Eicosanoids families

LEUKOTRIENE RECEPTOR AGONISTS act at receptors recognizing leukotrienes and analogues. The lipoxygenase system forms the leukotrienes, which are members of the eicosanoid family of phospholipid mediators. Their name derives from the fact that leukotrienes are found in leucocytes and contain a triene system of double bonds. The other members of the eicosanoid family are the prostanoids (thromboxanes and the prostaglandins), and these are formed by the cyclooxygenase system see cyclooxygenase INHIBITORS. All the eicosanoids are derived mainly from arachidonic acid. These mediators are synthesized on demand, and in some cases their half-lives are short. The... 

Reports that AA is released primarily by G-protein-mediated PLA2 activation remain to be confirmed [84, 85]. In addition, modulation of PLA2 by Ca2+ and protein kinase needs to be better defined. It is clear that NMDA receptor activation promotes the release of AA [86], and that a variety of eicosanoids are then generated (Fig 33-2,33-3). The modulatory events that channel AA towards specific eicosanoids are not understood. The endocannabinoid family of lipid messengers will remain an active focus of interest because of the growing evidence of their actions in synaptic function, learning, memory, and other forms of behavior [56,87]. 

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... 

Before taking leave of the eicosanoids, 1 need to point out that a second enzyme, 5-lipoxygenase, also metabolizes arachidonic acid. 5-Lipoxygenase initiates the synthesis of the leukotrienes from arachidonic acid. There is a whole family of leukotrienes and these molecules have a spectrum of biological properties. 1 will focus on one important leukotriene, LTB4. 

The autacoids comprise histamine, serotonin, angiotensin, neurotensin, NO (nitric oxide), kinins, platelet-activating factor, endothelins and the four families of traditional eicosanoids - the leukotrienes and three types of prostanoids i.e. prostaglandins, prostacyclins, and thromboxanes. Several other natural occurring molecules are sometimes called eicos-anoid, including the hepoxilins, resolvins, isofurans, isoprostanes, lipoxins, epoxyeicosatrienoic acids (EETs) and some endocannabinoids. However, not... 

Mammals cannot make linoleate and must obtain it from plant sources they convert exogenous linoleate to arachidonate, the parent compound of eicosanoids (prostaglandins, thromboxanes, and leukotrienes), a family of very potent signaling molecules. 

Prostaglandin A member of the family of 20-carbon fatty acid compounds (eicosanoids) formed from arachidonic acid by the cyclooxygenase enzyme. Prostaglandins help regulate normal cell activity, and may help mediate certain pathologic responses, including pain, inflammation, fever, and abnormal blood coagulation. 

Prenylated flavonoids contain one or two isoprenyl, geranyl, dimethylallyl, and lavandulyl on the skeleton. They have limited distribution and are mostly isolated from the Moraceae family. Chi et al. isolated 19 prenylated flavonoids from six different genera of Chinese medicinal plants and evaluated inhibition activities on eicosanoid metabolisms with multiple cell line models [189]. Two 8-lavandulylated flavanones, kurarinone and sophoraflavanone G, were discovered to be dual inhibitors. They possessed the most potent COX-1 inhibitory activities with IC50 less than 1 pM comparable with that of indomethacin. Sophoraflavanone G isolated from the roots of Sophora flavescense Art (Fabaceae) also had potent 5-LOX inhibition activity with an IC50 below 0.25 pM. 

Each of the other families of eicosanoids—thromboxanes and leukotrienes—has interesting biosynthetic pathways too, but we will mention only one small detail. A completely different oxidation enzyme, lipoxygenase, initiates a separate pathway leading to the leukotrienes, but the first steps are very similar. They just occur elsewhere in the arachidonic acid molecule. 

The FABPs are a family of carrier proteins for fatty acids and other lipophilic substances, such as eicosanoids and retinoids. These proteins are thought to facilitate the transfer of fatty acids between extra- and intracellular membranes. Adipocyte fatty acid-binding protein (aP2 FABP4) is expressed in adipocytes and macrophages, and integrates inflammatory and metabolic responses. Studies in aP2-deflcient mice have shown that this lipid chaperone has a significant role in several aspects of the metabolic syndrome, including type 2 diabetes and atherosclerosis. FABP has also been introduced as a plasma marker of acute myocardial infarction. 

Other interesting examples of positional isomer separation involving NPC are (a) the separation of dihydrodipyridopyridopyrazines, a new family of antitumor agents, on a silica Nucleosil 50 A-lOpm column [43] and (b) the separation of celecoxib isomers by Chiralpak AD column [44], NPC was also employed successfully for the resolution of (a) four configurational isomers of a steroidal calyx pyrrole [45], (b) regio- and stereoisomers of eicosanoids [46], (c) retinal and retinol isomers [47], and (d) several ElZ isomers pairs of vitamin A [48],... 

Wendelborn DF, Seibert K, Roberts LJ Jr. Isomeric prostaglandin F2 compounds arising from prostaglandin D2 a family of eicosanoids produced in vivo in humans. Proc. Natl. Acad. Sci. U.S.A. 1988 85 304. 

Dietary fat serves several important nutritional functions. It is the source of essential fatty acids. Members of the n-6 and n-3 (also known as the co-6 and co-3) families of fatty acids are important constituents of cell membranes and serve as precursors of eicosanoids (biologically active compounds such as prostaglandins, thromboxanes, prostacyclins, and leukotrienes). Fat also serves as a carrier for the fat-soluble vitamins, and it is important source of energy. In addition, it has important culinary properties and contributes to the palatability of food. 

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