A highly toxic coplanar polychlorinated biphenyl compound suppresses Delta5 and Delta6 desaturase activities which play key roles in arachidonic acid synthesis in rat liver.
The effect of 3,3',4,4',5-pentachlorobiphenyl (PenCB) on the synthesis of unsaturated fatty acids was studied in male Wistar rats. The arachidonic acid (20:4) content in the total lipids of liver homogenates was significantly reduced on day 5 of PenCB administration, while those of linoleic acid (18:2) and bishomo-gamma-linolenic acid (20:3) were increased. These changes in the total lipids of liver homogenates were observed following doses of PenCB ranging from 0.5 to 25 mg/kg of body weight. The same changes in these fatty acids were seen with four subtypes of microsomal glycerophospholipids in the liver. The marked reduction in the molar ratio of 20:4 to 18:2 in the lipids suggests alteration of the activity of the enzymes responsible for the synthesis of unsaturated fatty acids. The activity of Delta5 and Delta6 desaturases (arachidonic acid synthetase) in the liver microsomes was 17 and 13% of that of pair-fed control animals, whereas the activity of 1-acylglycerophosphorylcholine or 1-acylglycerophosphate acyltransferase, which transfers 20:4 or 18:2 to phospholipids, was not affected by the treatment. Thus, the reduction in the level of 20:4 that was observed can be explained by a reduction in desaturase activity. These results are evidence that the coplanar PenCB has a significant effect on the reduced synthesis of physiologically essential long-chain unsaturated fatty acids.
Matsusue
K
K
Graduate School of Pharmaceutical Sciences, Kyushu University 62, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan.
Ishii
Y
Y
Ariyoshi
N
N
Oguri
K
K
D000818:Animals; D016718:Arachidonic Acid / Q000096:biosynthesis*; D000090943:Delta-5 Fatty Acid Desaturase; D044943:Fatty Acid Desaturases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D020404:Glycerophospholipids / Q000378:metabolism; D019787:Linoleic Acid / Q000378:metabolism; D050602:Linoleoyl-CoA Desaturase; D008297:Male; D008862:Microsomes, Liver / Q000187:drug effects* / Q000201:enzymology; D011078:Polychlorinated Biphenyls / Q000494:pharmacology* / Q000633:toxicity; D051381:Rats; D017208:Rats, Wistar
D000090943:Delta-5 Fatty Acid Desaturase; D020404:Glycerophospholipids; D016718:Arachidonic Acid; D019787:Linoleic Acid; D011078:Polychlorinated Biphenyls; D044943:Fatty Acid Desaturases; D050602:Linoleoyl-CoA Desaturase; C023035:3,4,5,3',4'-pentachlorobiphenyl