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Choline levels, the regulation of acetylcholine and phosphatidylcholine synthesis, and Alzheimer’s disease

  • R. J. Wurtman
  • I. H. Ulus
  • J. K. Blusztajn
  • I. Lopez G. Coviella
  • M. Logue
  • C. Mauron
  • J. H. Growdon
Part of the Key Topics in Brain Research book series (KEYTOPICS)

Summary

Circulating choline is converted to membrane phosphatidylcholine (PC) in all cells, and, additionally, to acetylcholine (ACh) within cholinergic neurons. Neither of the enzymes that initiate these processes (choline kinase and choline acetyltransferase) is substrate-saturated; hence supplemental choline can accelerate the formation of both compounds, as well as acetylcholine release from physiologically-active neurons. We have found, using a human neuronal cell line (LA-N-2), that the PC in membranes contributes choline for ACh synthesis. Moreover, using superfused slices of rat brain, we have shown that, when free choline is inadequate to sustain ACh synthesis, the use of the PC “reservoir” for this purpose may deplete membrane PC and other membrane constituents. Hence choline availability may be rate-limiting for membrane formation, as well as for ACh synthesis.

The possibility that abnormalities in choline utilization may be involved in Alzheimer’s disease is demonstrated by the very high levels (twice control) of a PC breakdown product, glycerophosphocholine (GPC), in samples of Alzheimer’s disease brains. This increase could reflect accelerated PC breakdown or an impairment in enzymatic processes that allow free choline to be salvaged from the GPC.

Keywords

Cholinergic Neuron Choline Acetyltransferase Striatal Slice Choline Kinase Choline Level 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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Copyright information

© Springer-Verlag Wien 1990

Authors and Affiliations

  • R. J. Wurtman
    • 1
  • I. H. Ulus
    • 2
  • J. K. Blusztajn
    • 3
  • I. Lopez G. Coviella
    • 1
  • M. Logue
    • 4
  • C. Mauron
    • 1
  • J. H. Growdon
    • 4
  1. 1.Department of Brain and Cognitive SciencesMassachusetts Institute of TechnologyCambridgeUSA
  2. 2.Department of PharmacologyUludag University Medical SchoolBursaTurkey
  3. 3.Department of PathologyBoston University School of MedicineBostonUSA
  4. 4.Department of NeurologyMassachusetts General HospitalBostonUSA

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