Polychlorinated biphenyls increase fatty acid desaturation in the proliferating endoplasmic reticulum of pigeon and rat livers.
1. Polychlorinated biphenyls (PCB) are abundant and persistent pollutants in the ecosystem. Commercial mixtures (e.g. Aroclor 1254) can contain up to 80 different isomers and congeners, many of which accumulate in biological systems by the ingestion of PCB-contaminated lipid components of food chains. 2. Commercial mixtures of PCB induce, in hepatic microsomal membranes in vivo, a variety of different forms of the cytochrome P-450 components of enzyme systems involved in the metabolism of drugs and other xenobiotics, and can also induce the proliferation of this membrane. Since these microsomal enzyme systems share a number of the requirements of microsomal fatty acid desaturases, we have investigated whether the induction by PCB in vivo of cytochrome-P-450-linked enzymes in the proliferating hepatic microsomal membrane of the pigeon and the rat is accompanied by increased proportions of polyunsaturated fatty acids in this membrane. 3. The most striking changes observed 120 h after treating pigeons and rats with 1.5 mmol Aroclor 1254/kg body mass were 2.2-fold and 1.6-fold increases, respectively, in the proportion of arachidonic acid in the hepatic microsomal membrane. When the effects of this treatment on the proliferation of this membrane and increase in liver mass are taken into account, the amount of arachidonic acid in the total microsomal membrane of pigeon and rat livers increased 6.7-fold and 1.9-fold, respectively. 4. These changes were accompanied by very significant increases in pigeons and rats of the concentration of hepatic microsomal cytochrome P-450, and in the activity in microsomal protein of a wide range of cytochrome P-450-dependent enzyme involved in the metabolism of drugs and other xenobiotics. 5. This effect of PCB, of increasing in vivo the degree of unsaturation of fatty acids of hepatic microsomal membrane, appears to be a novel finding, and does not seem to have been investigated for other drugs and xenobiotics. Preliminary results have shown that the effect is accompanied by substantial increases in the total activity of delta 6 and delta 5 microsomal fatty acid desaturases converting 18:2 (9, 12) (linoleic acid) to 20:4 (5, 8, 11, 14) (arachidonic acid) [Borlakoglu, J.T., Dils, R.R., Edwards-Webb, J.D. & Walker, C.H. (1988) Biochem. Soc. Trans. 16, 1072]. 6. It is postulated that there is a significant link between increased fatty acid desaturation and the induction of cytochrome-P-450-linked enzymes, and this is discussed in terms of the mechanisms involved in the metabolism of foreign compounds.
Borlakoglu
J T
JT
Department of Biochemistry and Physiology, University of Reading, England.
Edwards-Webb
J D
JD
Dils
R R
RR
D000818:Animals; D010856:Columbidae; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D004721:Endoplasmic Reticulum / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D004785:Environmental Pollutants / Q000494:pharmacology; D004790:Enzyme Induction / Q000187:drug effects; D044943:Fatty Acid Desaturases / Q000378:metabolism*; D005227:Fatty Acids / Q000378:metabolism*; D008658:Inactivation, Metabolic; D008563:Membrane Lipids / Q000378:metabolism; D008862:Microsomes, Liver / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D011078:Polychlorinated Biphenyls / Q000494:pharmacology*; D051381:Rats
D004785:Environmental Pollutants; D005227:Fatty Acids; D008563:Membrane Lipids; D003577:Cytochrome P-450 Enzyme System; D011078:Polychlorinated Biphenyls; D044943:Fatty Acid Desaturases