Induction of choline kinase by polycyclic aromatic hydrocarbons in rat liver. II. Its relation to net phosphatidylcholine biosynthesis.
The effect of a single dose (50 mg/kg body weight) of 3-methylcholanthrene on de novo phosphatidylcholine biosynthetic activities in rat liver was studied both in a cell-free system and with slice experiments. 3-Methylcholanthrene caused a significant depression of either [methyl-14C]choline or [2-(3)H]glycerol incorporation into phosphatidylcholine when the precursor was incubated with liver slices. At the same time, there occurred a significant accumulation of radioactivity in either cholinephosphate or diacylglycerol molecule from [14C]choline or [3H]glycerol, respectively, suggesting that 3-methylcholanthrene could cause an inhibitory effect on hepatic phosphatidylcholine synthesis at the cholinephosphotransferase or/and cholinephosphate cytidylyltransferase step. Subsequent studies, where the activities of the three enzymes involved in de novo phosphatidylcholine synthesis were compared between control and 3-methylcholanthrene-pretreated rat liver subcellular fractions, demonstrated that the cholinephosphotransferase step could be the site of inhibition by 3-methylcholanthrene. On the other hand, 3-methylcholanthrene caused a significant induction of choline kinase activity in a time-dependent manner and, at the same time, the cholinephosphate pool size in liver cytosol was enlarged 2-3-fold when compared to the respective control. The overall results suggested strongly that 3-methylcholanthrene causes the counteractive effects on the de novo phosphatidylcholine biosynthesis, induction of choline kinase activity and inhibition of cholinephosphotransferase activity, both of which could participate in a concomitant increase in cholinephosphate pool size in rat liver.
D000818:Animals; D002474:Cell-Free System; D002797:Choline Kinase / Q000096:biosynthesis*; D003566:Cytidine Diphosphate Choline / Q000378:metabolism; D002798:Diacylglycerol Cholinephosphotransferase / Q000378:metabolism; D004075:Diglycerides / Q000378:metabolism; D008055:Lipids / Q000096:biosynthesis; D008099:Liver / Q000201:enzymology*; D008297:Male; D008748:Methylcholanthrene / Q000494:pharmacology*; D010713:Phosphatidylcholines / Q000096:biosynthesis*; D010767:Phosphorylcholine / Q000378:metabolism; D010770:Phosphotransferases / Q000096:biosynthesis*; D051381:Rats; D011919:Rats, Inbred Strains
D004075:Diglycerides; D008055:Lipids; D010713:Phosphatidylcholines; D010767:Phosphorylcholine; D003566:Cytidine Diphosphate Choline; D008748:Methylcholanthrene; D010770:Phosphotransferases; D002797:Choline Kinase; D002798:Diacylglycerol Cholinephosphotransferase