Hemoglobin oxygenated states

Y. Nomura and M. Tamura. Quantitative analysis of hemoglobin oxygenation state of rat brain in vivo by picosecond time-resolved spectrophotometry. Journal of Biochemistry, 109 455-461, 1991. 

In chemistry, it is well known that O2 can be strongly bound to a ferrons iron porphyrin in solvents without any protein matrix however, the oxygenated states of most simple iron porphyrins are irreversibly converted into /r-oxodimers (eqnation3), PFe(III)-0-PFe(III), via peroxo and ferryl intermediates (eqnation 2). The /x-oxodimer is usually very stable in solvents, so it is sometimes called a thermodynamic sink. In addition, autoxidation of PFe(II)-02 to an inert ferric porphyrin easily occurs under aerobic conditions (equation 4). Thus, it is clear that the heme pockets of myoglobin and hemoglobin play an important role in protecting the 02-bound heme from dimerization and autoxidation. 

C. E. Cooper, J. Torres, M. Sharpe, and M. T. Wilson, The Relationship of Oxygen Delivery to Absolute Hemoglobin Oxygenation and Mitochondrial Cytochrome Oxidase Redox State in the Adult Brain a Near-Infrared Spectroscopy Study, Biochem. J., 332, 627 (1998). 

Oxygen and H are not bound at the same sites in hemoglobin. Oxygen binds to the iron atoms of the hemes, whereas H binds to any of several amino acid residues in the protein. A major contribution to the Bohr effect is made by His (His HC3) of the 3 subunits. When protonated, this residue forms one of the ion pairs—to Asp (Asp FGl)—that helps stabilize deoxyhemoglobin in the T state (Fig. 5-9). The ion pair stabilizes the protonated form of His HC3, giving this residue an abnormally high piCa in the T state. The falls to its normal value of 6.0 in the R state because the ion pair cannot form, and this residue is largely unpro-... 

While this concept for the control of erythropoiesis is generally accepted, there are at present insufficient data to determine quantitative relationships among the variables involved. In addition, some auxiliary systems must be included to describe fully the erythropoietic response to stress such as hypoxia. The performance of the respiratory system and the relationships expressed by the oxyhemoglobin dissociation curve affect the oxygenation state of the blood. Blood volume, and in particular plasma volume, affect hemoglobin concentration which limits the amount... 

Manifestation of the Oxygenated State that Prevents Hydrophobic Association of Hemoglobin S Tetramers... 

As with hemoglobin, discussed in Chapter 7, a Bohr effect occurs with cytochrome c oxidase. Again from the viewpoint of the hydrophobic consilient mechanism, these phenomena are analogous. Formation of the less polar states on reduction of Complex IV and on forming deoxyhemoglobin result in proton uptake, whereas formation of the more polar oxidized state of Complex IV and the more polar oxygenated state of hemoglobin result in proton release. This is as expected from the AG, of the comprehensive hydrophobic effect, as discussed above. 

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. 

Reactivity. Hemoglobin can exist ia either of two stmctural coaformatioas, corresponding to the oxy (R, relaxed) or deoxy (T, tense) states. The key differences between these two stmctures are that the constrained T state has a much lower oxygen affinity than the R state and the T state has a lower tendency to dissociate into subunits that can be filtered in the kidneys. Therefore, stabilization of the T conformation would be expected to solve both the oxygen affinity and renal excretion problems. 

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