Feedback regulation of CTP:phosphocholine cytidylyltransferase translocation between cytosol and endoplasmic reticulum by phosphatidylcholine.
The mechanism for the increased association of CTP:phosphocholine cytidylyltransferase (CT) with membranes of hepatocytes derived from choline-deficient, compared with choline-supplemented rats, has been investigated. The cells were maintained in culture for 4 h in a choline- and methionine-deficient medium. (Methionine is required for synthesis of phosphatidylcholine (PC) via methylation of phosphatidylethanolamine.) Afterward, the cells were incubated +/- choline for various times up to 4 h. In the presence, but not in the absence, of choline there was a translocation of CT activity from membranes to cytosol. During this time period there was no change in the amounts of unesterified fatty acids or diacylglycerol recovered from the hepatocytes. In addition, there was no evidence for a difference in the incorporation of 32P into CT or other cytosolic proteins isolated from hepatocytes +/- choline. In contrast, there was a highly significant correlation between the concentration of PC in the membranes and the increased activity of CT in the cytosol (R = 0.98) and the decreased activity in the membranes (R = 0.93). The concentration of PC could alternatively be altered by incubation of the choline-deficient hepatocytes with methionine or lyso-PC. With either of these supplementations highly significant correlation coefficients were observed between the concentration of PC in membranes and decreased activity of CT in membranes or increased activity in cytosol. The concentration of PC was reduced in the endoplasmic reticulum, but not the Golgi membranes, isolated from choline-deficient compared with choline-supplemented livers. The data suggest that the amount of PC in the endoplasmic reticulum feedback regulates the amount of CT associated with this membrane.
Jamil
H
H
Lipid and Lipoprotein Research Group, University of Alberta, Edmonton, Canada.
Yao
Z M
ZM
Vance
D E
DE
D001692:Biological Transport / Q000187:drug effects; D002794:Choline / Q000494:pharmacology; D002796:Choline Deficiency / Q000201:enzymology*; D019916:Choline-Phosphate Cytidylyltransferase; D003600:Cytosol / Q000201:enzymology*; D004075:Diglycerides / Q000378:metabolism; D004721:Endoplasmic Reticulum / Q000201:enzymology* / Q000378:metabolism; D005227:Fatty Acids / Q000378:metabolism; D005246:Feedback; D006056:Golgi Apparatus / Q000378:metabolism; D006706:Homeostasis; D008099:Liver / Q000201:enzymology* / Q000648:ultrastructure; D008244:Lysophosphatidylcholines / Q000494:pharmacology; D008715:Methionine / Q000494:pharmacology; D009713:Nucleotidyltransferases / Q000378:metabolism*; D010713:Phosphatidylcholines / Q000378:metabolism / Q000494:pharmacology*; D010766:Phosphorylation
D004075:Diglycerides; D005227:Fatty Acids; D008244:Lysophosphatidylcholines; D010713:Phosphatidylcholines; D008715:Methionine; D009713:Nucleotidyltransferases; D019916:Choline-Phosphate Cytidylyltransferase; D002794:Choline