Sevoflurane modulates the activity of glyceraldehyde 3-phosphate dehydrogenase.
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.
Swearengin
Timothy A
TA
Department of Anesthesiology, University of Missouri, Kansas City School of Medicine, 4401 Wornall Road, Kansas City, MO, USA.
Fibuch
Eugene E
EE
Seidler
Norbert W
NW
D000818:Animals; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D006801:Humans; D008738:Methyl Ethers / Q000737:chemistry / Q000494:pharmacology*; D015394:Molecular Structure; D009132:Muscles / Q000187:drug effects / Q000201:enzymology; D009243:NAD / Q000494:pharmacology; D011489:Protein Denaturation; D011817:Rabbits; D000077149:Sevoflurane; D013050:Spectrometry, Fluorescence; D013696:Temperature
D004791:Enzyme Inhibitors; D008738:Methyl Ethers; D009243:NAD; D000077149:Sevoflurane; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases