Arachidonic acid thromboxane synthesis involved

Animal cells can modify arachidonic acid and other polyunsaturated fatty acids, in processes often involving cyclization and oxygenation, to produce so-called local hormones that (1) exert their effects at very low concentrations and (2) usually act near their sites of synthesis. These substances include the prostaglandins (PG) (Figure 25.27) as well as thromboxanes (Tx), leukotrienes, and other hydroxyeicosanoic acids. Thromboxanes, discovered in blood platelets (thrombocytes), are cyclic ethers (TxBg is actually a hemiacetal see Figure 25.27) with a hydroxyl group at C-15. 

PG synthesis involves four steps (Figme 2). The first two steps are common to all cells involved in prostaglandin synthesis while the final two steps are cell-specific (14-16). Release of the substrate, arachidonic acid, from membrane phospholipid stores by phospholipase is the initial event in prostaglandin synthesis, and this is followed by formation of the common PG intermediate, PGHj catalyzed by PGH synthase. At this point, rearrangement of PGH to form either stabk (PGD / Ej/ F, ) or unstable (platelet thromboxane - TxA, endothelial prostacyclin - PGy products takes place. The final step, also cell-specific, involves breakdown of the active compounds to irractive metabolites. 

Steps in prostaglandin (PG) biosynthesis PG synthesis involves four steps 1) Release of the substrate, arachidonic acid (20 4), firom membrane phospholipids by a phospholipase. 2) Formation of the common intermediate, PGHj, from arachi-donate by PGH synthase throu sequential cyclo-oxygenase and peroxidase activities, both ofwWch are present within the same enzyme. 3) Fonnation of cell-specific PG products, either "stable" (Dj, E, Fj,) or "imstable" (thromboxane, prostacyclin), by distinct enzymes formd in different cells and tissues. 4) Breakdown of active compoimds to inactive metabolites, using TxAj -> TxB, and PGI -> 6keto PGF as examples. 

Sources of arachidonic acid involved in thromboxane synthesis... 

The eicosanoids are locally active hormones (autocoids) that are derived from precursor polyunsaturated fatty acids. The rate-limiting step in the synthesis of eicosanoids is the phospholipase-regulated release of arachidonic add from membranes. Arachi-donic acid metabolism may follow one of three possible pathways. In the first, the cydooxygenase- peroxidase pathway leads to the formation of the prostenoids - prostaglandins and thromboxanes. In the second, the lipoxygenase pathway yields the leuko-trienes and lipoxins. A third pathway, the cytochrome P-450 mono oxygenase pathway is also involved in the metabolism of arachidonic add. 

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