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30-639: This particular phospholipase specifically recognizes the sn 2 acyl bond of phospholipids and catalytically hydrolyzes the bond, releasing arachidonic acid and lysophosphatidyl choline , a precursor of lysophosphatidic acid . Upon downstream modification by cyclooxygenases or lipoxygenases , arachidonic acid is modified into active compounds called eicosanoids . Eicosanoids include prostaglandins and leukotrienes , which are categorized as anti-inflammatory and inflammatory mediators. PLA 2 enzymes are commonly found in mammalian tissues as well as arachnid, insect, and snake venom. Venom from bees

60-499: A 1% risk of fetal aneuploidy . The risk of aneuploidy increases to 10.5-12% if other risk factors or ultrasound findings are noted. Size, location, disappearance or progression, and whether the cysts are found on both sides or not do not affect the risk of aneuploidy. 44-50% of Edwards syndrome (trisomy 18) cases will present with choroid plexus cysts, as well 1.4% of Down syndrome (trisomy 21) cases. ~75% of abnormal karyotypes associated with choroid plexus cysts are trisomy 18, while

90-579: A different 3D structure and are significantly larger than secreted PLA 2 (more than 700 residues). They include a C2 domain and a large catalytic domain. These phospholipases are involved in cell signaling processes, such as inflammatory response . They release arachidonic acid from membrane phospholipids. Arachidonic acid is both a signaling molecule and the precursor for the synthesis of other signaling molecules termed eicosanoids . These include leukotrienes and prostaglandins . Some eicosanoids are synthesized from diacylglycerol , released from

120-571: A pharmaceutical approach to treatment of several disorders associated with neural trauma. Increase in phospholipase A 2 activity is an acute-phase reaction that rises during inflammation, which is also seen to be exponentially higher in low back disc herniations compared to rheumatoid arthritis . It is a mixture of inflammation and substance P that are responsible for pain. Increased phospholipase A 2 has also been associated with neuropsychiatric disorders such as schizophrenia and pervasive developmental disorders (such as autism ), though

150-414: Is a plexus of cells that arises from the tela choroidea in each of the ventricles of the brain . Regions of the choroid plexus produce and secrete most of the cerebrospinal fluid (CSF) of the central nervous system . The choroid plexus consists of modified ependymal cells surrounding a core of capillaries and loose connective tissue . Multiple cilia on the ependymal cells move to circulate

180-603: Is analogous to neurological diseases such as Alzheimer's disease , epilepsy , multiple sclerosis , ischemia . Lysophospholipids are another class of molecules released from the membrane that are upstream predecessors of platelet activating factors (PAF). Abnormal levels of potent PAF are also associated with neurological damage. An optimal enzyme inhibitor would specifically target PLA 2 activity on neural cell membranes already under oxidative stress and potent inflammation . Thus, specific inhibitors of brain PLA 2 could be

210-476: Is characterized as the degradation of the tetrahedral intermediate composed of a calcium coordinated oxyanion . The role of calcium can also be duplicated by other relatively small cations like cobalt and nickel. Before becoming active in digestion, the proform of PLA 2 is activated by trypsin. PLA 2 can also be characterized as having a channel featuring a hydrophobic wall in which hydrophobic amino acid residues such as Phe , Leu , and Tyr serve to bind

240-1153: Is largely composed of melittin , which is a stimulant of PLA 2 . Due to the increased presence and activity of PLA 2 resulting from a snake or insect bite, arachidonic acid is released from the phospholipid membrane disproportionately. As a result, inflammation and pain occur at the site. There are also prokaryotic A 2 phospholipases . Additional types of phospholipases include phospholipase A 1 , phospholipase B , phospholipase C , and phospholipase D . Phospholipases A 2 include several unrelated protein families with common enzymatic activity. Two most notable families are secreted and cytosolic phospholipases A 2 . Other families include Ca independent PLA 2 (iPLA 2 ) and lipoprotein-associated PLA 2 (Lp-PLA 2 ), also known as platelet activating factor acetylhydrolase (PAF-AH). The extracellular forms of phospholipases A 2 have been isolated from different venoms ( snake , bee , and wasp ), and from virtually every studied mammalian tissue (including pancreas and kidney ) as well as from bacteria . They require Ca for activity. Pancreatic sPLA 2 serve for

