Prostaglandins and other

Mammals can add additional double bonds to unsaturated fatty acids in their diets. Their ability to make arachidonic acid from linoleic acid is one example (Figure 25.15). This fatty acid is the precursor for prostaglandins and other biologically active derivatives such as leukotrienes. Synthesis involves formation of a linoleoyl ester of CoA from dietary linoleic acid, followed by introduction of a double bond at the 6-position. The triply unsaturated product is then elongated (by malonyl-CoA with a decarboxylation step) to yield a 20-carbon fatty acid with double bonds at the 8-, 11-, and 14-positions. A second desaturation reaction at the 5-position followed by an acyl-CoA synthetase reaction (Chapter 24) liberates the product, a 20-carbon fatty acid with double bonds at the 5-, 8-, IT, and ITpositions. 

Schlondorff, D. and Ardaillon, R. (1986). Prostaglandins and other arachidonic acid metabolites in the kidney. Kidney Int. 29, 108-119. 

The stimulus for the recent surge of activity in this previously dormant area of organic chemistry can be traced to the prostaglandin connection . That is to the discovery that saturated bicyclic peroxides are key intermediates in the biosynthesis of prostaglandins and other physiologically active substances by the enzymatic oxygenation of polyunsaturated fatty acids. 

Fig. 6.11. Formation and function of diacylglycerol. The figure schematically shows two main pathways for formation of diacylglycerol (DAG). DAG can be formed from PtdInsP2 by the action of phospholipase C (PL-C). Another pathway starts from phosphatidyl chohne. Phospholipase D (PL-D) converts phosphatidyl choline to phosphatidic add (Ptd), and the action of phosphatases results in DAG. Arachidonic add, the starting point of biosynthesis of prostaglandins and other intracellular and extracellular messenger substances, can be cleaved from DAG. PKC protein kinase C Ptdins phosphatidyl inositol.

Wang D, Mann JR, DuBois RN The role of prostaglandins and other eicosanoids in the gastrointestinal tract. Gastroenterology 2005 128 1445. [PMID 15887126]... 

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). 

The biosynthetic pathway of prostaglandins and other eicosanoids is outlined in Figure 15-2. Basically, these compounds are derived from a 20-carbon essential fatty acid. In humans, this fatty acid is usually arachi-donic acid,68,73 which is ingested in the diet and stored as a phospholipid in the cell membrane. Thus, the cell has an abundant and easily accessible supply of this... 

The most important known effects of the prostaglandins and other eicosanoids are the contraction and relaxation of smooth muscles ... 

Subsequent exposure to antigen results in binding to surface-bound IgE molecules. The sensitized mast cells are stimulated to release granules containing histamine, leukotrienes, prostaglandins, and other potent chemical mediators. 

Figure 9.5. CYP epoxygenase- and hydroxylase-mediated metabolism of arachidonic acid. Products include biologically active EETs and HETEs. (Adapted from Seubert et al. Prostaglandins and Other Lipid Mediators 82, 50-59, 2007.)...

The early stages in the biosynthesis of prostaglandins and other eicosanoids in mammals are outlined in Scheme 6. From what is known at this stage, the pathway is very similar in invertebrates.130... 

Figure 7-1 Sensitization of nociceptors by prostaglandins and other inflammatory mediators to produce pain and inflammation in ocular tissues. Clinically useful analgesics act either in peripheral tissues by inhibiting prostaglandin production or centrally by interrupting the pain signal and its emotional consequences. (CNS = central nervous system NSAlDs = nonsteroidal anti-inflammatory drugs PGE2 = prostaglandin E2.)...

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