Lipid Phosphate Phosphohydrolases

Lipid phosphate phosphohydrolases (LPPs), formerly called type 2 phosphatidate phosphohydrolases (PAP-2), catalyse the dephosphorylation of bioactive phospholipids (phosphatidic acid, ceramide-1-phosphate) and lysophospholipids (lysophosphatidic acid, sphingosine-1-phosphate). The substrate selectivity of individual LPPs is broad in contrast to the related sphingosine-1-phosphate phosphatase. LPPs are characterized by a lack of requirement for Mg2+ and insensitivity to N-ethylmaleimide. Three subtypes (LPP-1, LPP-2, LPP-3) have been identified in mammals. These enzymes have six putative transmembrane domains and three highly conserved domains that are characteristic of a phosphatase superfamily. Whether LPPs cleave extracellular mediators or rather have an influence on intracellular lipid phosphate concentrations is still a matter of debate. 

SIP is formed from sphingosine by sphingosine kinases (SphKs). Degradation of SIP occurs either reversibly by lipid phosphate phosphohydrolases (LPPs) and SIP phosphatases (SPPs), or irreversibly by SIP lyase (SPL) (Fig. 1). The localization of SIP production is highly important since SIP plays a role both as extracellular mediator and as intracellular... 

Brindley, D.N. and Waggoner, D.W., 1998, Mammalian lipid phosphate phosphohydrolases,... 

Bergstrom, J., Kurtz, M.B. and Spiegel, S., 2000, Molecular cloning and characterization of a novel lipid phosphohydrolase that degrades sphingosine 1-phosphate and induces cell death, Proc. Nat. Acad. Sci U.S.A. 97 7859-7864. 

A phosphohydrolase activity cleaves the phosphate ester bond of phosphatidic acid forming 1,2 diacylglycerol, which may then enter its usual metabolic route the reaction goes both ways, and phosphatidic acid may be synthesized from 1,2 diacylglycerol by the action of a lipid kinase (Fig. 2.8). As mentioned, this two-way shunt plays havoc with the attempts to determine unequivocally whether 1,2 diacylglycerol and phosphatidic acid derive from the activation of PLC or PLD. ... 

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