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Biological & Pharmaceutical Bulletin Aug 2004Secretory phospholipase A2 (sPLA2) is a growing family of structurally related, disulfide-rich, low molecular weight, lipolytic enzymes with a His-Asp catalytic dyad....
Secretory phospholipase A2 (sPLA2) is a growing family of structurally related, disulfide-rich, low molecular weight, lipolytic enzymes with a His-Asp catalytic dyad. sPLA2s are distributed in a wide variety of vertebrate and invertebrate animals, plants, bacteria, and viruses, and there are 10 catalytically active sPLA2 isozymes in mammals. Although the structural bases for mammalian sPLA2s have been well documented, their physiological functions are still subject to debate. Individual mammalian sPLA2s have distinct enzymatic properties and display distinct tissue expression patterns, suggesting that each enzyme acts on distinct phospholipid membrane moieties in vivo. In this article, we briefly review our latest understanding of the possible physiological functions of sPLA2s, in keeping with their diverse actions on mammalian and nonmammalian cell membranes.
Topics: Animals; Catalysis; Mammals; Phospholipases A; Phospholipases A2
PubMed: 15305013
DOI: 10.1248/bpb.27.1158 -
Molecular Neurobiology 1989Many neurotransmitters and hormones activate receptors that are known to be coupled to their effectors by GTP-binding regulatory proteins, G proteins. Activation of many... (Review)
Review
Many neurotransmitters and hormones activate receptors that are known to be coupled to their effectors by GTP-binding regulatory proteins, G proteins. Activation of many of these same receptors elicits arachidonate release and metabolism. During the past few years, novel experimental techniques have revealed that in many cells arachidonate release is independent of generation of other second messengers, including inositol phosphates, diacylglycerols, and elevation in free intracellular calcium. Much evidence has accumulated to implicate phospholipase A2 as the enzyme catalyzing arachidonate release, and suggesting that this effector enzyme, too, is activated by G proteins. In neural tissues as well as epithelium, endothelium, contractile and connective tissues, and blood cells, G proteins coupled to receptors for a variety of peptide and nonpeptide neurotransmitters and hormones have been shown to directly activate phospholipase A2. In retinal rod outer segments, transducin is the coupling G protein, but the G proteins coupling receptor activation to phospholipase A2 in other cell types is less clear. Some are pertussis toxin-sensitive, whereas others are not, and evidence exists that the ras gene product G protein may also be coupled to and regulate phospholipase A2.
Topics: Animals; Arachidonic Acid; Arachidonic Acids; GTP-Binding Proteins; Phospholipases; Phospholipases A; Phospholipases A2
PubMed: 2510770
DOI: 10.1007/BF02935629 -
Methods in Molecular Biology (Clifton,... 2004Mammalian cells contain many structurally and functionally diverse phospholipases A2 (PLA2) that catalyze the hydrolysis of sn-2 fatty acid from membrane phospholipid....
Mammalian cells contain many structurally and functionally diverse phospholipases A2 (PLA2) that catalyze the hydrolysis of sn-2 fatty acid from membrane phospholipid. Assays are described for measuring the activity of Group IVA cytosolic PLA2alpha(cPLAalpha) and for secreted PLA2s (sPLA2) that are suitable for purified enzymes and for measuring activity in crude cell lysates and culture medium. The assay for cPLA2alpha involves measuring the calcium-dependent release of radiolabeled sn-2 arachidonic acid from small unilamellar vesicles of phosphatidylcholine. Methods are described for distinguishing cPLA2alpha activity in cell lysates from other PLA2s. sPLA2 activity is monitored using a fluorimetric assay that measures the continuous calcium-dependent formation of albumin-bound pyrene fatty acid from the sn-2 position of phosphatidylglycerol.
