Synthesis of acetylcholine from choline derived from phosphatidylcholine in a human neuronal cell line
Cholinergic neurons are unique among cells since they alone utilize choline not only as a component of major membrane phospholipids, such as phosphatidylcholine (Ptd-Cho), but also as a precursor of their neurotransmitter acetylcholine (AcCho). It has been hypothesized that choline-phospholipids might serve as a storage pool of choline for AcCho synthesis. The selective vulnerability of cholinergic neurons in certain neurodegenerative diseases (e.g., Alzheimer disease, motor neuron disorders) might result from the abnormally accelerated liberation of choline (to be used a precursor of AcCho) from membrane phospholipids, resulting in altered membrane composition and function and compromised neuronal viability. However, the proposed metabolic link between membrane turnover and AcCho synthesis has been difficult to demonstrate because of the heterogeneity of the preparations used. Here the authors used a population of purely cholinergic cells (human neuroblastomas, LA-N-2), incubated in the presence of (methyl-/sup 3/H)methionine to selectively label PtdCho synthesized by methylation of phosphatidylethanolamine, the only pathway of de novo choline synthesis. Three peaks of radioactive material that cochromatographed with authentic AcCho, choline, and phosphocholine were observed when the water-soluble metabolites of the (/sup 3/H)PtdCho were purified by high-performance liquid chromatography. The results demonstrate that AcCho can be synthesized from choline derived from the degradation of endogenous PtdCho formed de novo by methylation of phosphatidylethanolamine.
- Research Organization:
- Massachusetts Institute of Technology, Cambridge (USA)
- OSTI ID:
- 5298135
- Journal Information:
- Proc. Natl. Acad. Sci. U.S.A.; (United States), Vol. 84:15
- Country of Publication:
- United States
- Language:
- English
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Related Subjects
ACETYLCHOLINE
BIOSYNTHESIS
NERVOUS SYSTEM DISEASES
PATHOGENESIS
TRITIUM COMPOUNDS
BIODEGRADATION
CHOLINE
METHYLATION
NERVE CELLS
PHOSPHOLIPIDS
TUMOR CELLS
ALCOHOLS
AMINES
AMMONIUM COMPOUNDS
ANIMAL CELLS
AUTONOMIC NERVOUS SYSTEM AGENTS
CHEMICAL REACTIONS
DECOMPOSITION
DISEASES
DRUGS
ESTERS
HYDROXY COMPOUNDS
LABELLED COMPOUNDS
LIPIDS
LIPOTROPIC FACTORS
NEUROREGULATORS
ORGANIC COMPOUNDS
ORGANIC PHOSPHORUS COMPOUNDS
PARASYMPATHOMIMETICS
QUATERNARY COMPOUNDS
SOMATIC CELLS
SYNTHESIS
550201* - Biochemistry- Tracer Techniques