M.S. (Master of Science)
Department of Chemistry
Anesthetics--Physiological effect; Microsomes; Cytochrome b₅; Enzymes; Local anesthesia
In the course of this work, the effects of local anesthetics were studied on the microsomal NADH-Fe(CN)₆³⁻ oxidoreductase and NADH-cytochrome c oxidoreductase activities as functions of both temperature and anesthetic concentration. The anesthetic agents used were tetracaine, procaine, dibucaine, n-butanol, n-pentanol, and benzyl alcohol. It was observed for both the intact microsomes and the water soluble lipid-free cytochrome b₅ reductase headgroups that the NADH-Fe(CN)₆³⁻ oxidoreductase activity decreased as a function of increasing anesthetic concentration at 30°C. The NADH-cytochrome c oxidoreductase activity was stimulated at low anesthetic concentrations, but was inhibited at higher concentrations at the same temperature. Since NADH-Fe(CN)₆³⁻ oxidoreductase activity depends on the presence of only membrane bound cytochrome b₅ reductase, the inhibition of this enzyme activity may be attributed to an anesthetic protein interaction and does not require the presence of the microsomal lipid bilayer. Because the NADH-cytochrome c oxidoreductase activity depends on lateral diffusion between cytochrome b₅ reductase and cytochrome b₅, the activation at low concentrations may be attributed to the fluidization of the lipid bilayer, induced by an anesthetic lipid interaction. The inhibition of this enzyme activity at higher concentrations may be attributed to an anesthetic protein interaction. It was also observed that a linear correlation existed between the inhibitory potencies of the anesthetic agents required for 50% inhibition and their oil/water partition coefficients. This suggests that hydrophobic interactions may be of importance in the inhibitory reactions.
Cokic, Peter, "Anesthetic activation and inhibition of the microsomal cytochrome b₅ reductase system" (1981). Graduate Research Theses & Dissertations. 1479.
v, 70 pages
Northern Illinois University
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