Evidence for the induction of fatty acid desaturation in proliferating hepatic endoplasmic reticulum in response to treatment with polychlorinated biphenyls. Are fatty acid desaturases cytochrome P-450-dependent monooxygenases?
1. Polychlorinated biphenyls (PCBs) are abundant and persistent pollutants in the ecosystem which accumulate in biological systems. 2. We have shown previously (Borlakoglu et al., 1990; Eur. J. Biochem. 118, 327-332) that 120 hr after treating pigeons and rats with 1.5 mmol Aroclor 1254/kg body weight, hepatic microsomal membranes showed significant increases in the proportion of arachidonate (20:4,5, 8,11,14), in the concentration of cytochrome P-450 and in the activities of a wide range of cytochrome P-450-dependent enzymes involved in the metabolism of drugs and other xenobiotics. 3. After treating pigeons and rats in vivo with Aroclor 1254, linoleate desaturases activity increased significantly 3.35-, 4.35-, 5.83- and 8.61-fold 24, 48, 68 and 120 hr for pigeons and 2- and 7-fold for rats respectively 48 and 120 hr post treatment. The total activity of linoleate desaturases in the whole liver of pigeons and rats increased 40- and 10-fold respectively. 4. There were excellent correlations between the concentrations of cytochrome b5 and cytochrome P-450 and the activity of pigeon linoleate desaturases. Extrapolation of the concentration of cytochrome P-450 to zero is coincident with zero linoleate desaturase activity. 5. Evidence is presented to suggest the novel concept that linoleate desaturation is dependent upon the catalytic cycle of these monooxygenases.
Borlakoglu
J T
JT
Department of Biochemistry and Physiology, University of Reading, Whiteknights, UK.
Edwards-Webb
J D
JD
Dils
R R
RR
D000818:Animals; D001140:Aroclors / Q000494:pharmacology*; D020111:Chlorodiphenyl (54% Chlorine); D010856:Columbidae; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D004721:Endoplasmic Reticulum / Q000378:metabolism*; D044943:Fatty Acid Desaturases / Q000187:drug effects / Q000378:metabolism*; D005227:Fatty Acids / Q000378:metabolism; D050602:Linoleoyl-CoA Desaturase; D008099:Liver / Q000378:metabolism*; D010105:Oxygenases / Q000378:metabolism*; D051381:Rats
D001140:Aroclors; D005227:Fatty Acids; D020111:Chlorodiphenyl (54% Chlorine); D003577:Cytochrome P-450 Enzyme System; D010105:Oxygenases; D044943:Fatty Acid Desaturases; D050602:Linoleoyl-CoA Desaturase