Hexadecylphosphocholine and 2-modified 1,3-diacylglycerols as effectors of phospholipase D

Phospholipase D and its application in biocatalysis

“…The molecular mechanism of this so-called interfacial activation has mainly been analyzed on secretory phospholipase A 2 (Gelb et al 1995), whereas this phenomenon is less considered in studies on PLD. While the activation of PLD by interfaces is reported for micelle-forming substrates (Lambrecht & Ulbrich-Hofmann 1992, Dittrich et al 1998, Shnigir & Kisel 2004, the quality of interface is emphasized by studies on membranes with structural disturbances (Dorovska-Taran et al 1996).…”

“…PG, PS and PE are produced by transphosphatidylation even on an industrial scale. Also, alkylphosphate esters, such as the antitumor agent hexadecylphosphocholine, are substrates for PLD (Dittrich et al 1998). The degree of unsaturation of fatty acids in phospholipids influences the substrate specificity of PLD (Abousalham et al 1997).…”

Hexadecylphosphocholine inhibits phosphatidylcholine synthesis via both the methylation of phosphatidylethanolamine and CDP-choline pathways in HepG2 cells

“…Surprisingly, in the absence of PC/oleate liposomes, the addition of 100 lM HePC markedly increased soluble CT activity. HePC is a nonbilayerforming lipid and so in the assay mixture it must be as micelles [10], which could act as a system for reconstituting inactive soluble CT, thus increasing the enzyme activity.…”

“…However, a clear mechanism of action has not been established yet. An important mechanism for HePC-induced biological effects may be the inhibition of phospholipase C [8], phospholipase A 2 [9] or the activation of phospholipase D [10,11] which may be achieved by protein kinase C (PKC) dependent or independent mechanism, depending of the cell line investigated [11]. The toxicity of HePC may also be related to a disruption of calcium homeostasis [12].…”

Discrimination between the regioisomeric 1,2- and 1,3-diacylglycerophosphocholines by phospholipases

“…On the other hand, 1,3-PCs were found to be competitive inhibitors of PLD (Dittrich et al, 1998;Haftendorn et al, 2000) suggesting that the compounds are bound in the active site. Obviously, however, they are bound in a way that does not allow cleavage of the terminal phosphate ester bond.…”