Epoxide reductase activity of mammalian liver cytosols and aldehyde oxidase.
The present study provides the first evidence that a mammalian liver cytosolic enzyme, aldehyde oxidase, has an ability to reduce arene oxides to the parent hydrocarbons under anaerobic conditions. The comparative ability of rabbit liver preparations to reduce arene oxides was examined using naphthalene 1,2-oxide and benzo[a]pyrene 4,5-oxide as substrates. The liver cytosol with an electron donor of aldehyde oxidase exhibited much higher epoxide reductase activity compared with the liver microsomes with NADPH and FAD. The cytosolic activity was sensitive to inhibitors of aldehyde oxidase. Purified rabbit liver aldehyde oxidase also exhibited a significant epoxide reductase activity in the presence of its electron donor. Apparent Km and Vmax values of the enzyme were 426 microM and 323 nmol/min/mg protein for naphthalene 1,2-oxide and 255 microM and 100 nmol/min/mg protein for benzo[a]pyrene 4,5-oxide respectively. However, no epoxide reduction by the enzyme or by the liver cytosol was detected in olefin epoxides such as styrene oxide and trans-stilbene oxide. Similar results were obtained with rat liver preparations. However, the epoxide reductase activity of cytosol and aldehyde oxidase from rat liver was considerably lower than that of the rabbit liver preparations. In hamsters, mice and guinea-pigs, liver cytosols with an electron donor of aldehyde oxidase as well as liver microsomes with NADPH exhibited a significant epoxide reductase activity toward naphthalene 1,2-oxide. However, no epoxide reduction was observed with dog liver cytosol. Administration of sodium tungstate to rats depleted liver cytosolic reductase activity and sodium molybdate treatment resulted in partial restoration of the activity, supporting the view that the epoxide reductase activity observed in the liver cytosol mainly originates from aldehyde oxidase.
Hirao
Y
Y
Institute of Pharmaceutical Science, Hiroshima University, School of Medicine, Japan.
Kitamura
S
S
Tatsumi
K
K
D042931:Aldehyde Oxidase; D000445:Aldehyde Oxidoreductases / Q000378:metabolism*; D000818:Animals; D001580:Benzopyrenes / Q000378:metabolism*; D006224:Cricetinae; D003600:Cytosol / Q000201:enzymology; D004285:Dogs; D006168:Guinea Pigs; D007700:Kinetics; D008099:Liver / Q000201:enzymology*; D008297:Male; D051379:Mice; D009281:Naphthalenes / Q000378:metabolism*; D010084:Oxidation-Reduction; D011817:Rabbits; D051381:Rats
D001580:Benzopyrenes; D009281:Naphthalenes; C042033:naphthalene 1,2-oxide; C006707:benzo(a)pyrene 4,5-epoxide; D000445:Aldehyde Oxidoreductases; D042931:Aldehyde Oxidase