Document Detail


Metabolism of the 'organic osmolyte' glycerophosphorylcholine in isolated rat inner medullary collecting duct cells. I. Pathways for synthesis and degradation.
MedLine Citation:
PMID:  8504126     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
In isolated inner medullary collecting duct (IMCD) cells the adaptation to changes in extracellular osmolarity involves alterations in intracellular content of organic osmolytes such as glycerophosphorylcholine (GPC), sorbitol and others. To elucidate the basis of such alterations, the metabolism of GPC in IMCD cells was investigated with the labeled GPC precursor [methyl-3H]choline. The lipids phosphatidylcholine (PC), lyso PC (LPC) and sphingomyelin (SM), as well as the non lipids phosphorylcholine (Pcholine), GPC and an unknown water-soluble compound could be identified as intermediates of choline metabolism. In pulse-chase experiments the radioactivity of PC expressed as specific activity was at a higher level than the other metabolites (> 10-fold after 1h). Extended chase incubations caused the specific activity of PC and LPC to decrease significantly. GPC was the only metabolite with a significant increase in specific activity under these conditions, suggesting that PC (via LPC) could be the precursor of GPC. In short-term pulse experiments the specific activity of PC and LPC was always significantly higher compared to the specific activity of GPC. Pulse chase incubations using phosphatidyl[methyl-3H]choline showed a significant decrease in specific activity of PC after 15 h accompanied by a significant increase in specific activity of LPC as well as GPC. Inhibition of the PC hydrolyzing enzyme phospholipase A2 revealed a significant increase in the specific activity of PC. For GPC, a significant decrease in the radioactive labeling could be detected. The total amount of PC decreased by 10% under these conditions whereas the amount of GPC decreased by 22% which was significantly higher because of GPC breakdown. GPC degradation was catalyzed by GPC: choline diesterase generating choline (and phosphoglycerol). Significant activity of GPC:phosphocholine diesterase could not be detected. Betaine synthesis from choline was also not present. The slowest, and probably rate-limiting reaction of GPC synthesis from choline may be the reaction of phosphocholine cytidylyltransferase generating CDP choline, since no radioactive CDP choline could be detected under any conditions. Thus, isolated IMCD cells possess the ability for the synthesis of GPC from choline via PC and LPC, as well as for the GPC degradation to choline (and phosphoglycerol). Significant experimental evidence for the occurrence of de-novo synthesis of GPC from choline or a precursor function of GPC for PC could not be detected. However, although the former possibility seems unlikely, a final proof is still lacking.
Authors:
H G Bauernschmitt; R K Kinne
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Publication Detail:
Type:  In Vitro; Journal Article    
Journal Detail:
Title:  Biochimica et biophysica acta     Volume:  1148     ISSN:  0006-3002     ISO Abbreviation:  Biochim. Biophys. Acta     Publication Date:  1993 Jun 
Date Detail:
Created Date:  1993-07-02     Completed Date:  1993-07-02     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  0217513     Medline TA:  Biochim Biophys Acta     Country:  NETHERLANDS    
Other Details:
Languages:  eng     Pagination:  331-41     Citation Subset:  IM    
Affiliation:
Max-Planck-Institut für molekulare Physiologie, Dortmund Germany.
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MeSH Terms
Descriptor/Qualifier:
Animals
Choline / metabolism
Glycerylphosphorylcholine / biosynthesis,  metabolism*
Kidney Medulla / metabolism*
Kidney Tubules, Collecting / metabolism*
Male
Phosphatidylcholines / metabolism
Rats
Rats, Wistar
Chemical
Reg. No./Substance:
0/Phosphatidylcholines; 563-24-6/Glycerylphosphorylcholine; 62-49-7/Choline

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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