Activity of the phosphatidylcholine biosynthetic pathway modulates the distribution of fatty acids into glycerolipids in proliferating cells

• Published in: Biochimica et biophysica acta 2000-01, Vol.1483 (3), p.301-315
• Main Authors: Jackowski, Suzanne, Wang, Jina, Baburina, Irina
• Format: Article
• Language: English
• Subjects: Acetates - metabolism; Acetyl-CoA Carboxylase - antagonists & inhibitors; Acetyl-CoA Carboxylase - genetics; Acetyl-CoA Carboxylase - metabolism; Animals; Cell Cycle; Cell Line; Cell proliferation; Cerulenin - pharmacology; CHO Cells; Choline-Phosphate Cytidylyltransferase - antagonists & inhibitors; Choline-Phosphate Cytidylyltransferase - metabolism; Colony stimulating factor 1; Cricetinae; CTP:phosphocholine cytidylyltransferase; Diacylglycerol; Diglycerides - metabolism; Fatty Acid Synthases - genetics; Fatty Acid Synthases - metabolism; Fatty acid synthesis; Fatty Acids - biosynthesis; Glycerolipid; Growth factor; Macrophage Colony-Stimulating Factor - pharmacology; Mice; Mice, Inbred BALB C; Mitogens; Phosphatidylcholine; Phosphatidylcholines - biosynthesis; Temperature; Triacylglycerol regulation; Triglycerides - biosynthesis; Tritium
• ISSN: 1388-1981; 0006-3002; 1879-2618
• DOI: 10.1016/S1388-1981(99)00203-6

PtdCho accumulation is a periodic, S phase-specific event that is modulated in part by cell cycle-dependent fluctuations in CTP:phosphocholine cytidylyltransferase (CCT) activity. A supply of fatty acids is essential to generate the diacylglycerol (DG) precursors for phosphatidylcholine (PtdCho) biosynthesis but it is not known whether the DG supply is also coupled to the cell cycle. Although the rate of fatty acid synthesis in a macrophage cell line was dramatically stimulated in response to the growth factor, CSF-1, it was not regulated by the cell cycle. Increased fatty acid synthesis correlated with elevated acetyl-CoA carboxylase (ACC) and fatty acid synthase (FAS) steady-state mRNA levels. Cellular fatty acid synthesis was essential for membrane PL synthesis. Cerulenin inhibition of endogenous fatty acid synthesis also inhibited PtdCho synthesis, which was not relieved by exogenous fatty acids. Inhibition of CCT activity by the addition of lysophosphatidylcholine (lysoPtdCho) or temperature-shift of a conditionally defective CCT diverted newly synthesized DG to the TG pool where it accumulated. Enforced expression of CCT stimulated PtdCho biosynthesis and reduced TG synthesis. Thus, the cellular DG supply did not regulate PtdCho biosynthesis and CCT activity governs the partitioning of DG into either the PL or TG pools, thereby controlling both PtdCho and TG biosynthesis.