An in vitro study of hemicholinium-3 on phospholipid metabolism of Krebs II ascites cells.
With [Me-14C]choline as marker and after separation of choline and phosphocholine by ion-exchange column chromatography or thin layer chromatography on alumina, it is shown that 40 microM hemicholinium-3 (HC-3) inhibits the cytosolic choline-kinase of rat liver and Krebs cells. This inhibition is competitive (Km different, Vm similar) in the first case and mixed in the second (Km and Vm different). Despite this general inhibition of the phosphocholine formation, the synthesis of phosphatidylcholine (PC) by post-nuclear supernatants of rat liver and Krebs cells is different when tested with HC-3. It is unaffected in rat liver; however, HC-3 induces a PC deficiency in Krebs cells which is time-course dependent between 15 and 120 min and proportional to the drug concentrations in the interval 5-40 microM. Incorporation of AT-[gamma 32P] or [2-14C]ethanolamine into phospholipids shows that the sequential methylation pathway is not detectable in Krebs cells. These results are discussed in relation to those established concerning HC-3 action on phospholipid metabolism in other tissues.
D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D002287:Carcinoma, Krebs 2 / Q000378:metabolism*; D002794:Choline / Q000096:biosynthesis; D002797:Choline Kinase / Q000037:antagonists & inhibitors*; D019856:Ethanolamine; D004983:Ethanolamines / Q000378:metabolism; D005260:Female; D006426:Hemicholinium 3 / Q000494:pharmacology*; D066298:In Vitro Techniques; D007700:Kinetics; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D051379:Mice; D010713:Phosphatidylcholines / Q000096:biosynthesis; D010743:Phospholipids / Q000378:metabolism*; D010770:Phosphotransferases / Q000037:antagonists & inhibitors*
D004983:Ethanolamines; D010713:Phosphatidylcholines; D010743:Phospholipids; D006426:Hemicholinium 3; D019856:Ethanolamine; D000255:Adenosine Triphosphate; D010770:Phosphotransferases; D002797:Choline Kinase; D002794:Choline