The site of general anesthesia and cytochrome P450 monooxygenases: occupation of the enzyme heme pocket by xenon and nitrous oxide

LaBella, Frank S.; Stein, Douglas; Queen, Gary

doi:10.1016/s0014-2999(99)00553-1

Cited by 12 publications

(8 citation statements)

References 8 publications

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“…An important representative of HRgY molecules is HXeOH, formed from H 2 O and Xe as described elsewhere. , It was suggested that HXeOH could be found in aqueous global surroundings, which establishes a high value for studies of HXeOH in water clusters. This consideration is relevant to the known attempts to solve the geochemical “missing Xe” problem, and it might also be connected with understanding the anesthetic properties of Xe …”

Section: Introductionmentioning

confidence: 99%

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Intermolecular Complexes of HXeOH with Water: Stabilization and Destabilization Effects

et al. 2002

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Theoretical and matrix-isolation studies of intermolecular complexes of HXeOH with water molecules are presented. The structures and possible decomposition routes of the HXeOH-(H(2)O)(n)(n = 0, 1, 2, 3) complexes are analyzed theoretically. It is concluded that the decay of these metastable species may proceed through the bent transition states (TSs), leading to the global minima on the respective potential energy surfaces, Xe + (H(2)O)(n+1). The respective barrier heights are 39.6, 26.6, 11.2, and 0.4 kcal/mol for n = 0, 1, 2, and 3. HXeOH in larger water clusters is computationally unstable with respect to the bending coordinate, representing the destabilization effect. Another decomposition channel of HXeOH-(H(2)O)(n), via a linear TS, leads to a direct break of the H-Xe bond of HXeOH. In this case, the attached water molecules stabilize HXeOH by strengthening the H-Xe bond. Due to the stabilization, a large blue shift of the H-Xe stretching mode upon complexation of HXeOH with water molecules is featured in calculations. On the basis of this computational result, the IR absorption bands at 1681 and 1742 cm(-1) observed after UV photolysis and annealing of multimeric H(2)O/Xe matrixes are assigned to the HXeOH-H(2)O and HXeOH-(H(2)O)(2) complexes. These bands are blue-shifted by 103 and 164 cm(-1) from the known monomeric HXeOH absorption.

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Section: Introductionmentioning

confidence: 99%

“…This consideration is relevant to the known attempts to solve the geochemical "missing Xe" problem, 12 and it might also be connected with understanding the anesthetic properties of Xe. 13 In this article, we study the complexation of HXeOH with water molecules. It is shown that HXeOH can form stable complexes with water molecules.…”

Section: Introductionmentioning

confidence: 99%

Intermolecular Complexes of HXeOH with Water: Stabilization and Destabilization Effects

et al. 2002

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“…Xenon is a noble gas element that has long been known to have anesthetic properties, mainly due to its ability to inhibit N ‐methyl‐ d ‐aspartate (NMDA) receptors in the brain . As xenon has a low ionization potential, its electron shell can be polarized by surrounding molecules, enabling it to act as an inhibitor in the active sites of proteins such as serine proteases . Xenon noncompetitive inhibition of the NMDA receptor is also responsible for the element's neuroprotective effects, in which Ca 2 + influx into neurons, inducing apoptotic mechanisms, is blocked …”

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confidence: 99%

“…[1,2] As xenon has a low ionization potential, its electron shell can be polarized by surrounding molecules, enabling it to act as an inhibitor in the active sites of proteins such as serine proteases. [3][4][5][6] Xenon noncompetitive inhibition of the NMDA receptor is also responsible for the element's neuroprotective effects, in which Ca 2+ influx into neurons, inducing apoptotic mechanisms, is blocked. [2,7] Numerous candidate neuroprotective agents have been tested for efficacy in acute ischemic stroke, but were shown to be ineffective in clinical trials.…”

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confidence: 99%

Gas chromatography/mass spectrometry measurement of xenon in gas‐loaded liposomes for neuroprotective applications

Klegerman

Moody

Hurling

et al. 2016

Rapid Comm Mass Spectrometry

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Rationale We have produced a liposomal formulation of xenon (Xe-ELIP) as a neuroprotectant for inhibition of brain damage in stroke patients. This mandates development of a reliable assay to measure the amount of dissolved xenon released from Xe-ELIP in water and blood samples. Methods Gas chromatography-Mass Spectrometry (GC-MS) was used to quantify xenon gas released into the headspace of vials containing Xe-ELIP samples in water or blood. In order to determine blood concentration of xenon in vivo after Xe-ELIP administration, 6 mg Xe-ELIP lipid was infused intravenously into rats. Blood samples were drawn directly from a catheterized right carotid artery. After introduction of the samples, each vial was allowed to equilibrate to 37° C in a water bath, followed by 20 minutes of sonication prior to headspace sampling. Xenon concentrations were calculated from a gas dose-response curve and normalized using the published xenon water-gas solubility coefficient. Results The mean corrected percent of xenon from Xe-ELIP released into water was 3.87 ± 0.56% (SD, n = 8), corresponding to 19.3 ± 2.8 μl/mg lipid, which is consistent with previous independent Xe-ELIP measurements. The corresponding xenon content of Xe-ELIP in rat blood was 23.38 ± 7.36 μl/mg lipid (n = 8). Mean rat blood xenon concentration after IV administration of Xe-ELIP was 14 ± 10 μM, which is approximately 15% of the estimated neuroprotective level. Conclusions Using this approach, we have established a reproducible method for measuring dissolved xenon in fluids. These measurements have established that neuroprotective effects can be elicited by less than 20% of the calculated neuroprotective xenon blood concentration. More work will have to be done to establish the protective xenon pharmacokinetic range.

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“…Under gas pressures ranging from 8 to 20 bar, xenon is able to bind to discrete sites in hydrophobic cavities, ligand-binding and substratebinding pockets and into the pore of channel-like structures. Xenon, through weak van der Waals forces, can bind to pre-existing atomicsized cavities in the interior of certain globular protein molecules (Schoenborn and Nobbs, 1966;Tilton et al 1986;Tilton et al 1988;Schiltz et al 1995;Prange et al 1998;Labella et al 1999). Xenon demonstrates an exceptional promiscuity, even binding to tissueplasminogen activator, which is a serine protease (David et al, 2010).…”

Section: Discussionmentioning

confidence: 99%

Xenon reduces activation of transient receptor potential vanilloid type 1 (TRPV1) in rat dorsal root ganglion cells and in human TRPV1-expressing HEK293 cells

et al. 2011

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The site of general anesthesia and cytochrome P450 monooxygenases: occupation of the enzyme heme pocket by xenon and nitrous oxide

Cited by 12 publications

References 8 publications

Intermolecular Complexes of HXeOH with Water: Stabilization and Destabilization Effects

Intermolecular Complexes of HXeOH with Water: Stabilization and Destabilization Effects

Gas chromatography/mass spectrometry measurement of xenon in gas‐loaded liposomes for neuroprotective applications

Xenon reduces activation of transient receptor potential vanilloid type 1 (TRPV1) in rat dorsal root ganglion cells and in human TRPV1-expressing HEK293 cells

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