Phospholipases A, PLA

The classification of the phospholipases, based on their site of attack, is given in Fig. 2. The phospholipases A (PLAs) are acyl hydrolases classified according to their hydrolysis of the 1-acyl ester (PLA,) or the 2-acyl ester (PLA2). Some phospholipases will hydrolyze both acyl groups and are called phospholipase B (PLB). In addition, lysophospholipases... 

A variety of second messengers have been implicated in auxin signaling including phosphatidylinositol, calcium, and the products of phospholipase A (PLA) enzyme. Since most of these reports have been in the literature for some time, they will not be discussed here (see [47] for review). Recent reports have provided additional evidence for a role for PLA in auxin action. Earlier studies by Andre and Scherer [48] showed that auxin treatment resulted in an increase in PLA activity in a number of plant species suggesting that a product of this enzyme functions as a signaling molecule. Consistent with this possibility, inhibitors of mammalian PLA inhibit auxin-induced hypocotyl elongation in... 

Phospholipases A (PLA ) are a diverse class of enzymes catalysing the hydrolysis of the sn-2 ester bond of phospholipids. This growing superfamily of lipolytic enzymes has at least 19 mammalian enzyme members identified to date (Balsinde et ah, 2002). The PLA enzymes have recently been systematically classified on the basis of their nucleotide and amino acid sequences (Dennis, 1997 Six and Dennis, 2000). 

Research on structural modification of PLs to achieve the aforementioned nutritional and functional properties has increased prominently. The structural modification of PLs can be done enzymatically using phospholipases and lipases. Phospholipase A (PLAj) cleaves the fatty acid at the sn-l position, while Phospholipase A (PLA ) cleaves the fatty acid at the sn-2 position. Phospholipase C (PLC) hydrolyses the phosphodiester bond between the glycerol backbone and phosphate. On the other hand, phospholipase D (PLD) hydrolyses the phosphodiester bond between the phosphate and the head group. Lipases can also be used to modify the fatty acid composition at sn-l and sn-2 positions of phospholipids. Guo and co-workers (2005) and Nieuwenhuyzen and Thomas (2008) have provided a detailed review on enzymatic modification of phospholipids for functional applications and human nutrition. 

Biological/Medical Applications Dyed polymer microparticles purifying oligonucleotides regulating meiosis as a substrate for measuring lysophospholipase D (lysoPLD) activity, " " phospholipases A (PLA) activity ... 

Two possible pathways for the biosynthesis of 2-AG have been proposed (1) a phospholipase C (PLC) hydrolysis of membrane phospholipids followed by a second hydrolysis of the resulting 1,2-diacylglycerol by diacylglycerol lipase or (2) a phospholipase Ai (PLA,) activity that generates a lysophospholipid, which in turn is hydrolyzed to 2-AG by lysophospholipase C (Fig. 5) (Piomelli, 1998). Alternative pathways may also exist from either triacylglycerols by a neutral lipase activity or lysophosphatidic acid by a dephosphorylase. The fact that PLC and diacylglycerol lipase inhibitors inhibit 2-AG formation in cortical neurons supports the contention that 2-AG is, at least predominantly, biosynthesized by the PLC pathway (Stella, 1997). However, a mixed pathway may also be plausible. 

PLA phospholipase A SCAD short chain acyl-CoA dehydrogenase... 

PARK Beta adrenergic receptor kinase PLA Phospholipase A... 

Fig. 1. Targeted lipidomics of anandamide metabolism. Postulated pathways of anandamide metabolism. Abbreviations PC, phosphatidylcholine PE, phosphatidylethanolamine NAT, JV-acyl transferase LPA, lysophosphatidic acid PA, phosphatidic acid NAPE, jV-acyl-phosphatidylethanolamine Lyso-NAPE, l-lyso,2-acyl-OT-glycero-3-phosphoethanolamine-JV-acyl ABHD-4, a//3 hydrolase-4 GP-anandamide, glycerophospho-anandamide PAEA, phospho-anandamide PLA, phospholipase A NAPE-PLD, NAPE phospholipase D PLC, phospholipase C FAAH, fatty acid amide hydrolase P, phosphatase COX, cyclooxygenase LOX, lipoxygenase CYP450, cytochrome P450 PDE, phosphodiesterase.

