Cooperativity, hemoglobin

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 transition between the T and R states of hemoglobin is also deeply involved in the Bohr effect and cooperativity. Therefore stabilization of either of the two stmctures should diminish these effects, which have important physiologic consequences. The clinical consequences of stabilization are not known. 

The oxygen affinity of the derivative was shown to be about half that of unmodified hemoglobin under similar conditions, but a degree of cooperativity was preserved. Kquilihrium and kinetic ligand-binding studies on this derivative have been interpreted (62) to show a perturbed R state. It is beheved that although the reaction is between the two P-chains, aP-dimers function independentiy, probably through a flexible connection. 

Optimization of the ATP—hemoglobin reaction conditions produced a preparation having a markedly reduced oxygen affinity. Five fractions from a reaction mixture, when isolated, were found to have P q values ranging from 1.1 to 5.0 kPa (8 to 38 torr), most withUtfle cooperativity (118). These results are consistent with those found with other polyfunctional reagents that react on the surface of hemoglobin. 

The Physiological Significance of Cooperative Binding of Oxygen by Hemoglobin... 

As noted, hemoglobin is an tetramer. Each of the four subunits has a conformation virtually identical to that of myoglobin. Two different types of subunits, a and /3, are necessary to achieve cooperative Oa-binding by Hb. The /3-chain at 146 amino acid residues is shorter than the myoglobin chain (153 residues), mainly because its final helical segment (the H helix) is shorter. The a-chain (141 residues) also has a shortened H helix and lacks the D helix as well (Figure 15.28). Max Perutz, who has devoted his life to elucidating the atomic structure of Hb, noted very early in his studies that the molecule was... 

We can determine quantitatively the physiological significance of the sigmoid nature of the hemoglobin oxygen-binding curve, or, in other words, the biological importance of cooperativity. The equation... 

Spin-pairing model of dioxygen binding and its application to various transition metal systems as well as hemoglobin cooperativity. R. S. Drago and B. B. Corden, Acc. Chem. Res., 1980, 13, 353-360 (39). 

Hemoglobins bind four molecules of Oj per tetramer, one per heme. A molecule of Oj binds to a hemoglobin tetramer more readily if other Oj molecules are already bound (Figure 6-4). Termed cooperative binding, this phenomenon permits hemoglobin to maximize both the quantity of O2 loaded at the PO2 of the lungs and the quantity of O2 released at the PO2 of the peripheral tissues. Gooperative interactions, an exclusive property of multimeric proteins, are critically important to aerobic life. 

The 02-binding curve for myoglobin is hyperbolic, but for hemoglobin it is sigmoidal, a consequence of cooperative interactions in the tetramer. Cooperativ-ity maximizes the ability of hemoglobin both to load O2 at the PO2 of the lungs and to deliver O2 at the PO2 of the tissues. 

Some preliminary ENDOR investigations of the fascinating cooperative oxygenation effect in hemoglobin have been reported by Feher et al.243). Since magnetic resonance... 

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