Abstract
The objective of the present study was to estimate the maximal velocity ( V max) and Michaelis affinity constant ( K m) for the oxidation of pyrene to 1-hydroxypyrene using rat liver post-mitochondrial fractions. The approach involved the determination of the concentrations of 1-hydroxypyrene formed during 5 min incubations of pyrene (initial concentrations: 0.0025–0.5 μM), and correcting for the rate of 1-hydroxypyrene disappearance (2.16×10 −5 per (mg protein/l)/min) during the incubation period. The V max and K m for pyrene metabolism in the rat corresponded to 0.0577±0.0108 μmol/min per g liver and 27.73±13.54 μM, respectively. The intrinsic clearance ( CL int) of pyrene in the rat estimated in the present study (0.041–0.111 l/min per kg) was within the range of the previously reported CL int in humans (0.037–0.125 l/min per kg). The results of this study suggest that CL int of pyrene in humans can be predicted from such data obtained in the rat.
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