A microsomal membrane component associated with iron reduction in NADPH-supported lipid peroxidation.
This study was conducted to determine whether a factor responsible for reduced nicotinamide adenine dinucleotide phosphate (NADPH)-supported lipid peroxidation in rat liver microsomes is involved in iron reduction by cooperation with NADPH-cytochrome P450 reductase. Under anaerobic conditions, NADPH-dependent reduction of ferric pyrophosphate in microsomes was not dependent on cytochrome P450 levels and was not inhibited by carbon monoxide (CO). All of the iron complexes with chelators such as adenosine 5'-diphosphate, pyrophosphate, nitrilotriacetate, oxalate or citrate were reduced in microsomes, although in the reconstituted system containing purified NADPH-cytochrome P450 reductase little or no iron reduction was found. A cytochrome P450-free fraction from a cholate-solubilized preparation of microsomes after passage through a laurate sepharose column was required for reduction of iron pyrophosphate in the reconstituted system leading to lipid peroxidation. The iron reduction was not inhibited by CO and was destroyed by heat treatment or trypsin digestion of the fraction. All iron complexes were reduced in the presence of the fraction, using a reducing equivalent of NADPH via NADPH-cytochrome P450 reductase. The results indicate that a heat-labile component, which is probably a protein distinct from cytochrome P450, is associated with iron reduction responsible for lipid peroxidation in microsomes.
Tampo
Y
Y
Division of Environmental Hygiene, Hokkaido Institute of Pharmaceutical Sciences, Otaru, Japan.
Yonaha
M
M
D000818:Animals; D019826:Cholic Acid; D002793:Cholic Acids; D002847:Chromatography, Agarose; D003577:Cytochrome P-450 Enzyme System / Q000302:isolation & purification; D007425:Intracellular Membranes / Q000502:physiology*; D007501:Iron / Q000378:metabolism*; D015227:Lipid Peroxidation / Q000502:physiology*; D008297:Male; D008862:Microsomes, Liver / Q000502:physiology*; D009249:NADP / Q000502:physiology*; D009251:NADPH-Ferrihemoprotein Reductase / Q000378:metabolism*; D010084:Oxidation-Reduction; D051381:Rats; D017207:Rats, Sprague-Dawley; D012995:Solubility
D002793:Cholic Acids; D009249:NADP; D003577:Cytochrome P-450 Enzyme System; D007501:Iron; D009251:NADPH-Ferrihemoprotein Reductase; D019826:Cholic Acid