Transporter allosteric effect

Other approaches to self-assembling receptors have been reported in recent years. A self-assembling, trimeric palladium complex based on the bis(benzimidazole) ligand (17) was designed by Williams and coworkers [4]. The complex contains a hydrophobic cavity that in the X-ray structure has included a molecule of acetonitrile. In a different context, Schepartz and McDevitt [70] have used the chelation of nickel(n) by A,7V -bis(salicylaldehy-de)ethylenediamine (salen) derivatives to control the position of K -binding glyme chains, and it has been shown that these self-assembled ionophores influence alkali metal transport across liquid membranes [71]. Also, Shinkai and coworkers [72] and Schneider and Ruf [73] have used metal chelation to induce an allosteric effect on binding at a second site. 

The receptor-mediated, presynaptic, negative-feedback mechanisms are rapidly activated after administration of tricyclic antidepressants. By limiting synaptic availability of NE, such mechanisms normally tend to maintain functional homeostasis. However, with repeated drug exposure, Qj-receptor responses eventually are diminished, possibly from desensitization secondary to increased exposure to the endogenous agonist (NE) or from prolonged occnpation of the NE transporter itself via an allosteric effect. Over a period of days to weeks, this adaptation allows the presynaptic production and release of NE to return to, or even exceed, baseline levels. However, long-term treatment eventually can reduce the expression of tyrosine hydroxylase as well as the NE transporter. 

Y. Kashimori, T. Kikuchi, and K. Nishimoto, The Solitonic Mechanism for Proton Transport in a Hydrogen Bonded Chian, J. Chem. Phys. 77, 1904-1907 (1982) cf. also T. Kikuchi and K. Nishimoto, Theoretical Studies of Hemoproteins, I. Mathematical Description of the Allosteric Effect, Int. J. Quantum Chem. 15, 379-387 (1979). 

Pseudocrown ethers, whose structures are maintained by coordination bonds instead of covalent bonds like typical crown ethers, are among the most suitable candidates for allosteric regulation of ion binding. A linear podand 2 possessing bipyridine moieties at the ends of the polyether chain was converted easily to the corresponding pseudocrown ether quantitatively by complexation with Cu+ (Scheme 1.1). The pseudocrown ether shows a positive allosteric effect on alkali metal ion selectivity in ion transport. The drastic conformational change from a linear to cyclic structure results in a significant macrocyclic effect favorable for ion selectivity. 

The influence of pH on the affinity of Hb for oxygen known as the Bohr-effect indicates that protons retain the allosteric regulation of oxygen transport. It is also an indirect confirmation of the ability of Hb and Im Hb for transporting carbon dioxide. The values of the Bohr-effect d log P50/d pH for Hb and Im Hb are close to each other in the pH range 7.1-7.4. It is possible that the effect of the micro-environment of carboxylic CP on immobilized Hb and its polyfunctional interaction represents the interaction between Hb and the structural elements inside the red cell [99]. 

The first pharmacological agent shown to activate AMPK was 5-aminoimidazole-4-carboxamide (AICA) riboside, also known as acadesine. This adenosine analogue is taken up into cells by adenosine transporters and phosphoiylated by adenosine kinase to the mono-phosphorylated form, AICA ribotide or ZMP. ZMP accumulates inside cells to higher concentrations than the concentration of AICA riboside present in the medium, and it mimics both effects of AMP on AMPK system (allosteric activation and inhibition of... 

Absorption of purines and pyrimidines by cestodes occurs by a combination of passive diffusion and mediated transport. In H. diminuta, purine and pyrimidine uptake is very complex and seems to involve at least three carrier systems (Table 6.9), two of which appear to bind several substrate molecules simultaneously (631). Pyrimidine transport was thought to involve allosteric regulation because the relation between initial uptake and substrate concentration was sigmoidal. However, more recent work (890) has indicated that the sigmoidal kinetics of pyrimidine transport in H. diminuta is an isotope effect, obtained only when 2-14C-labelled pyrimidines were used absorption kinetics of methyl-l4C- and 3H-labelled pyrimidines were hyperbolic. Nucleosides (thymidine, uridine, adenosine and guanosine) are absorbed by H. diminuta, H. citelli and H. microstoma via a specific sodium-dependent, mediated system involving at least two carriers (347). Interestingly, the mechanism displays a diurnal periodicity in H. diminuta (616, 617). 

Uglem, G. L., Dupre, R. K. Harley, J. P. (1983). Allosteric control of pyrimidine transport in Hymenolepis diminuta an unusual kinetic isotope effect. Parasitology, 87 289-93. 

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