Glutathione conjugation of the carcinogenic and mutagenic electrophile (+/-)-7 beta, 8 alpha-dihydroxy-9 alpha, 10 alpha-oxy-7,8,9,10-tetra hydrobenzo[a]pyrene catalyzed by purified rat liver glutathione transferases.
The kinetics of the enzyme-catalyzed conjugation of (+/-)-7 beta, 8 alpha-dihydroxy-9 alpha, 10 alpha-oxy-7,8,9,10-tetrahydrobenzo[a]-pyrene [(+/-)-anti-BPDE] with glutathione (GSH) by the following purified soluble rat liver GSH transferases: 1-1, 1-2, 2-2, 3-3, 3-4 and 4-4 have been studied. When BPDE concentration was varied while GSH concentration remained constant (1 mM), linear Lineweaver-Burk plots were obtained: maximum rates of conjugation mediated by GSH transferases 1-1, 1-2, 2-2, 3-3, 3-4 and 4-4 were 105, 72, 83, 35, 179 and 357 nmol/min/mg protein, respectively. When GSH concentration was varied while BPDE concentration remained constant (40 microM), biphasic Lineweaver-Burk plots were obtained in each case with a break point of 0.2 mM GSH below which the affinity of these enzymes for GSH was apparently greater. These results are discussed with respect to the detoxication of benzo[a]pyrene (BP) in vivo.
D015123:7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide; D000818:Animals; D001580:Benzopyrenes / Q000378:metabolism*; D002273:Carcinogens / Q000378:metabolism*; D005978:Glutathione / Q000378:metabolism*; D005982:Glutathione Transferase / Q000494:pharmacology*; D008658:Inactivation, Metabolic; D007700:Kinetics; D008099:Liver / Q000201:enzymology / Q000378:metabolism*; D008297:Male; D009153:Mutagens / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains
D001580:Benzopyrenes; D002273:Carcinogens; D009153:Mutagens; D015123:7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide; D005982:Glutathione Transferase; D005978:Glutathione