Document Detail

Enhancement of free fatty acid incorporation into phospholipids by choline plus cytidine.
MedLine Citation:
PMID:  10082883     Owner:  NLM     Status:  MEDLINE    
Cytidine and choline, present in cytidine 5'-diphosphate choline (CDP-choline), are major precursors of the phosphatidylcholine found in cell membranes and important regulatory elements in phosphatide biosynthesis. Administration of CDP-choline to rats increases blood and brain cytidine and choline levels; this enhances the production of endogenous CDP-choline which then combines with fatty acids (as diacylglycerol), to yield phosphatidylcholine. We examined the effect of providing cytidine and choline on incorporation of free fatty acids into phosphatidylcholine and other major phospholipids in PC12 cells. Addition of equimolar cytidine and choline (100-500 microM) to [3H]-arachidonic acid (50 microM, 0.2 microCi, bound to bovine serum albumin) dose-dependently increased the accumulations of [3H]-phosphatidylcholine (PtdCho), [3H]-phosphatidylinositol (PtdIno) and [3H]-phosphatidylethanolamine (PtdEtn) (by up to 27+/-3%, 16+/-3% and 11+/-3%, respectively, means+/-S.E.M.). This effect was seen with 8-18 h of incubation. The incorporation of [3H]-oleic acid into [3H]-PtdCho was even more enhanced (by up to 42+/-3%) as were the incorporations of [14C]-choline and [3H]-glycerol. The effects of choline and cytidine were enhanced by 12-O-tetradecanoylphorbol-13-acetate (TPA, 1 microM), which activates CTP:phosphocholine cytidylyltransferase (CT) and facilitates choline uptake. Replacing choline by ethanolamine also enhanced the incorporation of [3H]-arachidonic acid into [3H]-PtdEtn, [3H]-PtdIno and [3H]-PtdCho. Arachidonic acid (10-200 microM) alone failed to affect the incorporation of [14C]-choline into phosphatidylcholine. We suggest that the increases in phospholipid synthesis caused by concurrent cytidine and choline supplementation enhance the incorporation of arachidonic acid and certain other fatty acids into the major glycerophospholipids. Removing these fatty acids as source of potentially toxic oxidation products could contribute to the beneficial effects of CDP-choline in treating stroke or other brain damage.
S Knapp; R J Wurtman
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Brain research     Volume:  822     ISSN:  0006-8993     ISO Abbreviation:  Brain Res.     Publication Date:  1999 Mar 
Date Detail:
Created Date:  1999-04-21     Completed Date:  1999-04-21     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  0045503     Medline TA:  Brain Res     Country:  NETHERLANDS    
Other Details:
Languages:  eng     Pagination:  52-9     Citation Subset:  IM    
Copyright Information:
Copyright 1999 Elsevier Science B.V.
Massachusetts Institute of Technology, Department of Brain and Cognitive Sciences, E25-604, Cambridge, MA 02139, USA.
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MeSH Terms
Arachidonic Acid / metabolism,  pharmacology
Carbon Radioisotopes / diagnostic use
Carcinogens / pharmacology
Choline / pharmacology*
Choline-Phosphate Cytidylyltransferase / metabolism
Cytidine / pharmacology*
Cytidine Triphosphate / analogs & derivatives,  pharmacology
Enzyme Inhibitors / pharmacology
Ethanolamine / pharmacology
Fatty Acids, Nonesterified / metabolism*
Glycerol / metabolism,  pharmacology
Neurons / drug effects,  enzymology*
PC12 Cells
Phospholipids / metabolism*
Tetradecanoylphorbol Acetate / pharmacology
Tritium / diagnostic use
Reg. No./Substance:
0/Carbon Radioisotopes; 0/Carcinogens; 0/Enzyme Inhibitors; 0/Fatty Acids, Nonesterified; 0/Phospholipids; 10028-17-8/Tritium; 118045-71-9/cyclopentenylcytosine 6-triphosphate; 141-43-5/Ethanolamine; 16561-29-8/Tetradecanoylphorbol Acetate; 506-32-1/Arachidonic Acid; 56-81-5/Glycerol; 62-49-7/Choline; 65-46-3/Cytidine; 65-47-4/Cytidine Triphosphate; EC Cytidylyltransferase

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