A conformational model of the action of general anesthetics at the membrane level. III. Anesthetics and the properties of membrane-bound enzymes: mitochondrial ATPase.
We have studied the effect of general anesthetics on the kinetic properties of the mitochondrial Mg2+-dependent ATPase. The enzyme is inhibited by anesthetics (alcohols, halotane, pentrane, ketamine) at concentrations of the order of those found to affect lipid-protein interactions. The inhibition appears usually uncompetitive with respect to the substrate, ATP, with a decrease of both Vmax and KM, indicating a possible stabilization of the enzyme-substrate complex. Arrhenius plots of ATPase activity show a striking increase in activation energy below 17-20 degrees C. Anesthetics affect the temperature dependence by increasing the activation energy above the break or abolishing the break whatsoever. An exception is diethyl ether, that induces a decrease in activation energy and a shift of the break to lower temperatures. Anesthetics make the ATPase insensitive to energy transfer inhibitor, oligomycin and dicyclohexyl carbodiimide. At low anesthetic concentration the oligomycin inhibition curve is changed from sigmoidal to hyperbolic, showing a loss of cooperativity in the inhibition.
D000251:Adenosine Triphosphatases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D000768:Anesthesia, General; D000777:Anesthetics / Q000494:pharmacology*; D000818:Animals; D001665:Binding Sites / Q000187:drug effects; D002417:Cattle; D003124:Colorimetry; D004024:Dicyclohexylcarbodiimide / Q000494:pharmacology; D006801:Humans; D008560:Membrane Fluidity / Q000187:drug effects; D008563:Membrane Lipids / Q000378:metabolism; D008565:Membrane Proteins / Q000378:metabolism; D008566:Membranes / Q000187:drug effects* / Q000201:enzymology; D008929:Mitochondria, Heart / Q000201:enzymology; D008954:Models, Biological; D009840:Oligomycins / Q000494:pharmacology; D013696:Temperature
D000777:Anesthetics; D008563:Membrane Lipids; D008565:Membrane Proteins; D009840:Oligomycins; D004024:Dicyclohexylcarbodiimide; D000251:Adenosine Triphosphatases