Studies of ascorbate-dependent, iron-catalyzed lipid peroxidation.
We have previously observed that both Fe(II) and Fe(III) are required for lipid peroxidation to occur, with maximal rates of lipid peroxidation observed when the ratio of Fe(II) to Fe(III) is approximately one (J. R. Bucher et al. (1983) Biochem. Biophys. Res. Commun. 111, 777-784; G. Minotti and S. D. Aust (1987) J. Biol. Chem. 262, 1098-1104). Consistent with the requirement for both Fe(II) and Fe(III), ascorbate, by reducing Fe(III) to Fe(II), stimulated iron-catalyzed lipid peroxidation but when the ascorbate concentration was sufficient to reduce all of the Fe(III) to Fe(II), ascorbate inhibited lipid peroxidation. The rates of lipid peroxidation were unaffected by the addition of catalase, superoxide dismutase, or hydroxyl radical scavengers. Exogenously added H2O2 also either stimulated or inhibited ascorbate-dependent, iron-catalyzed lipid peroxidation apparently by altering the ratio of Fe(II) to Fe(III). Thus, it appears that the prooxidant effect of ascorbate is related to the ability of ascorbate to promote the formation of a proposed Fe(II):Fe(III) complex and not due to oxygen radical production. The antioxidant effect of ascorbate on iron-catalyzed lipid peroxidation may be due to complete reduction of iron.
Miller
D M
DM
Department of Chemistry and Biochemistry, Utah State University, Logan 84322-4430.
Aust
S D
SD
D000818:Animals; D001205:Ascorbic Acid / Q000494:pharmacology*; D002384:Catalysis; D005290:Ferric Compounds / Q000494:pharmacology; D005296:Ferrous Compounds / Q000494:pharmacology; D006861:Hydrogen Peroxide / Q000494:pharmacology; D007501:Iron / Q000494:pharmacology*; D007502:Iron Chelating Agents / Q000378:metabolism; D008054:Lipid Peroxides / Q000096:biosynthesis*; D008862:Microsomes, Liver / Q000187:drug effects / Q000378:metabolism*; D010084:Oxidation-Reduction; D051381:Rats
D005290:Ferric Compounds; D005296:Ferrous Compounds; D007502:Iron Chelating Agents; D008054:Lipid Peroxides; D006861:Hydrogen Peroxide; D007501:Iron; D001205:Ascorbic Acid