Topics: Animals; Cell Extracts; Fatty Acids; Fluorometry; Group II Phospholipases A2; Group IV Phospholipases A2; Group VI Phospholipases A2; Humans; Isotope Labeling; Phospholipases A; Phospholipases A2; Substrate Specificity
PubMed: 15173620
DOI: 10.1385/1-59259-816-1:229 -
Trends in Biochemical Sciences Jan 1997
Review
Topics: 1-Alkyl-2-acetylglycerophosphocholine Esterase; Animals; Calcium; Humans; Multigene Family; Phospholipases A; Phospholipases A2; Signal Transduction
PubMed: 9020581
DOI: 10.1016/s0968-0004(96)20031-3 -
Plant Physiology May 2020
Topics: Phosphatidic Acids; Phospholipase D; Phospholipases; Plant Immunity
PubMed: 32385184
DOI: 10.1104/pp.20.00352 -
Progress in Nucleic Acid Research and... 2001The group VIA PLA2 is a member of the PLA2 superfamily. This enzyme, which is cytosolic and Ca2+-independent, has been designated iPLA2beta to distinguish it from... (Review)
Review
The group VIA PLA2 is a member of the PLA2 superfamily. This enzyme, which is cytosolic and Ca2+-independent, has been designated iPLA2beta to distinguish it from another recently cloned Ca2+-independent PLA2. Features of iPLA2beta molecular structure offer some insight into possible cellular functions of the enzyme. At least two catalytically active iPLA2beta isoforms and additionalsplicing variants are derived from a single gene that consists of at least 17 exons located on human chromosome 22q13.1. Potential tumor suppressor genes also reside at or near this locus. Structural analyses reveal that iPLA2beta contains unique structural features that include a serine lipase consensus motif (GXSXG), a putative ATP-binding domain, an ankyrin-repeat domain, a caspase-3 cleavage motif DVTD138Y/N, a bipartite nuclear localization signal sequence, and a proline-rich region in the human long isoform. iPLA2beta is widely expressed among mammalian tissues, with highest expression in testis and brain. iPLA2beta prefers to hydrolyze fatty acid at the sn-2 fatty acid substituent but also exhibits phospholipase A1, lysophospholipase, PAF acetylhydrolase, and transacylase activities. iPLA2beta may participate in signaling, apoptosis, membrane phospholipid remodeling, membrane homeostasis, arachidonate release, and exocytotic membrane fusion. Structural features and the existence of multiple splicing variants of iPLA2beta suggest that iPLA2beta may be subject to complex regulatory mechanisms that differ among cell types. Further study of its regulation and interaction with other proteins may yield insight into how its structural features are related to its function.
Topics: Alternative Splicing; Amino Acid Sequence; Calcium; Chromosome Mapping; Humans; Molecular Sequence Data; Phospholipases A; Phospholipases A1; Phospholipases A2; Sequence Homology, Amino Acid; Terminology as Topic
PubMed: 11525380
DOI: 10.1016/s0079-6603(01)67023-5 -
Reviews of Physiology, Biochemistry and... 1981
Review
Topics: Animals; Catalysis; Chemical Phenomena; Chemistry; Humans; Kinetics; Phospholipases; Phospholipases A; Phospholipases A2; Protein Binding; X-Ray Diffraction
PubMed: 7031820
DOI: 10.1007/3-540-10961-7_3 -
Environmental Health Perspectives Mar 1990Calcium has been implicated as a regulatory factor in many physiological and pathophysiological processes in the renal cell. Under physiological conditions, the... (Review)
Review
Calcium has been implicated as a regulatory factor in many physiological and pathophysiological processes in the renal cell. Under physiological conditions, the cytosolic free calcium concentration is maintained at approximately 100 nM. Most of the releasable cell Ca2+ resides in the nonmitochondrial compartments. In addition to the plasma membrane Ca2+ transport processes, there is a high-affinity, low-capacity buffering capability of nonmitochondrial organelles and a lower-affinity high-capacity mitochondrial Ca2+ buffering capability. A critical enzymatic effector of Ca2+ action in the cell is phospholipase A2. By using digitonin-permeabilized renal mesangial cells, the [Ca2+] dependency of phospholipase A2 was characterized. The [Ca2+] sensitivity was insufficient to explain the phospholipase A2 activation observed with vasopressin. In both intact cells, as well as permeabilized cells, it was found that protein kinase C activation markedly enhanced the Ca2+ calmodulin-dependent activation of phospholipase A2. In response to platelet-derived growth factor, it was found that arachidonic acid release preceded phospholipase C activation. This suggests that other effectors besides Ca2+ and protein kinase C may also be important for phospholipase A2 activation. In an experimental model designed to mimic postischemic reperfusion damage to renal mitochondria, it was demonstrated that reactive oxygen species act synergistically with Ca2+ to activate mitochondrial phospholipase A2, which mediates damage to site I of the electron transport chain, the F1F0 ATPase, and the adenine nucleotide translocase.(ABSTRACT TRUNCATED AT 250 WORDS)
Topics: Animals; Calcium; Enzyme Activation; Humans; Kidney; Phospholipases; Phospholipases A; Phospholipases A2
PubMed: 2190810
DOI: 10.1289/ehp.9084155 -
Infection and Immunity Aug 1991Three types of phospholipase activity--phospholipase A1, A2, and lysophospholipase--were detected in Mycobacterium leprae harvested from armadillo tissue at about 25% of...
