Phosphatidic acid phosphatase and

DAG species are derived from three main routes (1) PLC-mediated hydrolysis of phospholipids (2) phosphatase-mediated hydrolysis of phosphatidic acid (PA) and (3) lipase-mediated hydrolysis of triacylglycerol (TAG) species (Fig. 2). Targeted lipidomic analyses show that the fatty acid compositions of the DAGs formed by these various routes reflect the composition of the parent lipid (Fig. 5). In particular, those derived from inositol phospholipids are highly enriched in... 

The synthesis of triacylglycerol takes place in the endoplasmic reticulum (ER). In liver and adipose tissue, fatty adds in the cytosol obtained from the diet or from de novo synthesis of palmitic add become inserted into the ER membrane. The reactions are shown in Fig. 13-10. Membrane-bound acyl-CoA synthetase activates two fatty acids, and membrane-bound acyl-CoA transferase esterifies them with glycerol 3-phosphate, to form phosphatidic acid. Phosphatidic acid phosphatase releases phosphate, and in the membrane, 1,2-diacylglycerol is esterified with a third molecule of fatty acid. 

A concise and straightforward hydrolytic kinetic resolution of ( ) 1,1-difluoro-3,4-epoxybutylphosphonate (453) using a chiral Salen-Co complex was employed as a key step to obtain enantiomeric diols in 99% ee as important intermediates. The enantiomerically homogenous l,l-difluoro-2,3-di-hydroxypropylphosphonates (454) and (455) were converted by stereoselective esterification and deprotection into the novel phosphatase resistant analogues of lysophosphatidic acid and phosphatidic acid (456) and (457), respectively (Figure 86). ° ... 

Kai M, Wada I, Imai S, Sakane F, Kanoh H (1996) Identification and cDNA cloning of 35-kDa phosphatidic acid phosphatase (type 2) bound to plasma membranes. Polymerase chain reaction amplification of mouse H2O2-inducible hic53 clone yielded the cDNA encoding phosphatidic acid phosphatase. J Biol Chem 271 18931-18938... 

NCEP National Cholesterol Education Program NHANES National Health and Nutrition Examination Survey NNT Number needed to treat PAP Phosphatidic acid phosphatase... 

The product is phosphatidic acid, itself an important substance (see page 31) and the starting point for the phosphatides and related lipids. The conversion of phosphatidic acid into triglyceride demands first the removal of the phosphate through hydrolysis by the enzyme phosphatidic acid phosphatase (an irreversible reaction). The product is diglyceride, which can react with a final fatty acyl-CoA to yield triglyceride (14,15) ... 

Fig. 6.15 Formation and function of diacylglycerol. The figure schematically shows two main pathways for formation of diacylglycerol (DAG). DAG can be formed from PtdlnsP2 by the action of phospholipase C (PL-C). Another pathway starts from phosphatidyl choline. Phospholipase D (PL-D) converts phosphatidyl choline to phosphatidic acid (Ptd), and the action of phosphatases results in DAG. Arachidonic acid, the starting point of biosynthesis of prostaglandins and other intracellular and extracellular messenger substances, can be cleaved from DAG. PKC protein kinase C Ptdlns phosphatidyl inositol.

Figure 2.13. Histamine H,-receptor-mediated inositol phospholipid hydrolysis. Stimulation of H,-receptors leads to activation of a phospholipase C. probably via a guanine-nucleotide regulatory protein (N). which catalyses the hydrolysis of phosphatidylinositol 4.5 -bisphosphate (PIP2) to give inositol trisphosphate (IP3) and 1,2-diacylglycerol (DG). IP3 is then broken down by phosphatases to eventually yield free myo-inositol. Lithium ions can inhibit the conversion of inositol 1-phosphate (IP,) to myo-inositol. Free inositol then interacts with CDP-diacylglycerol,formed by a reaction between phosphatidic acid (PA) and CTP, to yield phosphatidylinositol (PI). Phosphorylation of PI by kinases completes the lipid cycle by reforming PIP2. Modified from [147,148].

Fig. 5. Pathway depicting how flux through phosphatidylcholine (product of reaction 3) can promote acyl group diversity in plant triacylglycerols. Production of 18 2 (boxed) at the sn-2 position and its transfer to TG is used as a sample modification. Other fatty acid alterations may be substituted. Enzymes 1, glycerol-3-phosphate acyl-CoA acyltransferase and lysophosphatidic acid acyl-CoA acyltransferase 2, phosphatidic acid phosphatase 3, diacylglyceroliCDP-aminoalcohol aminoalcoholphosphotransferase 4, 18 l-desaturase or other fatty acid modifying enzyme 5, phosphlipid diacylglycerol acyltransferase 6, diacylglycerol acyltransferase 7, acyl-CoA phosphatidylcholine acyltransferase or phospholipase plus acyl-CoA synthetase.

