Effect of zinc and copper deficiency on microsomal NADPH-dependent active oxygen generation in rat lung and liver.
Both dietary zinc and copper deficiencies can cause lipid peroxidation in microsomes in rats. The cytochrome P-450 enzyme system can generate active oxygens by uncoupling of the P-450-oxy complex in the catalytic cycle and/or the electron transfer mediated by the NADPH-cytochrome P-450 reductase. The effects of dietary zinc and copper deficiencies on NADPH-dependent H2O2 generation, the catalytic activity of the cytochrome P-450 enzyme with aminopyrine as the substrate and the activity of NADPH-cytochrome P-450 reductase were determined. Zinc deficiency caused increased H2O2 production, increased NADPH-cytochrome P-450 reductase activity, decreased aminopyrine demethylation and two- and fivefold increases in iron concentration in lung and liver microsomes, respectively, compared to Zn-adequate, ad libitum--fed controls. Active oxygen generation by uncoupling of the cytochrome P-450 enzyme system and accumulation of iron are thus possible mechanisms by which zinc deficiency causes microsomal lipid peroxidation. Copper deficiency did not affect H2O2 production; however, it caused two- and fourfold increases in iron concentration in lung and liver microsomes, respectively, compared to Cu-adequate, ad libitum--fed controls. The mechanism by which cooper deficiency causes microsomal lipid peroxidation is still unknown but could be related to the observed accumulation of iron.
D000818:Animals; D003300:Copper / Q000172:deficiency*; D004032:Diet; D005260:Female; D006861:Hydrogen Peroxide / Q000378:metabolism; D008054:Lipid Peroxides / Q000378:metabolism; D008168:Lung / Q000201:enzymology*; D008297:Male; D008862:Microsomes, Liver / Q000201:enzymology*; D009247:NADH, NADPH Oxidoreductases / Q000378:metabolism*; D009252:NADPH Dehydrogenase / Q000378:metabolism*; D011247:Pregnancy; D051381:Rats; D011919:Rats, Inbred Strains; D015032:Zinc / Q000172:deficiency*
D008054:Lipid Peroxides; D003300:Copper; D006861:Hydrogen Peroxide; D009247:NADH, NADPH Oxidoreductases; D009252:NADPH Dehydrogenase; D015032:Zinc