Ceramide 1-phosphate

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. 

McClure, C.K. and Mishra, P.K., Synthetic studies toward the preparation of phosphonate analogs of sphingomyelins and ceramide 1-phosphate using pentacovalent organophosphorus methodology, Phosph., Sulf. Silic., Ill, 709, 1996. 

Nakamura H., Hirabayashi T., Shimizu M., and Murayama T. (2006). Ceramide-1 -phosphate activates cytosolic phospholipase A2a directly and by PKC pathway. Biochem. Pharmacol. 71 850-857. 

Chalfant, C. E. and Spiegel, S. (2005). Sphingosine 1-phosphate and ceramide 1-phosphate Expanding roles in cell signaling. /. Cell Sci. 118(Pt 20), 4605M612. 

A sphingoid analog of phosphatidic acid, ceramide-1-phosphate, has recently emerged as potent bioactive agent. Recent studies defined new biologic functions for this lipid related to control of numerous aspects of cell physiology, which include cell survival and mammalian inflammatory responses (26). 

Ceramide formed in mammalian systems is metabolized to sphingomyelin, glycosphingolipids, and ceramide 1-phosphate by the actions of sphingomyelin synthase, glucosylceramide synthase, and ceramide kinase on ceramide, respectively. Ceramide synthesized in the endoplasmic reticulum is transported to the Golgi apparatus for synthesis of complex sphingolipids (93). Sphingomyelin is synthesized from ceramide by transfer of the... 

Kihara A, Mitsntake S, Mizntani Y, Igarashi Y. Metabolism and biological fnnctions of two phosphorylated sphingolipids, sphingosine 1-phosphate and ceramide 1-phosphate. Prog. Lipid Res. 2007 46 126-144. 

Marcu AC, Chalfant CE. Ceramide 1-phosphate, a new bioactive sphingohpid in regnlating cell signaling. Fntnre Lipidol. 2007 2 75-84. 

A novel regioselective, convenient and efficient synthesis of model D-erythro-sphingosine 1-phosphate (87) and D-erythro-ceramide 1-phosphate (88) has been presented. ... 

In a later paper it was established that ceramide 1-phosphate was released from the GIPLs by the PLD from rat blood plasma.17... 

R. M. de Lederkremer, C. Lima, and M. C. Vila, Ceramide 1-phosphate is released from a glycoinositol-... 

Model studies for the syntheses of phosphonate analogues of sphingomyelin and ceramide 1-phosphate from pentaco-ordinate phospholene 112 have been reported. Compound 112 undergoes ring opening on reaction with dialkyl azodicarboxylates to give 113 which reacts with sodium borohydride stereoselec-tively to give predominantly trans- 4 (Scheme 6). The preparation has been described, via phosphorus chloride methods, of the potential haptens 115 for the production of phospholipase A2-like catalytic antibodies. ... 

Gomez-Munoz, A. (2006). Ceramide 1-phosphate/ceramide, a switch between life and death. Biochim Biophys Acta 1758, 2049-2056. 

Gomez-Munoz, A., Kong, J. Y., Salh, B., and Steinbrecher, U. P. (2004). Ceramide-1-phosphate blocks apoptosis through inhibition of acid sphingomyelinase in macrophages. J Lipid Res 45, 99-105. 

Phosphate (Sphingosine 1-Phosphate, SIP Ceramide 1-Phosphate, CerIP) -Fatty acid (1-O-Acyt-Ceramide) -Phosphocholine (Sphingomelin)... 

Fig. 12. Some signaling targets and pathways affected by sphingolipid backbones that are metabolically interrelated. PKA, protein kinase A PDKl, 3-phosphoinositide-dependent kinase 1 SDKl, sphingosine-dependent kinase 1 PKC, protein kinase C PPl, protein phosphatase 1 PP2A, protein phosphatase 2A aSMase, acid sphingomyelinase PLA, phospholipase Aj SIP, sphingosine-l-phosphase MATIA, methionine adenosyl-transferase (liver specific) SFl, steroidogenic factor 1. The biophysical properties of ceramides and ceramide 1-phosphates may play important roles in membrane structure, including tendencies to form rafts, membrane curvature, and leakiness.

Tetra-O-acetyl-P-D-gluco- and -galactopyranosyl H-phosphonates were converted into citronellyl and dolichyl glycosyl phosphates by reaction with the respective alcohols, followed by oxidation and deacetylation,and dolichyl p-D-mannopyranosyl phosphate was prepared by reaction of a protected a-D-manno-pyranosyl bromide with dolichyl phosphate. Ceramide-1-phosphate sugars, e.g., P-D-Glc/>-0P03-Cer, a new type of glycophospholipid, have been obtained... 

Sphingolipid phosphate analogues bearing 7-(diethylamino)-coumarin (56) and 4-bromo-5-hydroxy-2-nitrobenzhydryl (57) groups in a photolabile ester bond have been synthesized by Bittman and co-workers. " The ability of caged ceramide 1-phosphate (CIP, (58)) conjugates to deliver CIP into mammalian cell cultures on exposure to visible light has been assessed, too. 

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