Fig. 2. Biosynthesis of phosphatidic acid (PA) occurs on both the endoplasmic reticulum (ER) and the outer membrane of mitochondria. The abbreviations are ACS, acyl-CoA synthetase, GPAT, glycerol-3-P acyltrans-ferase AGPAT, l-acylglycerol-3-P acyltransferase PP, phosphatidic acid phosphatase (lipin) PC, phosphatidylcholine PE, phosphatidylethanolamine TG, triacylglycerol.

Kudlaez, E. M, Navarro, H. A., Eylers, J. P., Dobbins, S. S Lappi, S. E., and Slotkin, T. A. (1989). Selective linkage of P-adnenergic receptors to functional responses in developing rat lung and liver Phosphatidic acid phosphatase, ornithine decaiboxylasc and lung liquid reabsorption. J. Dev. Physiol. 12, 129-134. 

Once phosphatidic acid is formed it can be converted to diacylglycerol by phosphatidic acid phosphatase. This is a key enzyme which, although catabolic, is involved in synthetic reactions-namely triacylglycerol, phosphoglyceride and glycosyl-glyceride formation. Phosphatidic acid phosphatase activity has been reported in various animal (Bell... 

The breakdown of glycerophospholipids is catalysed by a series of phospholipases designated A, B, C and D depending on their positions of attack (Fig. 11.16). In addition, phosphatidic acid phosphatase is important, but this has already been dealt with (Section 11.2.1). Two phospholipase A specificities are recognized and these are named Ai and A2 depending on the position of the ester hydrolysed in the diacylphosphoglyceride. Phospholipase B is the name usually used for an enzyme which is a... 

Fig. 10. Mechanism explaining the acylation of -glycerol 3-phosphate in the envelope membranes. El, Acyl-CoA synthetase E2, acyl-CoA in-glycerol 3-phosphate acyltransferase E3, acyl-CoA acyl-sn-glycerol 3-phosphate acyltransferase E4, phosphatidic acid phosphatase. El, E3, and E4 are firmly bound to the chloroplast envelope. E2 is probably loosely bound to the envelope and is released into the medium during the isolation (see Fig. 12) (reproduced from Douce and Joyard, 1979a, by permission).

Figure 2. The so-called canonical phosphoinositide pathway . The continuous phosphorylation/dephosphorylation reactions allow a steady-state level of Ptdins, PtdIns(4)P and PtdIns(4,5)P2 in the plasma membrane (PM). Cleavage of PtdIns(4,5)P2 by phospholipase C (PLC) generates the two well-known second messengers, inositol 1,4,5-trisphosphate (Ins(l,4,5)P3) and diacylglycerol (DAG). Besides its role as a protein kinase C (PKC) activator, DAG can be phosphorylated to phosphatidic acid (PA). The resynthesis of Ptdins from inositol and PA occurs mainly in the endoplasmic reticulum (ER). PPi, inorganic phosphate. PA-Pase, phosphatidic acid phosphatase. PA-TP, phosphatidic acid transport protein. PtdIns-TP, phosphatidylinositol transport protein. CDP-DAG, cytidine diphosphate-diacylglycerol. CMP, CDP and CTP, cytidine mono-, di- and triphosphate, respectively.

Furthermore it was possible to demonstrate the presence in the intestine of all the enzymes required for these steps. Fatty acid-coenzyme A synthesis was demonstrated by Ailhatjd et al. (1962) and by Clark and Hubscher (1960). The involvement of phosphatidic acid could be demonstrated by isolation of radioactive phosphatidic acid in intestinal preparations incubated with radioactive fatty acids or phosphoric acid (Johnston and Bearden 1960). Furthermore, a significant dilution effect in the synthesis of glycerides from C-fatty acids occurred by the addition of phosphatidic acid (Clark and Hubscher 1961). Phosphatichc acid phosphatase activity in the intestine was reported by Coleman and Hubscher (1962) and by Johnston and Bearden (1962). Finally, the conversion of diglyceride into triglycerides by the addition of a fatty acid — Co A was shown to take place in the intestine by Clark and Hubscher (1961). 

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