Fig. 2. Targeted lipidomics of 2-AG metabolism. Postulated pathways for 2-AG metabolism. Abbreviations PLC, phospholipase C DAG, diacylglycerol DGL, diacylglycerol lipase MGL, monoacylglycerol lipase PLA, phospholipase A AT, acyltransferase TAGL, triacylglycerol lipase PIP2, phosphatidylinositol bisphosphate ABHD-6/12 hydrolase lyso-PL, lysophospholipid lyso-PA, lysophosphatidic acid PA, phosphatidic add P, phosphatase COX, cydooxygen-ase LOX, lipoxygenase CYP450, cytochrome P450 CDP, cytidine diphosphate.

PLA, PLA2, PLC, PLD Phospholipases A, A2, C and D PLN Peripheral lymph node PLNHEV Peripheral lymph node... 

Membrane-associated Phosphatidic Acid-selective Phospholipase A s (mPA-PLAi and mPA-PLA, ... 

Abbreviations used are as follows AR, adrenergic receptor [Ca ]i, intracellular calcium CEC, chloroethylclonidine DAG, diacylgiycerol EPI, epinephrine CNS, central nervous system HEK 293, human embryonic kidney 293 cells IPTG, isoproply-P-D-thiogalactoside InsP, inositol phosphate IP, inositol (1,4,5) trisphosphate NE, norepinephrine PI, phosphatidyl inositol PLA, phospholipase A, PLC, phospholipase C PLD, phospholipase D PKC, protein kinase C rMTC 6-23, rat medullary thyroid carcinoma cells VDCC, voltage-dependent Ca chaimel. 

The phospholipases A, (PLAjS) comprise a large group of 1-acyl hydrolases, some of which also degrade neutral lipids (lipases) or remove the acyl group at position 2 in addition to that at position 1 (PLB), and thus must have lysophospholipase activity. Where the enzyme appears to show low selectivity for the sn-l or sn-2 position, the term phospholipase A is used. The term phospholipase B should be restricted to those enzymes where the mechanism involves minimal accumulation of lysophospholipid product. In this section, we consider various enzymes of the PLA type that do not fit a more precise definition in terms of acyl chain selectivity. 

Two PLAs have been purified from Escherichia coli based on their differential sensitivity to treatment with detergents [2]. A detergent-insensitive enzyme is localized in the outer membrane, whereas a detergent-sensitive enzyme is found on the cytoplasmic membrane and in soluble fractions. The outer membrane enzyme, known as outer membrane phospholipase A, has broad substrate specificity and demonstrates PLA, PLAj, lysophospholipase A, and lysophospholipase Aj activity as well as activity for hydrolyzing monoacylglycerols and diacylglycerols. The crystal structure allows a more detailed discussion of an integral membrane phospholipase [12]. 

PKC, protein kinase C T, increases ERK, extra-cellular-signal related kinase PLA, phospholipase A PGE, prostaglandin E PLC, j ospholipase C PKA, protein kinase A. 

FRET probes have not only been generated to measure the phospholipase activity but to study its substrate specificity as well. Several substrates of PLA2 with a variety of head groups and labeled with a BODIPY dye and a Dabcyl quencher were created by Rose et al. and tested against different PLAs in cells to determine substrate specificity and intracellular localization [137], The specificity of PLA2 isoforms towards the number of double bonds in the sn2 position was evaluated with a small series of PENN derivatives. It was demonstrated that the cytosolic type V PLA2 preferred substrates with a single double bond [138],... 

Alternatively, the release of platelet phospholipid AA is mediated by the activation of phospholipase Aj (PIA) coupled to PLC, intracellular Ca rise and protein kinase C (PKC) and tyrosine kinase-mediated protein phosphorylations (23,24) and/or by the activation of PLA that is not coupled to these events in platelets (25-29). Furthermore, the hydrolysis of phosphatidic acid (PA) by a PA-specific PLAj may also contribute to eicosanoid synthesis (30,31). It is evident that the differential sensitivity of platelets to multiple agonists and their signals, have contributed to the complexity in understanding the regulation of PLAj. 

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