Rat pulmonary lipoxygenase: dioxygenase activity and role in xenobiotic metabolism.
1. Dioxygenase activity and the ability of pregnant rat lung lipoxygenase to oxidize xenobiotics were examined in vitro under a variety of experimental conditions. 2. More than 90% of the dioxygenase activity towards linoleic acid in the lung homogenate was found to be associated with the cytosolic fraction. The cytosolic enzyme exhibited pH optima at 6.5 and 9.5, the activity being two-fold greater at pH 9.5. To observe maximal dioxygenase activity (about 0.7 mumol of 13-hydroperoxylinoleic acid formed/min per mg protein) at pH 9.5, the presence of 6.0 mM linoleic acid was required. 3. Benzidine oxidation occurred at maximal rate of pH 6.5 when the reaction medium contained 1.0 mM benzidine and 13.5 mM linoleic acid. All eight xenobiotics tested were oxidized at significant rates by the lung cytosolic lipoxygenase. 4. Both dioxygenase activity and benzidine oxidation were inhibited by the inhibitors of lipoxygenase, viz. nordihydroguaiaretic acid, BHT, caffeic acid, esculetin, and gossypol, in a concentration-dependent manner. 5. The results suggest that oxidation of xenobiotics by lipoxygenase may be an important pathway of metabolism in the mammalian lung.
Kulkarni
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Department of Environmental and Occupational Health, College of Public Health, University of South Florida, Tampa 33612.
Cai
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Richards
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D000818:Animals; D005260:Female; D008041:Linoleic Acids / Q000378:metabolism; D008084:Lipoxygenase / Q000378:metabolism*; D016859:Lipoxygenase Inhibitors / Q000494:pharmacology; D008168:Lung / Q000201:enzymology*; D010084:Oxidation-Reduction; D011247:Pregnancy; D051381:Rats; D011919:Rats, Inbred Strains; D013379:Substrate Specificity; D015262:Xenobiotics / Q000378:metabolism*
D008041:Linoleic Acids; D016859:Lipoxygenase Inhibitors; D015262:Xenobiotics; D008084:Lipoxygenase