Co-oxidation of all-trans retinol acetate by human term placental lipoxygenase and soybean lipoxygenase.

The oxidation of all-trans retinol acetate (t-RAc) mediated by soybean lipoxygenase (SLO) and affinity purified human term placental lipoxygenase (HTPLO) was investigated. Under optimum assay conditions, SLO, which is used as a model enzyme, exhibited a specific activity of 850 nmol of t-RAc depleted/min/nmol of enzyme. For HTPLO, incubation of 100 microM t-RAc, 2 mM linoleic acid, and 50 micrograms of enzyme protein in Tris buffer at pH 9.0 was essential to observe the optimum rate of t-RAc cooxidation (370 nmol of t-RAc depleted/min/mg protein). The linoleate dependent cooxidation of t-RAc by both SLO and HTPLO was significantly inhibited by micromolar concentrations of nordihydroguaiaretic acid, butylated hydroxytoluene, butylated hydroxyanisole, gossypol, and 5,8,11-eicosatriynoic acid. These results suggest that t-RAc is metabolized via the lipoxygenase pathway. Significant rate of t-RAc oxidation by HTPLO observed in this study suggests that it may constitute an important part of the puzzle worthy of consideration in the understanding of retinoid teratogenicity in humans.