Early stimulation of phosphatidylcholine biosynthesis during Wallerian degeneration of rat sciatic nerve.
Phospholipid metabolism was studied in rat sciatic nerve during Wallerian degeneration induced by crush injury. Portions of crushed sciatic nerve, incubated with labeled substrates, showed significantly higher phosphatidylcholine synthesis than normal nerve, prior to any measurable alterations of phospholipid composition. Maximum synthesis occurred 3 days after crush injury, at which time the metabolism of other phospholipids was unchanged. After a rapid decrease in biosynthetic activity, a second phase of enhanced phosphatidylcholine synthesis occurred, beginning 6 days after crush injury. Increased incorporation of [33P]phosphate, [2-3H]glycerol, and [Me-14C]choline indicated stimulation of de novo synthesis of phosphatidylcholine 3 days after injury. Neither base exchange reactions nor sequential methylation of ethanolamine phospholipids contributed significantly to phosphatidylcholine synthesis. Assay of certain key enzymes under optimal conditions in subcellular fractions of sciatic nerve revealed higher activities of cholinephosphate cytidyltransferase, choline phosphotransferase, and acyl-CoA:lysophosphatidylcholine acyltransferase in injured nerve, while choline kinase activity remained unchanged. This indicates that stimulation of phosphatidylcholine synthesis occurs via the cytidine nucleotide pathway, as well as by increased acylation of lysophosphatidylcholine. Although the cause of stimulated phosphatidylcholine synthesis remains unexplained, it is possible that trace amounts of lysophospholipids or other metabolites produced by injury-enhanced phospholipase activity may be responsible.
D000818:Animals; D002794:Choline / Q000031:analogs & derivatives / Q000378:metabolism; D002797:Choline Kinase / Q000378:metabolism; D019916:Choline-Phosphate Cytidylyltransferase; D002798:Diacylglycerol Cholinephosphotransferase / Q000378:metabolism; D005990:Glycerol / Q000378:metabolism; D008297:Male; D009410:Nerve Degeneration; D009713:Nucleotidyltransferases / Q000378:metabolism; D010710:Phosphates / Q000378:metabolism; D010713:Phosphatidylcholines / Q000096:biosynthesis*; D051381:Rats; D011919:Rats, Inbred Strains; D012584:Sciatic Nerve / Q000502:physiology*; D014855:Wallerian Degeneration
D010710:Phosphates; D010713:Phosphatidylcholines; C017506:methylcholine; D002797:Choline Kinase; D009713:Nucleotidyltransferases; D019916:Choline-Phosphate Cytidylyltransferase; D002798:Diacylglycerol Cholinephosphotransferase; D002794:Choline; D005990:Glycerol