INHALATION ANAESTHETICS AND THEIR INTERACTION IN VITRO WITH GLUTAMATE DEHYDROGENASE AND OTHER ENZYMES

Several enzymes of the Embden-Myerhof pathway were found, in vitro, to be insensitive to high concentrations of halothane. However, glutamate dehydrogenase was inhibited in vitro in a dose-dependent manner by methoxyflurane, trichloroethylene, diethyl ether and halothane in concentrations greater than those used in clinical practice. This allosteric enzyme is believed to be involved with central nervous transmission. The inhibition of activity was immediate and reversible with all the agents investigated. In the presence of halothane, enzyme kinetic experiments demonstrated that the inhibition was of the non-competitive type thus suggesting that anaesthetic agents induced conformational changes in the glutamate dehydrogenase molecule.