Oleate stimulation of diacylglycerol formation from phosphatidylcholine through effects on phospholipase D and phosphatidate phosphohydrolase

Abstract

Hydrolysis of exogenous phosphatidylcholine (PtdCho) to 1,2-diacyIglycerol by rat liver plasma membranes was stimulated by oleate concentrations as low as 0.1 mM. In the presence of 75 mM ethanol, the falty acid also enhanced phosphatidylethanol (PtdEtOH) formation from PtdCho. These effects were also observed with linoleate and arachidonate, but not with saturated fatty acids or detergents, and were minimal in microsomes or mitochondria. Kelease of [3H]choline from exogenous Pt~l[~H]Cho was stimulated by oleate, whereas ph~sphoryl[~H]choline formation was inhibited. Oleate and other unsaturated, but not saturated, fatty acids also stimulated the conversion of exogenous ['4C]phosphatidic acid to ['4C]diacylglycerol. These data are consistent with stimulatory effects of these fatty acids on both phospholipase D and phosphatidate phosphohydrolase in liver plasma membranes. The stimulatory effect of guanosine 5'-0-[3-thio]triphosphate) (20 pM) on PtdEtOH and diacylglycerol formation from PtdCho was enhanced by low concentrations of oleate. Phospholipase A2 also stimulated PtdEtOH and diacylglycerol formation from exogenous PtdCho. It is proposed that unsaturated fatty acids may play a physiological role in the regulation of diacylglycerol production through activation of phospholipasc D and phosphatidate phosphohydrolase.

31P NMR measurements of the effects of unsaturated fatty acids on cellular phospholipid metabolism

“…Nevertheless, the important point is that the phospholipases present in HL60 and myeloma cells can be stimulated by unsaturated fatty acids. Stearic acid had no effect on either enzyme, as has also been observed previously (10). This is consistent with the absence of any effect of stearic acid on the PE/NTP ratio in the cell lines that were studied in most detail, the human leukemic cell line, HL60 (Table l), and the mouse myeloma cell line ( Table 2).…”

Modulation of enzymatic activities by n-3 polyunsaturated fatty acids to support cardiovascular health

“…It is not known if a similar mechanism of action for n-3 PUFA activation of PLD exists in cardiomyocytes. However, based on DHA distribution in lipid domains, it is expected that n-3 PUFAs may have a stimulatory effect on PLD activation in the heart and may play a physiological role in the regulation of DAG production by activating PLD and PA phosphohydrolase activity, as previously suggested [93]. PLA 2 is another physiologically important enzyme whose activity is also modulated by n-3 PUFAs.…”

Phospholipase D activation in fibroblast membranes by the α and β isoforms of protein kinase C

“…Regulation of the enzyme may occur by mechanisms involving G-proteins [24], Ca2+ [4,5], unsaturated fatty acids [6], and PKC . Much attention has focused on the role of PKC in the regulation of PLD.…”