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Effect of Zinc and Copper Deficiency on Microsomal NADPH-Dependent Active Oxygen Generation in Rat Lung and Liver^1,2,

Department of Nutritional Sciences, College of Biological Science, University of Guelph, Guelph, Ontario, Canada N1G 2W1

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 copper deficiency causes microsomal lipid peroxidation is still unknown but could be related to the observed accumulation of iron.

KEY WORDS: • zinc • copper • iron • microsomes • active oxygen • cytochrome P-450 • lung • liver

¹ This work is supported by National Heart, Lung and Blood Institute Grant No. HL33491-01.

² Presented in part at the 1986 Annual Meeting of the Federation of American Societies for Experimental Biology, St. Louis, MO, April 13–18. HAMMERMUELLER, J. D., BRAY, T. M. & BETTGER, W. J. (1986) Effect of zinc deficiency on NADPH and cyt. P-450 dependent active oxygen generation in rat lung and liver. Fed. Proc. 45: 1083 (abs.). Also presented in part at the 29th Annual Meeting of the Canadian Federation of Biological Societies, University of Guelph, Guelph, Ontario, Canada, June 1986. HAMMERMUELLER, J. D., BETTGER, W. J. & BRAY, T. M. (1986) The effect of zinc/copper deficiency on microsomal NADPH-dependent active oxygen generation in rat lung and liver. Can. Fed. Biol. Soc. Proc. 29: 103 (abs.).

Manuscript received 13 August 1986. Revision accepted 23 January 1987.

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