Lipids lysophosphatidic acid

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. 

As in the case of anandamide, 2-AG is derived from the hydrolysis of complex membrane lipids. The direct precursors of 2-AG can either be 1-acyl, 2-arachidonoyl-diacylglycerols (DAGs) or 2-arachidonoyl-lysoglycerophospholi-pids (e.g., lysophosphatidic acid, LPA). 

AG can be converted back into complex lipid molecules by anabolic enzymes. This recycling process is mediated by MAG kinases (MAGK) and acyltransferases (AT) to generate 2-arachidonoyl-lysophosphatidic acid and DAG, respectively. In turn, these lipids can be then converted into glyceropho-spholipids or TAG (Fig. 2). 

Much attention has recently focused on lyso-formed phospholipids, including both glycerophospho-lipids such as lysophosphatidic acid (LPA) and lysosphingolipids such as sphingosine-1-phosphate (S-l-P) and sphingosylphosphorylcholine (SPC) (Figure 27.2), since they elicit diverse cellular... 

Murakami-Murofushi et al. further studied the lipid fraction of this myxomycete and succeeded in isolating novel lysophosphatidic acid (PHYLPA) (73) [39]. This compound, composed of cyclic phosphate and cyclopropane-containing hexadecanoic acid, inhibited more than... 

The compounds represented in this facsimile were as follows Nl, neutral lipids (cholesterol, triacylglycerol) PE, phosphatidylethanolamine PS, phos-phatidylserine PI, phosphatidylinositol PC, phosphatidylcholine Sph, sphingomyelin X, gangliosides, polyphosphoinositides, lysophosphatidic acids. The chromatography was done on silica gel G plates with chloroform-methanol-ester (65 35 31, v/v) as the solvent. 

The extraction of this lipid from a cellular preparation can be accomplished through the use of an acidified chloroform-methanol mixture as described earlier for isolation of the lysophosphatidic acids and other acidic phospholipids. The chloroform-rich phase represented the total lipid and can be studied further as described in the following section. 

Smyth SS, Sciorra VA, Sigal YJ, Pamuklar Z, Wang Z, Xu Y, Prestwich GD, Morris AJ (2003) Lipid phosphate phosphatases regulate lysophosphatidic acid production and signaUng in platelets studies using chemical inhibitors of lipid phosphate phosphatase activity. J Biol Chem 278 43214 3223... 

Das, A. K., Hajra, A. K. Quantification, characterization and fatty acid composition of lysophosphatidic acid in different rat tissues. Lipids 24 (1989) 329-333. 

Siess, W., Essler, M., Brandi, R. Lysophosphatidic acid and sphingosine 1-phosphate two lipid villains provoking cardiovascular diseases lUBMB Life 49 (2000) 67-71. 

Tokumura, A., Fukuzawa, K., Tsukatani, H. Effects of synthetic and natural lysophosphatidic acids on the arterial blood pressure of different animal species. Lipids 13 (1978)... 

Since phosphatidic acid serves as a precursor of phospholipids, galactolipids, and TGs, it is not surprising that its own synthesis has been reported in four plant compartments plastids, ER, mitochondria, and Golgi bodies. In each case, esterification of the first acyl group to the in-1 position of glycerol-3-phosphate is catalyzed by glycerol-3-phosphate acyltransferase. Lysophosphatidic acid acyltransferase then completes the synthesis by acylating the sn-2 position. However, plastidial and extraplastidial acyltransferases show distinct differences in structure and specificity. Analysis of these differences and the different compositions of plastid and non-plastid membranes led to the prokaryotic/ eukaryotic two-pathway scheme for plant lipid synthesis shown in Fig. 3. 

In the plastids, acyltransferases provide a direct route for entrance of acyl groups from ACP to membrane lipids. Since this is the standard pathway for phosphatidic acid synthesis in E. coli and cyanobacteria, both the enzymes of phosphatidic acid synthesis in plastids and the glycerolipid backbones they produce are termed prokaryotic . In both chloroplasts and non-green plastids, the glycerol-3-phosphate acyltransferase is a soluble enzyme that, unlike the E. coli enzyme, shows preference for 18 1-ACP over 16 0-ACP. The lysophosphatidic acid acyltransferase, which is a component of the inner envelope of plastids, is extremely selective for 16 0-ACP. The presence of a 16-carbon fatty acid at the... 

Ramwell and Shaw (1964) have recently tested many lipids with isolated rat uterus and their findings are summarized in Table III. Under the conditions used a lysophosphatidic acid (glycerol l-acyl-3-phosphate) had the greatest activity, while a cyclic acetal plasmalogen containing ethanolamine (glycerol l,2-0-hexadecylidene-3-phosphorylethanolamine) had very little. None of the phospholipids tested compared in potency with the prostaglandins. 

Sugiura, T., Nakane, S., Kishimoto, S., Waku, K., Yoshioka, Y., andTokumura, A. (2002)Lysophosphatidic acid, a growth factor-like lipid, in the sahva. The Journal of Lipid Research, 43, 2049—2055. 

The incorporation of [ C]glycerol and [ CJglycerol phosphate into lipids was studied by Barron and Stumpf (1962). The active fraction obtained from avocado Persea americana L.) fruit mesocarp was purified by density gradient centrifugation, and most of the activity was found in the microsomal fraction. The first product was PA [but analysis at early time points detected lysophosphatidic acid (LPA)], followed by monoacylglycerol, diacylglycerol, and triacylglycerol in that order. 

Figure 2. Effect of various lipids on DGAT activity in the 0.5% Triton X-100 extract. CL, cardiolipin G3P, glycerol-3-phosphate LPC, lysophosphatidylcholine ITS, lysophosphatidylserine LPA, lysophosphatidic acid.

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