270-759: Is observed in the cerebrospinal fluid of humans with Alzheimer's disease and multiple sclerosis , and may serve as a marker of increases in permeability of the blood-cerebrospinal fluid barrier . There are atypical members of the phospholipase A 2 family, such as PLA2G12B , that have no phospholipase activity with typical phospholipase substrate. The lack of enzymatic activity of PLA2G12B indicates that it may have unique function distinctive from other sPLA 2 . It has been shown that in PLA2G12B null mice, VLDL levels were greatly reduced, suggesting it could have an effect in lipoprotein secretion. The intracellular , group IV PLA 2 are also Ca-dependent, but they have

300-416: Is phosphorylated by a MAPK at Serine -505. When phosphorylation is coupled with an influx of calcium ions, cPLA 2 becomes stimulated and can translocate to the membrane to begin catalysis . Phosphorylation of cPLA 2 may be a result of ligand binding to receptors, including: In the case of an inflammation, the application of glucocorticoids up-regulate (mediated at the gene level) the production of

330-498: Is primarily a phospholipase. Phospholipase A 2 acts on the intact lecithin molecule and hydrolyzes the fatty acid esterified to the second carbon atom. The resulting products are lysolecithin and a fatty acid. Phospholipase A 2 is an enzyme present in the venom of bees , blennies and viper snakes . This enzyme -related article is a stub . You can help Misplaced Pages by expanding it . Blood-cerebrospinal fluid barrier The choroid plexus , or plica choroidea ,

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360-424: The lipid bilayer by phospholipase C (see below). Phospholipases A 2 can be classified based on sequence homology. Increased levels of Lp-PLA 2 are associated with cardiac disease, and may contribute to atherosclerosis . However, the role of Lp-PLA 2 in atherosclerosis may depend on its carrier in plasma, and several lines of evidence suggest that HDL-associated Lp-PLA 2 may substantially contribute to

390-511: The HDL antiatherogenic activities. The suggested catalytic mechanism of pancreatic sPLA 2 is initiated by a His-48/Asp-99/calcium complex within the active site. The calcium ion polarizes the sn-2 carbonyl oxygen while also coordinating with a catalytic water molecule, w5. His-48 improves the nucleophilicity of the catalytic water via a bridging second water molecule, w6. It has been suggested that two water molecules are necessary to traverse

420-408: The brain. The blood–cerebrospinal fluid barrier (BCSFB) is a fluid–brain barrier that is composed of a pair of membranes that separate blood from CSF at the capillary level and CSF from brain tissue. The blood–CSF boundary at the choroid plexus is a membrane composed of epithelial cells and tight junctions that link them. There is a CSF-brain barrier at the level of the pia mater, but only in

450-581: The brain. This cellular trafficking has implications both in normal brain homeostasis and in neuroinflammatory processes . During fetal development , some choroid plexus cysts may form. These fluid-filled cysts can be detected by a detailed second trimester ultrasound . The finding is relatively common, with a prevalence of ~1%. Choroid plexus cysts are usually an isolated finding. The cysts typically disappear later during pregnancy, and are usually harmless. They have no effect on infant and early childhood development. Choroid plexus cysts are associated with

480-414: The cerebrospinal fluid. There is a choroid plexus in each of the four ventricles . In the lateral ventricles , it is found in the body , and continued in an enlarged amount in the atrium . There is no choroid plexus in the anterior horn . In the third ventricle , there is a small amount in the roof that is continuous with that in the body, via the interventricular foramina , the channels that connect

510-405: The distance between the catalytic histidine and the ester . The basicity of His-48 is thought to be enhanced through hydrogen bonding with Asp-99. An asparagine substitution for His-48 maintains wild-type activity, as the amide functional group on asparagine can also function to lower the p K a , or acid dissociation constant , of the bridging water molecule. The rate limiting state

540-466: The embryo. Similar to the blood–brain barrier , the blood–CSF barrier functions to prevent the passage of most blood-borne substances into the brain, while selectively permitting the passage of specific substances (such as nutrients) into the brain and facilitating the removal of brain metabolites and metabolic products into the blood. Despite the similar function between the BBB and BCSFB, each facilitates

570-428: The ependyma, the choroid plexus epithelial layer has tight junctions between the cells on the side facing the ventricle (apical surface). These tight junctions prevent the majority of substances from crossing the cell layer into the cerebrospinal fluid (CSF); thus the choroid plexus acts as a blood–CSF barrier. The choroid plexus folds into many villi around each capillary, creating frond-like processes that project into

