Arachidonic concentration

Figure 5. Proposed structures of hydroperoxides formed in arachidonate (20 4) aqueous solutions (pH = 10.5) submitted to y-rays. Monohydroperoxides (6 isomers in positions 5, 8, 9, 11, 12, 15) are formed in micellar medium (high arachidonate concentration) whereas monocyclic and bicyclic hydroperoxides, together with dihydroperoxides are produced in dispersed monomers (low arachidonate concentration) [18],...

The values in this table represent the values (in juM) for the ICjq and the arachidonate concentration used in the assay the letter designates the reference indicated below. Thus, 204/330/d indicates that an lCj(, value of 204 jiM was obtained when 330 jtM archidonate were used as cited by Taylor and Salata [72]. Abbreviations indicate tissues for which the archidonate concentration was not specified BSV, bovine seminal vesicles HRS, human rheumatoid synovium cell, MC5-5 cell line. 

Detailed accounts of the biosynthesis of the prostanoids have been pubUshed (14—17). Under normal circumstances arachidonic acid (AA) is the most abundant C-20 fatty acid m vivo (18—21) which accounts for the predominance of the prostanoids containing two double bonds eg, PGE2 (see Fig. 1). Prostanoids of the one and three series are biosynthesized from dihomo-S-linolenic and eicosapentaenoic acids, respectively. Concentrations ia human tissue of the one-series precursor, dihomo-S-linolenic acid, are about one-fourth those of AA (22) and the presence of PGE has been noted ia a variety of tissues (23). The biosynthesis of the two-series prostaglandins from AA is shown ia Eigure 1. These reactions make up a portion of what is known as the arachidonic acid cascade. Other Hpid products of the cascade iaclude the leukotrienes, lipoxins, and the hydroxyeicosatetraenoic acids (HETEs). Collectively, these substances are termed eicosanoids. 

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. 

Cyclooxygenase (COX) activity is responsible for the formation of prostaglandins from their arachidonic acid precursor. Two COX isoforms have been identified, COX-1 and COX-2. While COX-1 is constitutively expressed in most tissues, COX-2 is typically only found after induction by proinflammatory stimuli. However, a constitutively expressed and highly regulated COX-2 is found in the kidney, both in the renal medulla and in the renal cortex. Renal cortical COX-2 is located in the area ofthe juxtaglomerular apparatus, and prostaglandins formed by COX-2 regulate the expression and secretion of renin in response to a reduction in NaCl concentration at the macula densa. 

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. 

The main problem with any study of prostaglandins (PGs) is that although brain concentrations can exceed 0.1 /rg/g, they appear to be formed on demand, rather than preformed and stored and they have very short half-lives (seconds). Also specific effective antagonists remain to be developed and PGs are widely and evenly distributed, unlike many NTs. Thus any analysis of their central effects rests heavily on either studying PG release, or their effects when applied directly (icv injection). Certainly the brain has the enzymatic ability to synthesise both prostaglandins (cycloxygenase) and leukotrienes (lypoxygenase) from arachidonic acid (AA) (see Fig. 13.8) and a number of central functions have been proposed for them (see Piomelli 1994). 

Hammarstrom, S., Hamberg, M., Samuelsson, B., Duell, E.A., Stawiski, M. and Voorhees, J.J. (1975). Increased concentrations of non-esterified arachidonic acid, 12L-hydroxy-5,8,10,14-eicosatetraenoic acid, prostaglandin E2 and prostaglandin F2 in epidermis of psoriasis. Proc. Natl Acad. Sci. USA 72, 5130-5134. 

Essential fatty acid deficiency Deficiency of linoleic acid, linolenic acid, and/or arachidonic acid, characterized by hair loss, thinning of skin, and skin desquamation. Long-chain fatty acids include trienes (containing three double-bonds [e.g., 5,8,11-eicosatrienoic acid, or Mead acid trienoic acids) and tetraenes (containing four doublebonds [e.g., arachidonic acid]). Biochemical evidence of essential fatty acid deficiency includes a trieneitetraene ratio greater than 0.4 and low linoleic or arachidonic acid plasma concentrations. 

Figure 3. Induction of mutation in Sj typhimurium TA98 by BP-7,8-dihydrodiol, arachidonic acid, and ram seminal vesicle microsomes. Concentration dependence on BP-7,8-dihydro-diol. (Reproduced with permission from Ref. 22. Copyright 1978 Academic.)...

Figure 7. Dependence of BP oxidation by ram seminal vesicle micro-somes on the concentration of different hydroperoxides. Abbreviations used are 20 4, arachidonic acid 15-HPEA, 15-hydroperoxy-eicosatetraenoic acid t-BuOOH, t-butyl hydroperoxide. The structure is PGG2 is given in Figure 1.

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