A hydrogen-donating monohydroxamate scavenges ferryl myoglobin radicals
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A hydrogen-donating monohydroxamate scavenges ferryl myoglobin radicals. / Cooper, C E; Green, E S; Rice-Evans, C A; Davies, M J; Wrigglesworth, J M.
In: Free Radical Research, Vol. 20, No. 4, 04.1994, p. 219-27.Research output: Contribution to journal › Journal article › Research › peer-review
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T1 - A hydrogen-donating monohydroxamate scavenges ferryl myoglobin radicals
AU - Cooper, C E
AU - Green, E S
AU - Rice-Evans, C A
AU - Davies, M J
AU - Wrigglesworth, J M
PY - 1994/4
Y1 - 1994/4
N2 - The addition of 25 microM hydrogen peroxide to 20 microM metmyoglobin produces ferryl (FeIV = O) myoglobin. Optical spectroscopy shows that the ferryl species reaches a maximum concentration (60-70% of total haem) after 10 minutes and decays slowly (hours). Low temperature EPR spectroscopy of the high spin metmyoglobin (g = 6) signal is consistent with these findings. At this low peroxide concentration there is no evidence for iron release from the haem. At least two free radicals are detectable by EPR immediately after H2O2 addition, but decay completely after ten minutes. However, a longer-lived radical is observed at lower concentrations that is still present after 90 minutes. The monohydroxamate N-methylbutyro-hydroxamic acid (NMBH) increases the rate of decay of the fenyl species. In the presence of NMBH, none of the protein-bound free radicals are detectable; instead nitroxide radicals produced by oxidation of the hydroxamate group are observed. Similar results are observed with the trihydroxamate, desferrioxamine. "Ferryl myoglobin" is still able to initiate lipid peroxidation even after the short-lived protein free radicals are no longer detectable (E.S.R. Newman, C.A. Rice-Evans and M.J. Davies (1991) Biochemical and Biophysical Research Communications 179, 1414-1419). It is suggested that the longer-lived protein radicals described here may be partly responsible for this effect. The mechanism of inhibition of initiation of lipid peroxidation by hydroxyamate drugs, such as NMBH, may therefore be due to reduction of the protein-derived radicals, rather than reduction of ferryl haem.
AB - The addition of 25 microM hydrogen peroxide to 20 microM metmyoglobin produces ferryl (FeIV = O) myoglobin. Optical spectroscopy shows that the ferryl species reaches a maximum concentration (60-70% of total haem) after 10 minutes and decays slowly (hours). Low temperature EPR spectroscopy of the high spin metmyoglobin (g = 6) signal is consistent with these findings. At this low peroxide concentration there is no evidence for iron release from the haem. At least two free radicals are detectable by EPR immediately after H2O2 addition, but decay completely after ten minutes. However, a longer-lived radical is observed at lower concentrations that is still present after 90 minutes. The monohydroxamate N-methylbutyro-hydroxamic acid (NMBH) increases the rate of decay of the fenyl species. In the presence of NMBH, none of the protein-bound free radicals are detectable; instead nitroxide radicals produced by oxidation of the hydroxamate group are observed. Similar results are observed with the trihydroxamate, desferrioxamine. "Ferryl myoglobin" is still able to initiate lipid peroxidation even after the short-lived protein free radicals are no longer detectable (E.S.R. Newman, C.A. Rice-Evans and M.J. Davies (1991) Biochemical and Biophysical Research Communications 179, 1414-1419). It is suggested that the longer-lived protein radicals described here may be partly responsible for this effect. The mechanism of inhibition of initiation of lipid peroxidation by hydroxyamate drugs, such as NMBH, may therefore be due to reduction of the protein-derived radicals, rather than reduction of ferryl haem.
KW - Animals
KW - Deferoxamine
KW - Electron Spin Resonance Spectroscopy
KW - Free Radical Scavengers
KW - Horses
KW - Hydrogen Peroxide
KW - Hydroxamic Acids
KW - Metmyoglobin
M3 - Journal article
C2 - 8205224
VL - 20
SP - 219
EP - 227
JO - Free Radical Research
JF - Free Radical Research
SN - 1071-5762
IS - 4
ER -
ID: 152246943