Bohr effect, hemoglobin

Manz, B Stilbs, P Jonsson, B Soderman, O Callaghan, PT, NMR Imaging of the Time Evolution of Electroosmotic Flow in a Capillary, Journal of Physical Chemistry 99, 11297, 1995. Matthew, JB Hanania, GIH Gurd, FRN, Electrostatic Effects in Hemoglobin Bohr Effect and Ionic Strength Dependence of Individual Groups, Biochemistry 18, 1928, 1979. 

RESONANCE RAMAN SPECTROSCOPY HEMOGLOBIN BOHR EFFECT... 

The most important and universal type of chemical equilibria to which a heme protein is subjected in natural environments is pH equilibria, involving the protein aminoacid residues and the ionizable groups of the porphyrin, the propionate side chains. Beside the effects on the overall protein structure, which are outside the scope of this review, the major consequences of proton equilibria may be the changes of the heme reduction potential (electron affinity), called the redox-Bohr effect (see Sect. 3.2), by analogy to the pH effect on the oxygen affinity of hemoglobin (Bohr effect). 

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. 

In 1982 a study of the usefulness of DBBF in the production of a blood substitute was reported (99). A single modification achieved the dual goals of reduced oxygen affinity and restricted tetramer—dimer dissociation. This work was confirmed in 1987 (98). The product, called aa-hemoglobin, was formulated in Ringer s lactate. P q under physiologic conditions is 3.7 kPa (28.0 torr). Hill s parameter is 2.2, and the Bohr effect was reduced (100). Plasma retention was increased, and the product appeared to be less heterogeneous than some of the other derivatives under study. Its production was scaled up by Baxter Healthcare Corp., under contract to the U.S. Army. 

Figure 6-9. The Bohr effect. Carbon dioxide generated in peripheral tissues combines with water to form carbonic acid, which dissociates into protons and bicarbonate ions. Deoxyhemoglobin acts as a buffer by binding protons and delivering them to the lungs. In the lungs, the uptake of oxygen by hemoglobin releases protons that combine with bicarbonate ion, forming carbonic acid, which when dehydrated by carbonic anhydrase becomes carbon dioxide, which then is exhaled.

In hemoglobin M, histidine F8 (His F8) has been replaced by tyrosine. The iron of HbM forms a tight ionic complex with the phenolate anion of tyrosine that stabilizes the Fc3 form. In a-chain hemoglobin M variants, the R-T equilibrium favors the T state. Oxygen affinity is reduced, and the Bohr effect is absent. P Ghain hemoglobin M variants exhibit R-T switching, and the Bohr effect is therefore present. 

Hemoglobin s dioxygen binding is regulated by local concentrations of H+ (known as the Bohr effect), CO2 concentration, and organic phosphates such as diphosphoglycerate (DPG), whose structure is shown in Figure 4.2.17... 

To produce a strong alkaline Bohr effect and a Root effect at acid pH, Xenopus hemoglobin has conserved the essential Ser F9/3, Glu FGljS, and... 

In another aquatic f rog, Amphiuma, the adult hemoglobin has an acid Bohr effect at physiological pH, converted in vivo to a weak alkaline one... 

O2 binding to Hb is regulated by H" ions (i.e., by the pH value) via the same mechanism. High concentrations of CO2 such as those in tissues with intensive metabolism locally increase the H" concentration and thereby reduce hemoglobin s O2 af nity (Bohr effect see above). This leads to increased O2 release and thus to an improved oxygen supply. 

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... 

BASIC REGULATORY KINETICS BOHR EFFECT COOPERATIVITY FEEDBACK EFFECTORS LE CHATELIER S PRINCIPLE HEMOGLOBIN ADAIR EQUATION LINOLEATE ISOMERASE Linoleoyl ester,... 

Hemoglobin also binds H+ and C02, resulting in the formation of ion pairs that stabilize the T state and lessen the protein s affinity for 02 (the Bohr effect). Oxygen binding to hemoglobin is also modulated by 2,3-bisphosphoglycerate, which binds to and stabilizes the T state. 

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