Fixed charge hypothesis

A stopped-flow rapid-reaction apparatus was used to measure the time course of pH changes in human erythrocyte suspensions. In one set of experiments a red cell suspension at pH 72 was mixed with an isotonic saline solution whose pH had been adjusted to a value between 2.1 and 10.4. Analysis of the results enabled computation of erythrocyte hydroxyl ion permeability as a function of pH. Further experiments were then performed in which erythrocyte suspensions at low pco2 were mixed with bicarbonate solutions at high pco2- Analysis revealed that C02 equilibrium in the mixture was reached quickly, but pH equilibrium was delayed. Evaluation of the results indicates that variation in red cell OH permeability with pH is not compatible with a simple fixed-charge hypothesis of membrane permselectivity, and the uncatalyzed hydration-dehydration of C02 in extracellular fluid is required to produce pH equilibration after blood-gas exchange. 

Fixed Charge Hypothesis. According to the computation described above, the movement of an ion across the red cell membrane is governed by its concentration gradient and the transmembrane potential. It has been suggested (33) that the membrane potential is one factor that, in addition to its direct effect on flux, is a determinant of ionic permeability. For cation movements over wide ranges of membrane potential, a relatively small dependence of permeability on potential has been demonstrated (34). 

The study of the fixed-charge hypothesis is ideally carried out by steady-state isotopic permeability experiments. These conditions are impossible to meet in the study of hydroxyl ion movements. Furthermore, net OH" movements necessarily involve pH changes by their nature. Nevertheless, the experiments reported here can be used to determine the effects of external pH on OH" permeability since temperature and... 

The association-induction hypothesis was in its early days known as Ling s fixed-charge hypothesis. In years following, the theory has evolved. The newer version plus results of more than 30 years of experimental testing are presented in a book called In Search of the Physical Basis of Life (Gilbert N. Ling, Plenum Press, 1984). The following is a brief sketch of the key features of the AI hypothesis. 

From the latter data it is possible to estimate a value of 4.10 (1/equiv) for the apparent equilibrium constant of Cu " " binding, on the hypothesis that it simply involves one fixed alginate charge per Cu " " ion bound and no interdependence between binding sites. Consequently, one also estimates that AGg = -4.9 (kcal per mole of binding reaction), and that in the calorimetric and dilatometric experiments at, say, [ Cu ]/N = 0.05 more than 90% of the Cu ions present in solution are linked to alginate chains. 

With respect to the formulation given by Eq. (13.27) in which a characteristic time was considered tf, now a constant charge density 2 is fixed and the time tf depends on Q that, in turn, varies with environmental conditions. As a proof of this hypothesis, it has been observed [34] that L is of the order of 0.5-1 pm that represents just the typical diameter of dislocation cells. Once 2 is fixed. Ford [35] introduces an apparently contradictory concepts stating that now g is also function of the stress field ahead of the crack tip whose amplitude is defined by the stress intensity factor Kj — a Ja fia), according to a relationship of the type... 

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