Sevoflurane Modulates the Activity of Glyceraldehyde 3-Phosphate Dehydrogenase
Document Type
Article
Publication Title
Journal of Enzyme Inhibition and Medicinal Chemistry
Abstract
The mechanism of inhalation anesthesia remains to be fully elucidated. While certain neuronal membrane proteins are considered sites of action, cytosolic proteins may also be targets. We hypothesize that inhaled anesthetics may act via glyceraldehyde 3-phosphate dehydrogenase (GAPDH), which has recently been shown to participate in neuronal inhibition. We examined the effects of sevoflurane, a halogenated ether anesthetic, on the catalytic and fluorescence properties of GAPDH. Initial rates of oxidoreductase activity decreased approximately 30% at saturating levels of sevoflurane. NADH-stimulated oxidoreductase activity (25 microM NADH; 0.8mM NAD+) increased with sevoflurane. Sevoflurane quenched tryptophan fluorescence emission and increased polarization. Additionally, sevoflurane increased the susceptibility of GAPDH to thermal denaturation suggesting an effect on conformation. Our findings warrant further research on sevoflurane's effect on GAPDH and indicate that this approach may lead to delineation of a novel contribution to the mechanism of anesthesia.
DOI
10.1080/14756360600741925
Publication Date
10-2006
Keywords
Sevoflurane, glyceraldehyde 3-phosphate dehydrogenase, intrinsic fluorescence, inhibition
ISSN
1475-6374
Recommended Citation
Swearengin T, Fibuch EE, Seidler NW. Sevoflurane Modulates the Activity of Glyceraldehyde 3-Phosphate Dehydrogenase. Journal of Enzyme Inhibition and Medicinal Chemistry. 2006; 21(5). doi: 10.1080/14756360600741925.
