are responsible for the cooperative effects observed. The quaternary structure exhibited by the deoxy form is called the T state. 

The deoxy-oxy shift on binding oxygen in one hemoglobin molecule. The projection shown in this figure is approximately perpendicular to the one shown in figure 5.6. The atfl] dimer moves as a unit relative to the a2jS2 dimer. The interface between the two dimers is crucial to the cooperativity effect in... 

Of greatest interest are those compounds that attempt to model hemoglobin directly. Simple iron(II) porphyrins are readily autoxidized first to superoxo species, then to //-peroxo dimers and finally to /x-oxo dimers, as represented in equation (60). Bridge formation must be prevented if carrier properties are to be observed. This has been achieved by the use of low temperature and sterically hindered or immobilized iron(II) porphyrins. Irreversible oxidation is also hindered by the use of hydrophobic environments. In addition, model porphyrins should be five-coordinate to allow the ready binding of 02 this requires that one side should be protected with a hydrophobic structure. Attempts have also been made to investigate the cooperative effect by studying models in which different degrees of strain have been introduced. 

The molecular basis for the cooperativity effects in hemoglobins has been worked out in some detail. However, before delving into that, it is necessary to... 

The possible mechanistic importance of the Fe-imidazole(histidine) bond, especially in various models for hemoglobin cooperativity, has been recognized for some time. NRVS clearly provides the first experimental method for systematic studies of how the Fe-Im bond strength can be modulated in six-coordinate hemes, both by protein environmental effects as well as by the consequences of systematic ligand change. 

M.F. Perutz, A.J. Wilkinson, M. Paoli, and G.G Dodson. 1998. The stereochemical mechanism of the cooperative effects in hemoglobin revisited Rev. Biophys. Biomol. Struct. 27 1-34. (PubMed)... 

More recently Perutz (PIO) has proposed a stereochemical mechanism of heme-heme interaction which describes in detail the cooperative effects in hemoglobin. Most important in the oxygenation-deoxygenation... 

Fig. 3. Diagrammatic sketch showing the change in tertiary structure of a hemoglobin a chain on reaction with oxygen. Movement of the iron atom into the plane of the porphyrin ring causes a movement of helix F toward helix H, which expels tyrosine in position 140 from its pocket between the two helices. From (PIO), M. F. Perutz, Stereochemistry of cooperative effects in haemoglobin. Nature (London) 228, 726 (1970) with permission of the author and publisher.

Uptake of Oj is associated with substantial conformational changes, which are central to an understanding of the cooperative effect. These conformational changes are associated with the reversible interconversion of a tensed (T), low affinity form of hemoglobin into a relaxed (R) high affinity form. 

Coordination Compounds in Biology 62.1.12.3.3 The cooperative effect in hemoglobin... 

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