Kosmotropicity

Hydrophobic Interaction Chromatography. Hydrophobic interactions of solutes with a stationary phase result in thek adsorption on neutral or mildly hydrophobic stationary phases. The solutes are adsorbed at a high salt concentration, and then desorbed in order of increasing surface hydrophobicity, in a decreasing kosmotrope gradient. This characteristic follows the order of the lyotropic series for the anions ... 

METABOLIC CHANNELING CHAOTROPIC AGENTS HOFMEISTER SERIES KOSMOTROPES... 

HOFMEISTER SERIES CHAOTROPIC AGENTS KOSMOTROPES Hofstee plot,... 

COOPERATIVITY ALLOSTERISM INDUCED FIT MODEL MONOD-WYMAN-CHANGEUX MODEL INDEPENDENT BINDING LINKED FUNCTIONS ADAIR EQUATION POSITIVE COOPERATIVITY NEGATIVE COOPERATIVITY KOSMOTROPES CHAOTROPIC AGENTS HOFMEISTER SERIES Kp, Kq, K .. . ... 

In fact, halophilic enzymes have been shown to function in low salt environments, where the salt is replaced by a suitable organic solvent typically those that are kosmotropic. For example, an extracellular protease from H. halobium, which requires 4M NaCl for optimal function, is highly active in as little as 0.2 M NaCl in the presence of 40% (v/v) dimethylsulfoxide (DMSO) [10]. The behavior of salts... 

Figure 3.2 Replacement of high salt with organic solvents-stability of the extracellular protease from Halobacterium halobium in 0.36 M NaCl in water or various organic solvents. The KSC value represents the Sechenow constant multiplied by the concentration of the solvent, which provides a measure of the salting-out (kosmotropic) capacity of the solution [10].

These results were then correlated to the Jones-Dole coefficient to investigate the dependence of enzyme activation on the kosmotropicity of the salt in a solvent such as hexane. Specifically, plotting enzyme activity as a function of the difference in J DB coefficients of the cations and anions of the salts, resulted in a clear trend towards increased enzyme activity when the difference between the kosmotropicity of the anion and the chaotropicity of the cation was increased (Figure 3.10) [46]. These results were consistent with those of Ru et al. [33], in that enzyme activity in salt-activated preparations in hexane positively correlates with increased kosmotropicity on the anion. As a result of the elucidation of the influence of the kosmotropic/chaotropic properties of salts on enzyme function, the role of water... 

Figure 3.10 Correlation between the observed reactivity of penicillin amidase formulations and the difference in the Jones-Dole coefficients of the kosmotropic anion and the chaotropic cation for single salt and binary salt mixtures [46].

At high substrate concentration, chaotropic or kosmotropic effects can occur,... 

Figure 8.6 Hofmeister series of kosmotropic and chaotropic ions.

It is apparent from Figure 8.6 that the use of ammonium sulfate for protein precipitation is rationalized with the salt s kosmotropic properties in addition, (NH4)2S04 is highly soluble in aqueous solution. 

The second attempt describes the influence of salt as an interaction of chaotropes and kosmotropes with layers of hydration on the surface of the respective ion. This interaction can be captured by measuring relative viscosity as a function of salt concentration or ionic strength (Jones, 1929) [Eq. (8.60)]. 

Here r/0 is the viscosity in salt-free medium and A and B are constants at high salt concentrations, the second term becomes irrelevant. The constant B, which is the second virial coefficient signifying ion-solvent interactions, is termed the Jones-Dole coefficient after the inventors (Jones, 1929). Chaotropes have a coefficient B which is less than zero, whereas kosmotropes are characterized by 1 > 0. 

Addition of kosmotropic salts such as (NH4)2S04 or KH2P04 to the system enhances KP, as the protein is salted out of the bottom phase. 

The unfolded state U is modeled as a single conformation even though this is by no means obvious and usually cannot be verified. The unfolding equilibrium between N and U can be shifted to the unfolded form by measures such as an increase in temperature or an increase in the concentration of structure breakers , termed chaotropes, such as urea or guanidinium hydrochloride. When either temperature or the concentration of chaotropes is decreased (or the concentration of structure formers , kosmotropes, is increased), the folding equilibrium reverts to the native state N. The two-state model is an approximation very often, analytically verified folding intermediates render the two-state model incomplete. 

At a high concentration of substrate, product, or inhibitor, these compounds can exert a chaotropic or kosmotropic effect, regardless of their ability to interact with the active site of the enzyme. 

One group of kosmotropic stabilizers of proteins are the osmolytes, organic osmoprotectant solutes, mostly polyhydric alcohols and amino acids or their derivatives. Osmolyte compatibility of organisms is thought to result from absence of osmolyte interactions with substrates and cofactors, and the non-perturbing or favorable effects on macromolecular-solvent interactions (Yancey, 1982). 

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