Phosphatidic acid , differences

The rate of production of DAG in the cell does not occur linearly with time, but rather it is biphasic. The first peak is rapid and transient and coincides with the formation of IP3 and the release of Ca2+ this DAG is therefore derived from the PI-PLC catalyzed hydrolysis of phosphatidylinositols [1]. There is then an extended period of enhanced DAG production that is now known to be derived from the more abundant phospholipid phosphatidylcholine (PC), which has a different composition of fatty acid side chains [9]. Although DAG may be generated directly from PC through the action of PC-PLC, it can also be formed indirectly from PC. In this pathway, PC is first hydrolyzed by PLD to give choline and phosphatidic acid, which is then converted to DAG by the action of a phos-phatidic acid phosphatase [10,11 ]. 

In the first phase of phospholipid synthesis from glyc-erol-3-phosphate to phosphatidic acid, the pathways in E. coli and eukaryotes are very similar (see fig. 19.2). The major difference is that one additional pathway exists for generation of phosphatidic acid from dihydroxyacetone phosphate, an intermediate in glycolysis. Once phosphatidic acid is made, it is rapidly converted to diacylglycerol or CDP-diacylglycerol (see fig. 19.2) both of which are intermediates for the biosynthesis of eukaryotic phospholipids. 

Lipid synthesis is unique in that it is almost exclusively localized to the surface of membrane structures. The reason for this restriction is the amphipathic nature of the lipid molecules. Phospholipids are biosynthesized by acylation of either glycerol-3-phosphate or dihydroxyacetone phosphate to form phosphatidic acid. This central intermediate can be converted into phospholipids by two different pathways. In one of these, phosphatidic acid reacts with CTP to yield CDP-diacylglycerol, which in bacteria is converted to phosphatidylserine, phosphatidylglycerol, or diphos-... 

Nolte and co-workers synthesized three different stereoisomers of a novel phosphatidic acid analogue bearing two phosphate groups, 26a, 26b and 26c. They examined the aggregation behavior of these lipids in their aqueous suspensions and also studied their fusion and fission processes upon vesicle formation [63],... 

In the bacterial PI-PLC structures, the top of the barrel rim has several hydrophobic residues that are fully exposed to solvent and poorly defined in the crystal structures (implying significant mobility). The active site of PI-PLC is accessible and well-hydrated, and these mobile elements at the top of the barrel offer a different motif for interactions of the protein with phospholipid interfaces. The PI-PLC from B. thuringiensis (nearly identical in sequence to the enzyme from B. cereus whose crystal structure was determined) exhibits the property of interfacial activation, where enhanced activity is observed when the substrate PI is present in an interface compared to monomeric substrate (Lewis et al., 1993). However, other non-substrate lipids such as phosphatidylcholine (PC), phosphatidic acid (PA), and other anionic lipids have an effect on the activity of PI-PLC toward both substrates PI and water-soluble cIP (Zhou et al., 1997). In particular, the presence of PC enhances the catalytic activity of... 

The practice has been established of naming the different phosphoaminolipides phospholipides. But what the commission proposed to name phospholipides are most currently termed phosphatidic acids. 

Group designations of PLAiS are now required as new PLAjS have been discovered and known enzymes have been better characterized. Previously, two phosphatidic acid (PA)-preferring and PA-selective PLAjS have been identified and characterized [4, 16]. However, this nomenclature is no longer appropriate, because the observed substrate specificities do not reflect the structural aspects of the enzymes, and there are at least two phosphatidic acid-preferring PLAjS with completely different structures [4, 16]. 

Polar head exchanges rely on the wide substrate specificity of PLD from bacterial sources. From low molecular weight primary alcohols to large secondary ones, many structurally diverse compounds have been shown to be substrates for PLD with different yields and selectivity (path c). The hydrolysis compound phosphatidic acid (PA) will be present as a by-product. 

Abrahamson et at (34) observed a similar departure from the latter sequence of calcium and magnesium in their reaction with a phosphatidic acid dispersion at pH 7. Shah and Schulman (35) also found a higher tendency of Ca2+ than Mg2+ to interact with a monolayer of dicetyl phosphate at pH 5.6 as judged by surface pressure measurements although surface potential measurements indicated little difference between the two ions as did potential measurements on phosphatidyl serine mem-... 

Figure 1. Effect of donor particle concentration on the initial rate of lipid transfer. The computer-drawn curves are based on the kinetic model by Van den Besselaar et al. (1975) for protein-catalyzed phospholipid exchange. The kinetic constants are for, the transfer of phosphatidylcholine from liposomes containing 12 mol% phosphatidic acid to liposomes containing 2 mol% phosphatidic acid. The three curves represent three different acceptor concentrations indicated above the appropriate curves.

The effect of different phospholipid head groups on the protein-stimulated transfer by phosphatidylcholine- and phosphatidylinositol-specific proteins has been studied. Contradictory results were obtained for the effect of acidic phospholipids on the transfer of phospholipid by the phosphatidylcholine exchange protein from beef liver. DiCorleto et al. (1977) used small unilamellar vesicle-mitochondria and small unilamellar vesicle-multilamellar vesicles to study the effect of varying amounts of acidic phospholipids incorporated into phosphatidylcholine donor vesicles. Up to 20 mol% phosphatidic acid or phosphatidylinositol in the donor was found to stimulate the transfer of phosphatidylcholine in both assay systems. Wirtz et al. (1979) and Hellings et al. (1974) found different results for the phosphatidylcholine exchange protein with unilamellar and multilamellar vesicles. In these assays, the incorporation of acidic phospholipids (phosphatidic acid or phosphatidylinositol) into the donor particles had an inhibitory effect on the rate of phosphatidylcholine transfer. 

---