The site of general anesthesia and cytochrome P450 monooxygenases: occupation of the enzyme heme pocket by xenon and nitrous oxide.
In previous studies, cytochrome P450 monooxygenases were shown to be appropriately sensitive to structurally diverse compounds varying widely in anesthetic potencies and to increasing carbon-number series of straight chain primary and secondary alcohols and rigid cyclic alcohols. We now report that xenon and nitrous oxide, at one atmosphere, occupy the P450 heme cavity and competitively inhibit catalytic activity. The heme enzymes appear to be the most relevant model of the site of general anesthesia, thus far identified.
LaBella
F S
FS
Department of Pharmacology and Therapeutics, Faculty of Medicine, University of Manitoba, 753 McDermot Avenue, Winnipeg, Manitoba, Canada. labellaf@ms.umanitoba.ca
Stein
D
D
Queen
G
G
D018681:Anesthetics, General / Q000378:metabolism* / Q000494:pharmacology; D000818:Animals; D001665:Binding Sites; D001667:Binding, Competitive; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D006420:Hemeproteins / Q000187:drug effects / Q000378:metabolism; D008862:Microsomes, Liver / Q000187:drug effects / Q000378:metabolism; D009609:Nitrous Oxide / Q000378:metabolism / Q000494:pharmacology; D011485:Protein Binding; D051381:Rats; D014978:Xenon / Q000378:metabolism / Q000494:pharmacology
D018681:Anesthetics, General; D006420:Hemeproteins; D014978:Xenon; D003577:Cytochrome P-450 Enzyme System; D009609:Nitrous Oxide