Studies of the ferroxidase activity of native and chemically modified xanthine oxidoreductase.
The O2-utilizing (type O, oxidase) form of xanthine oxidoreductase is primarily responsible for its ferroxidase activity. This form of xanthine oxidoreductase has 1000 times the ferroxidase activity of the serum ferroxidase caeruloplasmin. It has the ability to catalyse the oxidative incorporation of iron into transferrin at very low Fe2+ and O2 concentrations. Furthermore, the pH optimum of the ferroxidase activity of the enzyme is compatible with the conditions of pH that normally exist in the intestinal mucosa, where it has been proposed that xanthine oxidoreductase may facilitate the absorption of ionic iron. Modification of the molybdenum (Mb) centres of the enzyme in vitro by treatment with cyanide, methanol or allopurinol completely abolishes its ferroxidase activity. The feeding of dietary tungsten to rats, which prevents the incorporation of molybdenum into newly synthesized intestinal xanthine oxidoreductase, results in the progressive loss of the ferroxidase activity of intestinal-mucosa homogenates. Removal of the flavin centres from the enzyme also results in the complete loss of ferroxidase activity; however, the ferroxidase activity of the flavin-free form of the enzyme can be restored with artificial electron acceptors that interact with the molybdenum or non-haem iron centres. The presence of superoxide dismutase or catalase in the assay system results in little inhibition of the ferroxidase activity of xanthine oxidoreductase.
D000818:Animals; D002570:Ceruloplasmin / Q000378:metabolism; D055598:Chemical Phenomena; D002621:Chemistry; D005260:Female; D007413:Intestinal Mucosa / Q000187:drug effects / Q000201:enzymology; D007527:Isoenzymes / Q000378:metabolism*; D007700:Kinetics; D008982:Molybdenum / Q000378:metabolism; D010100:Oxygen / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D014414:Tungsten / Q000494:pharmacology; D014969:Xanthine Oxidase / Q000378:metabolism*
D007527:Isoenzymes; D008982:Molybdenum; D002570:Ceruloplasmin; D014969:Xanthine Oxidase; D010100:Oxygen; D014414:Tungsten