600-679: The formation of fatty acids including arachidonic acid . This arachidonic acid is then metabolized to form several inflammatory and thrombogenic molecules. Excess levels of sPLA 2 is thought to contribute to several inflammatory diseases , and has been shown to promote vascular inflammation correlating with coronary events in coronary artery disease and acute coronary syndrome , and possibly leading to acute respiratory distress syndrome and progression of tonsillitis . In children, excess levels of sPLA 2 have been associated with inflammation thought to exacerbate asthma and ocular surface inflammation ( dry eye ). Increased sPLA 2 activity

630-442: The initial digestion of phospholipid compounds in dietary fat . Venom phospholipases help to immobilize prey by promoting cell lysis . In mice, group III sPLA 2 are involved in sperm maturation, and group X are thought to be involved in sperm capacitation . sPLA 2 has been shown to promote inflammation in mammals by catalyzing the first step of the arachidonic acid pathway by breaking down phospholipids , resulting in

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660-510: The lateral ventricles with the third ventricle. A choroid plexus is in part of the roof of the fourth ventricle . The choroid plexus consists of a layer of cuboidal epithelial cells surrounding a core of capillaries and loose connective tissue . The epithelium of the choroid plexus is continuous with the ependymal cell layer (ventricular layer) that lines the ventricular system. Progenitor ependymal cells are monociliated but they differentiate into multiciliated ependymal cells. Unlike

690-515: The mechanisms involved are not known. Human phospholipase A 2 isozymes include: In addition, the following human proteins contain the phospholipase A 2 domain : Phospholipase A phospholipase is an enzyme that hydrolyzes phospholipids into fatty acids and other lipophilic substances. There are four major classes, termed A, B, C, and D, which are distinguished by the type of reaction which they catalyze: Types C and D are considered phosphodiesterases . Endothelial lipase

720-462: The protein lipocortin which may inhibit cPLA 2 and reduce the inflammatory response. In normal brain cells, PLA 2 regulation accounts for a balance between arachidonic acid 's conversion into proinflammatory mediators and its reincorporation into the membrane. In the absence of strict regulation of PLA 2 activity, a disproportionate amount of proinflammatory mediators are produced. The resulting induced oxidative stress and neuroinflammation

750-530: The remainder are trisomy 21. There are three graded types of choroid plexus tumor that mainly affect young children. These types of cancer are rare. Choroid plexus translates from the Latin plexus chorioides , which mirrors Ancient Greek χοριοειδές πλέγμα . The word chorion was used by Galen to refer to the outer membrane enclosing the fetus. Both meanings of the word plexus are given as pleating, or braiding. As often happens language changes and

780-406: The removal of metabolic waste from the brain, and the exchange of biomolecules and xenobiotics into and out of the brain. In this way the choroid plexus has a very important role in helping to maintain the delicate extracellular environment required by the brain to function optimally. The choroid plexus is also a major source of transferrin secretion that plays a part in iron homeostasis in

810-454: The substrate. Another component of PLA 2 is the seven disulfide bridges that are influential in regulation and stable protein folding. PLA 2 action can release histamine from rat peritoneal mast cells. It also causes histamine release in human basophils. Due to the importance of PLA 2 in inflammatory responses , regulation of the enzyme is essential. cPLA 2 is regulated by phosphorylation and calcium concentrations. cPLA 2

840-532: The transport of different substances into the brain due to the distinctive structural characteristics of each of the two barrier systems. For a number of substances, the BCSFB is the primary site of entry into brain tissue. The blood–cerebrospinal fluid barrier has also been shown to modulate the entry of leukocytes from the blood to the central nervous system. The choroid plexus cells secrete cytokines that recruit monocyte-derived macrophages , among other cells, to

870-487: The ventricles by choroid epithelial cells. Fluid filters through these cells from blood to become cerebrospinal fluid. There is also much active transport of substances into, and out of, the CSF as it is made. The choroid plexus regulates the production and composition of cerebrospinal fluid (CSF), that provides the protective buoyancy for the brain. CSF acts as a medium for the glymphatic filtration system that facilitates

900-406: The ventricles. The villi, along with a brush border of microvilli, greatly increase the surface area of the choroid plexus. CSF is formed as plasma is filtered from the blood through the epithelial cells. Choroid plexus epithelial cells actively transport sodium ions into the ventricles and water follows the resulting osmotic gradient. The choroid plexus consists of many capillaries, separated from

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