Prostaglandins from arachidonic acid

Eicosanoid (Section 27.4) A lipid derived biologically from 5,8.11,14-eicosatetraenoic acid, or arachidonic acid. Prostaglandins, thromboxanes and leukotrienes are examples. 

Contrary to other elicitors of non-immune anaphylactic reactions (radiocontrast media, neuromuscular blocking agents, non-steroidal anti-inflammatory drugs (NSAIDs)) where there are at least hypothetical concepts regarding the pathomecha-nism of these reactions via increased mediator release (e.g. histamine release, shift in arachidonic acid metabolism from prostaglandins towards leukotrienes, etc.) [26], there is almost no literature regarding the pathomechanism of these reactions after LA application. 

Free radicals are by-products of prostaglandin metabolism and may even regulate the activity of the arachidonate pathway. Arachidonic acid, released from lipids as a result of activation of phospholipases by tissue injury or by hormones, may be metabolized by the prostaglandin or leu-kotriene pathways. The peroxidase-catalysed conversion of prostaglandin G2 to prostaglandin H2 (unstable prostanoids) and the mechanism of hydroperoxy fatty acid to the hydroxy fatty acid conversion both yield oxygen radicals, which can be detected by e.s.r. (Rice-Evans et al., 1991). 

Scheme 6. Proposed biosynthesis of preelavulone A (30) and prostaglandin A2 (41) from arachidonic acid, modified from Corey and coworkers [57]...

Prostaglandins are a subgroup of a larger family of compounds known collectively as eicosanoids, which are synthesized from arachidonic acid (arachidonate) this is a 20-carbon omega-6 unsaturated fatty acid (C20 4). The source of the arachidonic acid for PG synthesis is the cell membrane. Most membrane phospholipids have an unsaturated fatty acid as arachidonate at carbon 2 on the glycerol backbone to help maintain membrane fluidity. The arachidonic acid released from the membrane by the... 

In susceptibie individuais, NSAIDs may precipitate acute bronchospasm. It affects 10-20% of adults with asthma but is rare in asthmatic children. The mechanism is related to cyclooxygenase inhibition, with shunting of arachidonic acid metabolism from the prostaglandin pathway to the biosynthesis of ieukotrienes with increased mucosal permeability and bronchospasm. Susceptible patients should avoid NSAIDs since the bronchospasm may be severe and has been fatal. Paracetamol in doses up to 1000 mg daiiy wiii be toierated by most patients. True type I allergic reactions to NSAIDs, with specific IgE, are rare but anaphyloactoid reactions have occasionally been described in patients with a history of aiiergy or bronchiai asthma. 

Cyclooxygenase (COX), one of the two activities of prostaglandin endoperoxide synthase (PGHS), is the key enzyme in the conversion of arachidonic acid derived from lipids of the cell membrane to prostaglandins and other eicosanoids (Fig. 3). 

Prostaglandins, thromboxanes and leucotrienes are eicosanoids deriving from oxidation of arachidonic acid. Arachidonic acid (deriving from PLA2 action on phospholipids) is cyclized by constitutive cyclooxygenase (COX-1) or inducible cyclooxygenase (COX-2) to yield... 

Calcitriol modulates the maturation of chondrocytes via a cell surface receptor linked to phospholipase and protein kinase C in response to calcitriol, there are rapid changes in arachidonic acid release from, and reincorporation into, membrane phospholipids, and increased synthesis of prostaglandins Ei and E2 (Boyan et al., 1999). 24-Hydroxycalcidiol also modulates the maturation of chondrocytes, acting via cell surface receptors linked to phospholipase D, causing inactivation of both protein kinase C and MAP kinases, thus... 

Arachidonic acid can also be metabolized to a variety of mediators, depending on the cell type. For example, lipoxygenase catalyzes the production of leu-kotrienes, and mixed-function oxygenases catalyze the production of epoxyeicosatrienoic acids. Collectively, these oxygenated metabolites may play a critical role in NSAIEt-induced nephrotic syndrome by shunting arachidonic acid metabolism from prostaglandins to... 

NSAIDs exert their effects by inhibition of the enzyme cyclo-oxygenase (COX). This results in reduced production of prostaglandins and thromboxanes because COX normally catalyses their formation from arachidonic acid. Prostaglandins play a role in pain by sensitising sensory nerve endings to the effects of other mediators such as bradykinin. 

Glutamate-mediated calcium influx results in stimulation arachidonic acid release from neural membrane glycerophospholipids. This release is catalyzed by CPLA2 and PLC/DAG-lipase pathway (McIntosh et al., 1998 Schuhmann et al., 2003 Shohami et al., 1987, 1989 Wei et al., 1982 Dhillon et al., 1996 Homayoun et al., 1997, 2000). Arachidonic acid release occurs in traumatic as well as fluid percussion models of brain injury (FPI). Enzymic oxidation of arachidonic acid generates prostaglandins, leukotrienes, and thromoboxanes whereas non-enzymic oxidation produces isoprostanes and ROS which include superoxide and hydroxyl radicals (Farooqui and Horrocks, 2007). 

Bergstrom, S., Danielsson, H. and Samuelsson, B. (1964). The enzymatic formation of prostaglandin E2 from arachidonic acid. Prostaglandins and related factors 32. Biochim. Biophys. Acta, 90, 207-210... 

Manku, M. S., Oka, M., and Horrobin, D. F., 1979, Differential regulation of the formation of prostaglandins and related substances from arachidonic acid and from dihomogammalinolenic acid. II. Effects of vitamin C, Prostaglandins Med. 3 129-137. 

Prostaglandins are a group of C20 lipids found in all human tissues and fluids. They are derived biosynthetically from all-cis eicosa-5,8,11,14-tetraenoic acid, known commonly as arachidonic acid. Prostaglandin El is an example. Draw arachidonic acid in such a way that it is structurally similar to PGEi in geometry, and identify the two carbons that must form a bond. 

Cyclooxygenase type 2 (COX2) is an important mediator of inflammation involved in prostaglandin synthesis (Fig. 17.3). Arachidonic acid, released from... 

Prostaglandins arise from unsaturated C20 carboxylic acids such as arachidonic acid (see Table 26 1) Mammals cannot biosynthesize arachidonic acid directly They obtain Imoleic acid (Table 26 1) from vegetable oils m their diet and extend the car bon chain of Imoleic acid from 18 to 20 carbons while introducing two more double bonds Lmoleic acid is said to be an essential fatty acid, forming part of the dietary requirement of mammals Animals fed on diets that are deficient m Imoleic acid grow poorly and suffer a number of other disorders some of which are reversed on feed mg them vegetable oils rich m Imoleic acid and other polyunsaturated fatty acids One function of these substances is to provide the raw materials for prostaglandin biosynthesis... 

Studies of the biosynthesis of PGE2 from arachidonic acid have shown that all three oxygens come from O2 The enzyme involved prostaglandin endoperoxide syn tliase has cyclooxygenase (COX) activity and catalyzes the reaction of arachidonic acids with O2 to give an endoperoxide (PGG2)... 

Transport in the blood is no longer a requisite for a hormonal response. Responses can occur after release of hormones into the interstitial fluid with binding to receptors in nearby ceUs, called paracrine control, or binding to receptors on the ceU that released the hormone, called autocrine control. A class of hormones shown to be synthesized by the tissue in which they act or to act in the local ceUular environment are the prostaglandins (qv). These ubiquitous compounds are derived from arachidonic acid [506-32-1] which is stored in the ceU membranes as part of phosphoHpids. Prostaglandins bind to specific ceUular receptors and act as important modulators of ceU activity in many tissues. 

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