Inhibition of cytochrome oxidase by dibucaine.
Dibucaine-HCl inhibited mitochondrial cytochrome c oxidase activity in intact mitochondria with 50% inhibition occurring at 1.1 mM dibucaine-HCl. Dibucaine-HCl did not prevent the reduction of cytochrome oxidase by ascorbate plus N,N,N',N'-tetramethyl-p-phenylenediamine dihydrochloride (TMPD) when measured at 604 nm but prevented 50% of the absorbance change at 445 nm; dithionite reduced the oxidase completely. Dibucaine prevented binding of CO to oxidase reduced with ascorbate plus TMPD by preventing the reduction of cytochrome a3. The midpotenials of cytochrome c and cytochrome oxidase, the visible absorbance wavelength maxima, and the position and intensity of the signals of the EPR spectrum of the oxidase were not affected. Dibucaine-HCl prevented ascorbate plus TMPD-driven reduction of the near infra-red detectable copper center associated with cytochrome a: dithionite subsequently reduced this center. Dibucaine-HCl inhibited cytochrome oxidase activity by interacting between cytochrome a and its associated copper. Since respiration was 8-fold less sensitive in submitochondrial particles, this site of inhibition is on the cytoplasmic side of the membrane.
Stringer
B K
BK
Department of Zoology, Oklahoma State University, Stillwater 74078.
Harmon
H J
HJ
D000818:Animals; D002417:Cattle; D003992:Dibucaine / Q000494:pharmacology*; D003576:Electron Transport Complex IV / Q000037:antagonists & inhibitors*; D008929:Mitochondria, Heart / Q000187:drug effects / Q000201:enzymology*; D010084:Oxidation-Reduction; D010088:Oxidoreductases / Q000378:metabolism; D013772:Tetramethylphenylenediamine / Q000494:pharmacology
D010088:Oxidoreductases; C022691:succinate oxidase; D003576:Electron Transport Complex IV; D003992:Dibucaine; D013772:Tetramethylphenylenediamine