RATE OF PYRENE METABOLISM IN RAT-LIVER POST-MITOCHONDRIAL FRACTIONS

The objective of the present study was to estimate the maximal velocit y (V-max) and Michaelis affinity constant (K-m) for the oxidation of p yrene to 1-hydroxypyrene using rat liver post-mitochondrial fractions. The approach involved the determination of the concentrations of 1-hy droxypyrene formed during 5 min incubations of pyrene (initial concent rations: 0.0025-0.5 mu M), and correcting for the rate of 1-hydroxypyr ene disappearance (2.16 x 10(-5) per (mg protein/l)/min) during the in cubation period. The V-max and K-m for pyrene metabolism in the rat co rresponded to 0.0577 +/- 0.0108 mu mol/min per g liver and 27.73 +/- 1 3.54 mu M, respectively. The intrinsic clearance (CLint) 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 CLint in humans (0.037-0.1 25 l/min per kg). The results of this study suggest that CLint of pyre ne in humans can be predicted from such data obtained in the rat. (C) 1997 Elsevier Science Ireland Ltd.