Regulation of Phosphatidic Acid Metabolism by Sphingolipids in the Central Nervous System

Table 1

The table summarizes the principal effects produced by sphingolipids on PLA2, PLD, and LPPs enzymes.

	Sphingolipid effect	Ref.
PLA2	(i) Cer and C1P regulate eicosanoid synthesis through the activation of cPLA2𝛼 by favouring its transmembrane translocation and interaction with PtdCho.	[26, 39–42]
	(ii) Cer and SM influence sPLA2IIa fatty acid specificity by stimulating and inhibiting the release of C20:4 and C18:2, respectively.	[18, 37, 46]
	(iii) SM is a physiological inhibitor of sPLA2IIa, sPLA2V, and cPLA2.	[49–51]
	(iv) Cer and iPLA2𝛽 in association with mitochondria participate in endoplasmic reticulum stress-induced apoptosis.	[61, 64]
PLD	(i) Cer inhibits PLD activity by preventing its activation by PKCs and monomeric G proteins, by regulating its gene transcription or by direct effect on the catalytic core of the enzyme. Cer also abolishes the PtdOH/LysoPtdOH-stimulation of PLD.	[71–74]
	(ii) Sph and S1P regulate cellular proliferation by activation of PLD which stimulates DNA synthesis.	[75]
LPPs	(i) Sph inhibits the Mg^2+-dependent phosphatidate phosphohydrolase and LPPs activities, increasing the accumulation of PA relative to DAG.	[76, 77, 80]
	(ii) Cer increases the specific activity of LPPs thus reducing the mitogenic activity of their substrates PthOH and S1P.	[71]
	(iii) LPPs modulate responses mediated by S1P or LysoPthOH by regulating their extracellular availability as ligands and by controlling the accumulation of bioactive lipid phosphates downstream of G-protein receptor activation.	[81]