Lysophospholipases activity

Two thioacyl protein thioesterases (APTs) have been identified. Unlike PATs, both are soluble proteins. Acylprotein thioesterase-1 (APTl) was purified from rat liver cytosol using palmitoylated G-protein a-subunit as a substrate (J.A. Duncan, 1998, 2002). This thioesterase, a 29-kDa monomeric protein, is likely to be the one involved in turnover of cytoplasmically disposed thioacyl groups of proteins. It displays both acylprotein thioesterase activity as well as lysophospholipase activity, but thioacylproteins are by far the preferred substrates. The second acylprotein thioesterase, protein palmitoylthioesterase-1 (L.A. Camp,... 

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. 

Lipoprotein lipase and hepatic lipase are two lipases that degrade triacylglycerols in lipoproteins (Chapter 19) and also demonstrate significant PL A, activity. The enzymes have 50% sequence identity and are members of a superfamily of lipases and phospholipases that share the G-X-S-X-G motif at the active site and an Asp-His-Ser triad that is required for catalysis. Hepatic lipase is about 2-3-fold more efficient at hydrolyzing phospholipids than is lipoprotein lipase and has lysophospholipase activity. Another lipase, intestinal lipase, has lysophospholipase activity and is also referred to as a PLB. 

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. 

Fifth, esterase activity can be due to enzymes with nonesterase main activities. Thus, lysophospholipase (EC 3.1.1.5) and carbonic anhydrase (EC... 

In addition to membrane-bound PLAiS, mammals have cytosolic PLAjS. Cytosolic PLAi activities have been studied in various tissues including heart, brain and testis. PA-PLAi has been purified from brain [45] and testes [39, 46]. Like other lipolytic enzymes, PLAi is affected by the assay conditions. Using a mixed micelle system Glomset and his colleagues [46] found that a 110 kDa enzyme from testes preferentially hydrolyzed phosphatidic acid. They cloned the PA-PLAi from bovine [16]. This PLAi lacks sequence similarity to type I PLAi, lysophospholipase, LCAT, and triacylglycerol lipases. 

Umezu-Goto M, Kishi Y, Taira A, Hama K, Dohmae N, Takio K, Yamori T, Mills GB, Inoue K, Aoki J, Aral H (2002) Autotaxin has lysophospholipase D activity leading to tumor cell growth and mohUty by lysophosphatidic acid production. J Cell Biol 158 227-233... 

Early studies with purified ricin demonstrated calcium-independent phospholipase type A and A2 activity, as well as nonspecific acyl hydrolase lysophospholipase type A and A2 activity... 

Pancreatic carboxylester lipase, secreted by the pancreas as an active enzyme without proteolytic activation, displays broad substrate specificity and has therefore received many names in the literature carboxylesterase, bile salt-stimulated (or activated or dependent) lipase (due to its absolute requirement for bile salts to hydrolyze insoluble substrates), carboxylester lipase or hydrolase, cholesterol esterase, lysophospholipase, nonspecific lipase, and monoglyceride lipase. The IUPAC classification of the enzyme has been either EC.3.1.1.1 (carboxylester hydrolase) or EC.3.1.1.13 (cholesterolester hydrolase) (Table 2). 

I also appears to possess lysophospholipase LI activity. Thioesterase II is a cytosolic tetrameric protein composed of 32-kDa subunits encoded by the tesB gene. Thioesterase... 

Fig. 13. Catabolism of platelet-activating factor (PAF) and its metabolites by (I) PAF-AH, (II) lysophospholipase D, (III) phosphohydrolase, (IV) phospholipase C, (V) Cok-independent or CoA-dependenI transacylase, and/or (VI) alkylacetylglycerol acetylhydrolase. The O-alkyl linkage in products that contain free hydroxyl groups can be cleaved by (VII) the O-alkyl Pte H4-dependent monooxygenase.

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]. 

The catalytic domain The cPLA2 shows lysophospholipase and transacylase activities that are consistent with the formation of an acyl-serine intermediate characteristic of lipases and Ser-228 has been identified as the involved residue. In addition, Asp-549 has been demonstrated to be the second member of the predicted catalytic triad. However, histidine has not been identified as the third member and none of the 19 histidine residues in the protein has been shown to play any catalytic role. At present, a dyad mechanism must be invoked while Arg-200 is in a position to stabilize the oxyanion intermediate. Interestingly, 1-palmitoyl lysophosphatidylcholine is degraded at a rate comparable to that of 2-arachidonoyl phosphatidylcholine, which raises the possibility that the enzyme serves multiple functions in the cell. The other isoenzymes of CPLA2 also have these three conserved active-site residues (R, S, and D). 

Farooqui, A.A., Liss, L. and Horrocks, L.A. (1990) Elevated activities of lipases and lysophospholipases in Alzheimer s disease. Dementia 1 208-214. 

Organophosphate-induced delayed neuropathy is unrelated to the anticholinesterase (anti-ChE) effects of OP agents because many highly potent cholinergic OPs do not cause neuropathy, and other OP compounds such a.s tri-o-cresyl phosphate (which is not used as a pesticide) have only weak anti-ChE activity but are powerful inducers of neuropathy. The enzyme involved in organo-phosphatc-induced delayed neuropathy is neuropathy target esterase—lysophospholipase (Lush et al 1998 ... 

Phospholipase D - Phospholipase D cleaves the phosphoester bond between phosphatidic acid and the alcoholic moiety of different phospholipids. It is widely present in plants but few reports have indicated the presence of phospholipase D in mammalian tissues.1 In rat brain a phospholipase D that converts phosphatidylcholine to phosphatidic acid has been studied.100 Eosinophils also contain a phospholipase D activity.101 A lysophospholipase D activity seems to have an absolute specificity for 1-alkyl-sn-glycero-3-phosphoethanolamine or -choline102 and it is present in microsomes of rat brain,103 kidney, intestine, lung, testes and liver.104 A recent report indicates that a phospholipase D might be activated in human and rabbit neutrophils stimulated with chemotactlc peptides.105 This activity would induce a net loss of phosphatidylinositol with a net gain in phosphatidic acid. However, this activity has not yet been characterized and its function is not known. 

Sugimoto, H. and Yamashita, S. (1999) Characterization of the transacylase activity of rat liver 60-kDa lysophospholipase-transacylase. Acyl transfer from the sn-2 to the sn-1 position. Biochim Biophys Acta. 1438 264-272. 

---