Three types of phospholipase activity--phospholipase A1, A2, and lysophospholipase--were detected in Mycobacterium leprae harvested from armadillo tissue at about 25% of the specific activity found in a slowly growing mycobacterium, Mycobacterium microti, which was grown in medium to optimize its phospholipase activity. The highest activity found was lysophospholipase, which released fatty acid from 2-lyso-phosphatidylcholine. Phospholipase activity was detected by using phosphatidylcholine and phosphatidylethanolamine. Differences in relative activities with these three types of substrate distinguished phospholipase activity in M. leprae extracts from armadillo liver extracts. Furthermore, retention of activity in M. leprae after NaOH treatment showed that the activity associated with M. leprae was not host derived. The specific activity of phospholipase was 20 times higher in extracts of M. leprae than in intact M. leprae organisms. Diazotization, a treatment which abolishes activities of surface enzymes exposed to the environment by the formation of covalent azide bonds with exposed amino groups, did not affect M. leprae's phospholipase activity, with one exception: release of arachidonic acid from phosphatidylcholine, which was partially inhibited. Phenolic glycolipid I, the major excreted amphipathic lipid of M. leprae, inhibited phospholipase activity, including release of arachidonic acid, for both M. leprae- and armadillo-derived activity.
Topics: Animals; Antigens, Bacterial; Armadillos; Glycolipids; Hydrolysis; Lysophospholipase; Mycobacterium leprae; Phospholipases; Phospholipases A; Phospholipases A1; Phospholipids; Substrate Specificity
PubMed: 1855994
DOI: 10.1128/iai.59.8.2781-2789.1991 -
Current Topics in Medicinal Chemistry 2007The enzyme phospholipase A2 catalyzes the cleavage of the sn-2 acyl ester bond of phospholipids, leading to the production of free fatty acids and lysophospholipids,... (Review)
Review
The enzyme phospholipase A2 catalyzes the cleavage of the sn-2 acyl ester bond of phospholipids, leading to the production of free fatty acids and lysophospholipids, which leads to many inflammatory disorders. In view of its pharmaceutical interest, three phospholipase A2 + inhibitor (namely, (i) L-1-O-octyl-2-heptylphosphonyl-sn-glycero-3-phosphoethanolamine, Transition State Analogue, (ii) 1-Hexadecyl-3-(trifluoroethyl)-sn-glycero-2-phosphomethanol, MJ33 and (iii) p-methoxybenzoic acid, anisic acid) complex structures have already been solved and analysed, using the data obtained from X-ray diffraction. These structures provide insight on the mode of binding of the inhibitor molecules at the active site of phospholipase A2. The knowledge of the active site geometry in these inhibitor bound structures, yield valuable information in the design of more useful therapeutic agents. This report reviews only the inhibitor bound recombinant bovine pancreatic phospholipase A2 structures solved using X-ray crystallography.
Topics: Animals; Binding Sites; Cattle; Crystallography, X-Ray; Models, Molecular; Mutation; Pancreas; Phospholipases A; Phospholipases A2; Recombinant Proteins
PubMed: 17456041
DOI: 10.2174/156802607780487632