Regulation of Brain Glycosylphosphatidylinositol-Specific Phospholipase D by Natural Amphiphiles

Brain glycosylphosphatidylinositol-specific phospholipase D (GPI-PLD)-catalyzed conversion of amphiphilic form of Zn²⁺-glycerophosphocholine cholinephosphodiesterase (Amp-GPC PDE) into hydrophilic form was investigated in the presence of natural amphiphiles. Monoacylglycerols enhanced considerably the conversion by GPI-PLD of Amp-GPC PDE to hydrophilic form, with the enhancing effect of monoacylglycerols being dependent on the size of acyl group (C₈–C₁₈). Whereas the maximal enhancement of GPI-PLD action was the greatest with monodecanoylglycerol, the concentration (EC₅₀) required to achieve 50% maximal effect was the smallest for monomyristoyl- or monopalmitoylglycerol. In addition, monolaurylglycerol or its alkyl analogue, monododecylglycerol, showed a remarkable decrease in enhancing effect at high concentrations (>1 mM). Presence of double bond in acyl chain, as exemplified by monooleoylglycerol or mono-11-eicosenoin, further enhanced the conversion by GPI-PLD. Meanwhile, lysophosphatidylcholine (IC₅₀, 25 M) and phosphatidic acid (IC₅₀, > 100 M), ionic amphiphiles, inhibited the GPI-PLD activity, which was determined in the presence of monooleoylglycerol as a detergent. From these results, it is suggested that the activity of GPI-PLD in vivo system may be regulated by natural amphiphiles.