Mechanism of the biphasic effect of ethylenediaminetetraacetate on lipid peroxidation in iron-supported and reconstituted enzymatic system.
The biphasic action of ethylenediaminetetraacetate (EDTA), depending on its concentration, on lipid peroxidation was examined in an iron-supported and reconstituted enzymatic system. In the presence of NADPH-cytochrome P450 reductase and NADPH, Fe(3+)-PPi or Fe(3+)-ADP, though not reducible in the absence of EDTA, was markedly reduced with increasing concentration of EDTA. Lipid peroxidation, in the reconstituted system containing negatively charged liposomes, showed the maximal rate at 0.5 molar ratio of EDTA/iron, but no peroxidation occurred in positively charged liposomes, suggesting production of a positively charged iron complex as the prooxidant. Isotachophoresis indicated production of net-negative charge, EDTA-Fe(3+)-PPi complex, from Fe(3+)-PPi and EDTA at 1.1 ratio of EDTA/iron. The complex quenched Fe(2+)-PPi-supported lipid peroxidation. We suggest that EDTA-iron complexes of different charges are generated, depending on the amount of EDTA in the enzymatic system and, consequently, there is a switch between prooxidant and inhibitory effect at some critical ratio of EDTA/iron.
Division of Environmental Hygiene, Hokkaido Institute of Pharmaceutical Sciences, Otaru, Japan.
Y
Y
Tampo
S
S
Onodera
M
M
Yonaha
D000818:Animals; D004492:Edetic Acid / Q000494:pharmacology*; D005296:Ferrous Compounds / Q000494:pharmacology*; D007501:Iron / Q000494:pharmacology*; D007700:Kinetics; D015227:Lipid Peroxidation / Q000187:drug effects*; D008862:Microsomes, Liver / Q000201:enzymology*; D009249:NADP / Q000378:metabolism; D009251:NADPH-Ferrihemoprotein Reductase / Q000378:metabolism*; D010084:Oxidation-Reduction; D051381:Rats; D013997:Time Factors
D005296:Ferrous Compounds; C055526:Fe(II)-EDTA; D009249:NADP; D004492:Edetic Acid; D007501:Iron; D009251:NADPH-Ferrihemoprotein Reductase