Xenon, laughing gas and cytochrome P450: Spectroscopic studies of inhaled anesthetics and their putative targets

PHYS 405

Amy F. Grimes, grimesa2@mail.nih.gov, Laboratory of Molecular Biophysics, National Heart, Lung and Blood Institute, National Institutes of Health, 9000 Rockville Pike, Bethesda, MD 20892-8013 and Jennifer C. Lee, leej4@mail.nih.gov, Laboratory of Molecular Biophysics, National Heart, Lung, and Blood Institute, National Institutes of Health, 9000 Rockville Pike, National Institutes of Health, Bethesda, MD 20892.
Despite the prevalent use of inhaled anesthetics, their mechanism and site of action remain poorly understood. In eukaryotes, the heme enzyme cytochrome P450 produces eicosanoids critical to cellular messaging in the central nervous system. Disruption of eicosanoid production is a potential basis for anesthetic action. In addition, the deeply buried heme appears to be accessible to and perturbed by anesthetic molecules at clinically relevant concentrations. Cytochrome P450-BM3 is used as a soluble model system for membrane bound eukaryotic cytochrome P450s due to their high primary sequence homology. Spectroscopic assays aim to elucidate the effects of nitrous oxide and xenon on the activity of P450-BM3. Fluorescence techniques will be used to observe the substrate channel dynamics induced by substrate binding and determine how the presence of anesthetic gases modulates this process.
 

PHYS Poster Session - General Experiment
7:30 PM-10:00 PM, Wednesday, April 9, 2008 Morial Convention Center -- Hall A, Poster

Sci-Mix
8:00 PM-10:00 PM, Monday, April 7, 2008 Morial Convention Center -- Hall A, Sci-Mix

Division of Physical Chemistry

The 235th ACS National Meeting, New Orleans, LA, April 6-10, 2008