Mapping choline metabolites in normal and transformed cells.

Area of Science:

• Biochemistry
• Cell Biology
• Cancer Metabolism

Background:

• Choline is an essential nutrient vital for proliferating cells.
• Altered choline metabolism is linked to cancer development.
• The metabolic pathways of choline in proliferating cells remain incompletely understood.

Purpose of the Study:

• To comprehensively map choline's metabolic products in normal and cancerous proliferating cells.
• To identify novel choline metabolites and understand their roles in cancer.

Main Methods:

• Utilized 13C-choline tracing in normal, in vitro-transformed, and cancer cell lines.
• Employed liquid chromatography-high resolution mass spectrometry (LC-HRMS) for metabolic product analysis.
• Quantified selected metabolites using internal standards.

Main Results:

• Identified 121 13C-labeled choline metabolites, including novel monomethyl- and dimethyl-ethanolamines.
• Observed specific betaine synthesis from choline in tumor-derived cells.
• Found correlation between choline dehydrogenase (CHDH) expression and betaine synthesis; CHDH RNAi affected cell cycle progression.

Conclusions:

• This research uncovers new choline metabolites in both normal and cancer cell lines.
• Demonstrates distinct alterations in choline metabolism within cancer cells.
• Suggests a potential role for betaine and CHDH in cancer cell cycle progression, though betaine's precise function remains undetermined.