Transphosphatidylation

For example, lysophosphatidylserine obtained through phospholipase D-mediated transphosphatidylation and phospholipase A or 5/1-1 positional specific lipase-mediated partial hydrolysis seemed to be the most effective chemical form in delivering DHA into brain. 

P. Wang, M. Schuster, Y.-F. Wang, and C.-H. Wong, Synthesis of phospholipid-inhibitor conjugates by enzymatic transphosphatidylation with phospholipase D, J. Am. Chem. Soc., 115 (1993) 10487-10491. 

Phospholipase D. An improved biosurfactant and emulsifier is made from lecithin by phospholipase D. The enzyme transphosphatidylates lecithin, converting most of the phosphatidylcholine and phophatidyl-ethanolamine to phosphatidylglycerol (49). 

Synthesis of CNDAC and DPP-CNDAC was performed as described previously (16, 17). Briefly, a phosphatidyl group was introduced into CNDAC through transphosphatidylation from l,2-dipalmitoyl-3-sn-glycerophosphocholine by using phospholipase D. 

For example, an isozyme of glutathione-S-transferase will also catalyze the fatty acid ethyl-ester synthase reaction, leading to the formation of ethyloleate from oleic acid and ethanol (Bora et al. 1989). Also, phospholipase D catalyzes the transphosphatidylation of phosphatidylcholine with ethanol to form phosphatidylethanol (Kobayashi and Kanfer 1987). The active site requirements and kinetics of the hydrolases or transferases that catalyze these ethylation reactions are not well understood. The elucidation of mechanisms and active site structures for enzyme-catalyzed... 

Kobayashi, M., and Kanfer, J.N. Phosphatidylethanol formation via transphosphatidylation by rat brain synaptosomal phospholipase D. JNeurochem 48(5) 1597-1603, 1987. 

Petersen G, Hansen H.S (1999) N-acylphosphatidylethanolamine-hydrolysing phospholipase D lacks the ability to transphosphatidylate. FEBS Lett 455 41 4... 

Keywords Phospholipids, Phospholipases, Transphosphatidylation, Organic phosphates, Diacylglycerol. 

From PC transphosphatidylation gives the PX modified in its polar head. 

Scheme 5. Phospholipids with polar heads of various types obtained by PLD catalysed transphosphatidylation from PC and primary alcohols (PI = phosphatidyl-)...

The attempt to obtain structural analogues to phosphatidyl inositols failed. Trihydroxy-cyclohexanes proved not to be substrates of such enzymes, like myoinositol itself and derivatives [151]. The PLD isolated from spinach leaves was reported to be able to give PI as a transphosphatidylation product from PC and inositol [94]. To our knowledge no further exploitation of this method has followed the original article. Other authors have reported the formation of... 

Table 2. Comparison of kinetic and selectivity data in the PLD catalyzed transphosphatidylation reaction of PC with primary and secondary alcohols (PLD from S. PMF, ethyl acetate/ace-tate buffer pH 5.5,1 mol L alcohol, 150 mmolL PC, 25 °C, 30 U/g substrate) t, . = time in min of consumption of half of the starting substrate. tf= disappearance of PC (HPLC) [146] ...

Table 3. Conversion and selectivity of PLD catalyzed transphosphatidylation of different PL in an emulsion system (PLD from S. PMF) [43]...

Phospholipases are very versatile enzymes which allow the transformation of inexpensive natural products into highly valuable compounds like specific structurally defined phospholipids, organic monophosphates or diphosphates and DAG with the natural absolute configuration. Of particular synthetic utility is PLD from bacterial sources which is able to effect the phosphoryl transfer in a water-containing biphasic system. PLD shows a wide substrate specificity for both the polar head and the alcohol acceptors as well as for the lipophilic part of the molecule. The enzyme behaves like a generic phosphodiesterase with broad substrate specificity and high transphosphatidylation ability. The molecular basis of this behavior should become clear by inspection of the three-dimensional structure and comparison with other phosphoric acid ester hydrolytic enzymes. The crystal structure of this enzyme has not been elucidated. The potential of the many different PLD from plants which show peculiar substrate specificity should allow one to expand the synthetic utility to the hydrolysis-synthesis of natural and unnatural phosphatidylinositols. 

Okahat, Y., Nukura, K., and Ijiro, K., Simple transphosphatidylation of phosphohpids catalysed by a lipid-coated phospholipase D in organic solvents, J. Chem. Soc. Perkin Trans. /, 919-925, 1995. 

Possible transphosphatidylation products from PC and secondary alcoh 1... 

Enzymatic conversion of PC to PX via transphosphatidylation reaction of PC has thus become an accepted industrial method for the modification of phospholipids at their polar head. The more frequent and simple application of the biocatalyst consists of the direct use of the culture broth in a biphasic system. The pH optimum and cofactor requirements for some of the most common PLD... 

Phospholipase D (EC 3.1.4.4) is a lipolytic enzyme that hydrolyzes the terminal phosphodiester bond on PLs. Due to its ability to transfer the phosphatidyl moiety of glycerophospholipids to various alcohols (transphosphatidylation), PLD is also used to synthesize PLs with desired head groups that are poorly accessible via the chemical route (Figure 23.4). This ability has been utilized for the synthesis of natural PLs that are rare in nature, such as PG and PS. Novel types of PLs (phosphatidyl-X) have also been synthesized via PLD-mediated transphosphatidylation to add the amphiphilic properties of PLs to the acceptor compounds. These reactions are typically carried out in biphasic systems with water (containing PLD or a hydrophilic alcohol acceptor) and an organic solvent such as chloroform, ether, ethyl acetate, benzene, or toluene. 

Juneja et al. reported transphosphatidylation mediated by PLD in detail. PG, PE, and PS were synthesized from lecithin or PC by PLD [26-30]. PG, PE, and PS were prepared in quantity by chemoenzymatic synthesis under optimized conditions by... 

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