Nerve cell excitation is probably a function assigned to membrane proteins embedded into lipid bilayers. Despite the general contention that the final target of anesthetic actions may be proteins, the effect is often considered to be secondary to the change in the solvent property of supporting lipid bilayers. Nevertheless, there is evidence of direct protein-anesthetic interaction. Probably the most conclusive is the inhibition of lipid-free light emitting enzymes by inhalation anesthetics. We propose that actions of inhalation anesthetics are directed to macro-molecule-water interfaces, affecting lipids and proteins indiscriminately. This project aims at elucidation of direct interactions between proteins and inhalation anesthetics. anesthetic interactions with lipid membranes will be investigated in a separate project. Macromolecular structure, regardless of whether they are proteins or lipid membranes, are supported by interaction forces between macromolecules and the hydrogen-bonded matrix of water molecules. Anything that weakens this interaction induces disorder in the macromolecular structure. We hypothesize that the primary action of anesthetics is to weaken macromolecule-water interaction. In this context, anesthetics are not a membrane stabilizer but a destabilizer. To provide or disprove this hypothesis, anesthetic effects upon interfacial properties of macromolecules are examined. Our previous project was mainly composed of model macromolecules. There is an obvious need to compare the change in physical properties with protein functions. For this reason, we include light emitting enzymes, where functions can be conveniently analyzed by measuring the light intensity. Methods of estimating macro-melecular physical properties consist of standard colloid and interface chemistry procedures that have been successfully used in previous funding periods.
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