Thromboxane structure

An alternative solution is to abandon bioassay entirely and use a more specific approach instead. One such approach in TXA 2 assay is based on the rapid conversion of this unstable compound into a stable derivative by trapping with excess methanol or some other nucleophilic reagent (see above. Elucidation of the thromboxane structure). If methanol is used, the formed products are two epimers of mono-O-methyl TXB2 (Fig. 2). These compounds are biologically inactive but are instead suitable for assay by methods requiring chemical stability of the measured compound, such as gas chromatography mass spectrometry or radioimmunoassay. 

Threonine, stereoisomers of, 302-303 structure and properties of, 1019 Threose. configuration of, 982 molecular model of, 294 Thromboxane B2. structure of,... 

Rats fed a purified nonlipid diet containing vitamins A and D exhibit a reduced growth rate and reproductive deficiency which may be cured by the addition of linoleic, a-linolenic, and arachidonic acids to the diet. These fatty acids are found in high concentrations in vegetable oils (Table 14-2) and in small amounts in animal carcasses. These essential fatty acids are required for prostaglandin, thromboxane, leukotriene, and lipoxin formation (see below), and they also have various other functions which are less well defined. Essential fatty acids are found in the stmctural lipids of the cell, often in the 2 position of phospholipids, and are concerned with the structural integrity of the mitochondrial membrane. 

Lipids have multiple roles in cells. Recent discoveries show that the same lipid may have both structural and regulatory roles in the cell. For example, while arachidonic acid (20 4co6) is a major constituent of brain inositides and PtdEtn, the free acid is also a precursor of a number of important bio messengers, the eicosanoids, such as prostaglandins, prostacyclins, leukotrienes and thromboxanes... 

Dietary polyunsaturated fatty acids (PUFAs), especially the n-3 series that are found in marine fish oils, modulate a variety of normal and disease processes, and consequently affect human health. PUFAs are classified based on the position of double bonds in their lipid structure and include the n-3 and n-6 series. Dietary n-3 PUFAs include a-linolenic acid, eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA) whereas the most common n-6 PUFAs are linoleic acid, y-linolenic acid, and arachidonic acid (AA). AA is the primary precursor of eicosanoids, which includes the prostaglandins, leukotrienes, and thromboxanes. Collectively, these AA-derived mediators can exert profound effects on immune and inflammatory processes. Mammals can neither synthesize n-3 and n-6 PUFAs nor convert one variety to the other as they do not possess the appropriate enzymes. PUFAs are required for membrane formation and function... 

Originally isolated from the prostate gland (hence the name pro sta-gland-in), prostaglandins are chemically simple fatty acid-like molecules (Figure 5.3). Structural differences give rise to several series of structurally different prostaglandins, for example PGE, PGF and thromboxane. 

Figure 11.16 Structure of prostanoate, and three eicosanoids. Structurally, prostaglandins, thromboxanes and prostacyclins may be regarded as derivates of prostanoate, that is, they contain 20 carbon atoms and a saturated five membered ring (cyclopentane).

Figure 11.26 The structures of the prostaglandin E series produced from three polyunsaturated fatty acids containing 20 carbon atoms but a different number of double bonds. The number of double bonds in the three different acids produces prostaglandins of the E series with a different number of double bonds outside the cyclopentane ring. It is this number which influences the function of the prostaglandin and similarly the function of prostacyclins and thromboxanes (see text). Note, PGEi has one double bond, PGE2 has two double bonds and PGE3 has three double bonds outside the cyclopentane ring.

Cyclooxygenase converts arachidonic acid first to prostaglandin G (PGG) and then to PGH prior to formation of prostaglandins, thromboxanes and prostacyclins. The structures of the intermediates and some of the end-products of these conversions are provided in Figure 11.28. 

The fats also have a plastic function as they are included in cell membranes and other cell structures. The central and peripheral nervous systems are rich in lipids. PNFA are included in cell membranes, with their most significant function being the synthesis of cell hormones — prostaglandins. The properties of cell membranes as well as their interaction with external factors depend on the relation of PNFA concentration in cell components. In humans, prostaglandins are created not only in tissues but also in thrombocytes (thromboxanes) and in leucocytes (leukotrienes). The biological action of thrombocytes is extremely variant and depends on PNFA type which are the basis for fatty acid creation. 

M. Takasuka, M. Kishi, M. Yamakawa, FTIR spectral study of intramolecular hydrogen bonding in thromboxane A2 receptor agonist (U-46619), prostaglandin (PG)E2, PGD2, PGF2.alpha., prostacyclin receptor agonist (carbacyclin) and their related compounds in dilute carbon tetrachloride solution Structure-activity relationships, J. Med. Chem. 37 (1994) 47. 

The antiasthamtic activity of the sulfur-free substituted long chain fatty acid seratrodast (59-5) is attributed to the antagonism of thromboxanes, whose structures also include a fatty side chain, rather than to leukotrienes. Friedel-Crafts acylation of benzene with the acid chloride from monomethyl pimelate (59-1) leads to... 

Certain structural indications of thromboxane A2 biosynthesis inhibition and hence potential therapeutic utility in arterial thrombosis prompted the synthesis of the pyridine prostanoid 544 (Scheme 165) (83TL3291). Brief metalation of 42 followed by DMF quench afforded aldehyde 541, which upon Homer-Emmons chain extension, reduction, and protection gave 542. Having served as a DMG, the bromo function was subjected to metal-halogen exchange, transmetalation (CuCN), and condensation with an iodo allene to furnish the 3,4-disubstituted pyridine 543. The latter was transformed into two derivatives 544 (with and without double bond), which were shown to be effective inhibitors of thromboxane A2. 

Examples of prostaglandin structures. Prostaglandins are named as follows PG plus a third letter (for example, A,D,E,F), which designates the type and arrangement of functional groups in the molecule. PGI2 is known as prostacyclin. The subscript number indicates the number of double bonds in the molecule. Thromboxanes are designated by TX and leukotrienes by LT. 

The structure of the thromboxane A2. Thromboxanes differ from prostaglandins in having a cyclic ether (oxane) ring structure. 

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