Rate of pyrene metabolism in rat liver post-mitochondrial fractions.
The objective of the present study was to estimate the maximal velocity (Vmax) and Michaelis affinity constant (Km) 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 microM), and correcting for the rate of 1-hydroxypyrene disappearance (2.16 x 10(-5) per (mg protein/l)/min) during the incubation period. The Vmax and Km for pyrene metabolism in the rat corresponded to 0.0577 +/- 0.0108 micromol/min per g liver and 27.73 +/- 13.54 microM, 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.
Haddad
S
S
Groupe de recherche en Toxicologie Humaine (TOXHUM), Faculté de médecine, Université de Montréal, Que., Canada.
Tardif
R
R
Withey
J
J
Krishnan
K
K
D000818:Animals; D004785:Environmental Pollutants / Q000378:metabolism; D066298:In Vitro Techniques; D008099:Liver / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D008297:Male; D011721:Pyrenes / Q000378:metabolism* / Q000493:pharmacokinetics; D051381:Rats; D017207:Rats, Sprague-Dawley
D004785:Environmental Pollutants; D011721:Pyrenes; C030984:pyrene