The kinetics of 1-nitropyrene and 3-nitrofluoranthene metabolism using bovine liver xanthine oxidase

• Published in: Cancer letters Vol. 54; no. 1; pp. 37 - 42
• Main Authors: Bauer, S.L., Howard, P.C.
• Format: Journal Article
• Language: English
• Published: Shannon Elsevier Ireland Ltd 08.10.1990; Elsevier
• Subjects: 1-nitropyrene; 3-nitrofluoranthene; aldehyde oxidase; Animals; bioactivation; Biological and medical sciences; carcinogen; Carcinogenesis, carcinogens and anticarcinogens; Cattle; Chemical agents; Chromatography, High Pressure Liquid; Fluorenes - metabolism; Kinetics; Liver - enzymology; Medical sciences; nitroreduction; Oxidation-Reduction; Oxygen - metabolism; Pyrenes - metabolism; Tumors; Xanthine Oxidase - metabolism; nitroreduction; 1-nitropyrene; aldehyde oxidase; 3-nitrofluoranthene; bioactivation; carcinogen; Nitro compound; Bovine; Enzyme; Liver; Polycyclic aromatic compound; Metabolism; Cofactor; In vitro; Carcinogen; Vertebrata; Reduction; Mammalia; Xanthine oxidase; Artiodactyla; Kinetics; Ungulata
• ISSN: 0304-3835; 1872-7980
• DOI: 10.1016/0304-3835(90)90088-F

The cytosolic molybdoflavoprotein xanthine oxidase has been shown to catalyze the reduction of exocyclic nitro groups to the corresponding nitroso, hydroxylamino and amino derivatives for a wide variety of xenobiotics including the nitrated polycyclic aromatic hydrocarbons 1-nitropyrene and 3-nitrofluoranthene. Using commercially available bovine liver xanthine oxidase, we have studied the kinetics of the metabolism of 1-nitropyrene and 3-nitrofluoranthene. The nitroreduction of these nitro compounds in the presence of xanthine oxidase is dependent on the presence of hypoxanthine or xanthine and the absence of oxygen. This nitroreduction is independent of added flavins (FMN and FAD), unlike the related molybdoflavoprotein aldehyde oxidase. Xanthine oxidase has a K m of 0.7 μM and V max of 0.06 nmol/min per unit enzyme for 1-nitropyrene and a K m of 8.6 μM and V max of 0.7 nmol/min per unit enzyme for 3-nitrofluoranthene. The importance of these kinetic constants in evaluating the cytosolic metabolism of 1-nitropyrene and 3-nitrofluoranthene are discussed.