RT Journal Article SR Electronic T1 Co-oxidative Metabolism of 4-Aminobiphenyl by Lipoxygenase from Soybean and Human Term Placenta JF Drug Metabolism and Disposition JO Drug Metab Dispos FD American Society for Pharmacology and Experimental Therapeutics SP 196 OP 105 VO 25 IS 2 A1 Kaushik Datta A1 Paul M. Sherblom A1 Arun P. Kulkarni YR 1997 UL http://dmd.aspetjournals.org/content/25/2/196.abstract AB }4-aminobiphenyl (4-ABP) co-oxidation catalyzed by the human term placental lipoxygenase (HTPLO), purified by affinity chromatography, was studied in the presence of linoleic acid (LA). Soybean lipoxygenase (SLO) which is extensively employed as a model lipoxygenase, was used for comparison. Spectral analyses of reaction media containing 4-ABP, LA, and SLO/HTPLO suggested the disappearance of substrate (ΔA at 270 nm) and a gradual appearance of a new peak at 315 nm, indicating a metabolite formation. Under optimal assay conditions, SLO exhibited a specific activity of 350 nmoles of 4-ABP depleted/min/nmole of enzyme. To observe the maximal rate of co-oxidation by the HTPLO (45 nmoles of 4-ABP depleted/min/mg protein), an incubation of 50 μM 4-ABP, 2 mM LA, and 80 μg/ml protein at pH 7.4 was essential. 4-ABP was also oxidized by SLO in the presence of H2O2, although at a lower rate. The reversed-phase HPLC analysis of organic extracts of the incubations of 4-ABP with SLO and H2O2/LA as well as HTPLO and LA showed the formation of a major peak which was identified by GC-MS as 4,4′-azobis(biphenyl). The addition of GSH, BHT, and BHA to the enzymatic incubations decreased the formation of 4-ABP metabolite, suggesting the generation of a free radical as the initial metabolite during 4-ABP oxidation. Both the SLO and HTPLO mediated reactions were significantly inhibited by nordihydroguaiaretic acid, gossypol, and 5,8,11-eicosatriynoic acid. Collectively, these results suggest that the co-oxidation catalyzed by HTPLO may be the underlying biochemical mechanism responsible for the transplacental toxicity of 4-ABP. The American Society for Pharmacology and Experimental Therapeutics