Desferrioxamine (Desferal) and superoxide free radicals. Formation of an enzyme-damaging nitroxide.
In neutral solutions, desferrioxamine (Desferal) can react with the superoxide free radical, O2.- (possibly through its protonated form HO2.), to form a relatively stable nitroxide free radical, which can have a half-life of approx. 10 min at room temperature. The formation of the radical can be largely prevented by the presence of superoxide dismutase. The radical reacts rapidly with cysteine, methionine, glutathione, vitamin C and a water-soluble derivative of vitamin E. It also reacts rapidly with alcohol dehydrogenase, causing a loss of enzyme activity. The implications of these findings for mechanistic free-radical biochemistry and iron-chelation therapy could be considerable.
Davies
M J
MJ
Department of Biochemistry, Brunel University, Uxbridge, Middx., U.K.
Donkor
R
R
Dunster
C A
CA
Gee
C A
CA
Jonas
S
S
Willson
R L
RL
D000426:Alcohol Dehydrogenase / Q000037:antagonists & inhibitors; D000975:Antioxidants / Q000494:pharmacology; D003676:Deferoxamine / Q000494:pharmacology*; D004578:Electron Spin Resonance Spectroscopy; D005609:Free Radicals; D009589:Nitrogen Oxides / Q000378:metabolism*; D013481:Superoxides / Q000378:metabolism*
D000975:Antioxidants; D005609:Free Radicals; D009589:Nitrogen Oxides; D013481:Superoxides; D000426:Alcohol Dehydrogenase; D003676:Deferoxamine