Inhibition of phosphatidylcholine biosynthesis

Figure 3. Inhibition of phosphatidylcholine biosynthesis by apoptosis-inducing compounds. The target enzyme for the inhibition of PC biosynthesis is shown for several compounds that have further in common that they all induce apoptosis. Abbreviations are as follows CK, choline kinase CPT, cholinephosphotransferase CT, CTP phosphocholine cytidylyltransferase PC, phosphatidylcholine.

Anthony, M.L., Zhao, M., and Brindle, K.M., 1999, Inhibition of phosphatidylcholine biosynthesis following induction of apoptosis in HL-60 cells. J. Biol. Chem. 274 19686-19692... 

Houwehng, M., 1999b, Inhibition of phosphatidylcholine and phosphatidylethanolamine biosynthesis in rat-2 fibroblasts by cell-permeable ceramides. Eur. J. Biochem. 264 152-160... 

The energy state of the cell dictates the relative rates of phosphatidylcholine, phosphatidylethanolamine, and triacylglycerol biosynthesis. When energy is in short supply, the level of cAMP rises leading to inhibition of fatty acid biosynthesis (see chapter 18). This in turn decreases the supply of diacylglycerol, which limits the synthesis of phosphatidylcholine, phosphatidylethanolamine, and triacylglycerol. When sufficient diacylglycerol is pres-... 

There are few commercial fungicides that have glycerophospholipid biosynthesis inhibition as their mode of action. The validated targets are phosphatidylcholine synthesis and phosphatidylinositol synthesis. 

If depressants inhibit the utilization of energy-rich phosphates, phospholipid biosynthesis might be expected to be affected. With a dose of 60 mg/kg body weight of thiopentone [5-ethyl-5-(l-methylbutyl)-2-thio-barbitone], Dawson and Richter (1950b) convincingly demonstrated a reduction in the rate of transfer of labeled phosphate from the water-soluble pool to the phospholipids of mouse brain. This was not due to the hypothermia induced by the anesthetic. Ansell and Dohmen (1957) confirmed this for a number of phospholipids, including phosphatidylcholine and -ethanolamine. It was subsequenUy shown that the phosphorylation of the bases choline and ethanolamine was unaffected (Ansell, 1960). This was presumably a consequence of the unchanged level of ATP. 

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