Fatty acids acetylenic

Leucetta microraphis [413]. Taurospongin A (485) is a sulfated acetylenic fatty acid derivative from Hippospongia sp. from Okinawa. It inhibits both DNA polymerase b and HIV reverse transcriptase [414]. 

There is a seemingly endless variety of fatty acids, but only a few of them predominate in any single organism. Most fatty acid chains contain an even number of carbon atoms. In higher plants the C16 palmitic acid and the C18 unsaturated oleic and linoleic acids predominate. The C18 saturated stearic acid is almost absent from plants and C20 to C24 acids are rarely present except in the outer cuticle of leaves. Certain plants contain unusual fatty acids which may be characteristic of a taxonomic group. For example, the Compositae (daisy family) contain acetylenic fatty acids and the castor bean contains the hydroxy fatty acid ricinoleic acid. 

Brantley SE, Molinski TF, Preston CM, DeLong EF (1995) Brominated Acetylenic Fatty Acids from Xestospongia sp., a Marine Sponge-Bacteria Association. Tetrahedron 51 7667... 

Pham NB, Butler MS, Hooper JNA, Moni RW, Quinn RJ (1992) Isolation of Xestosterol Esters of Brominated Acetylenic Fatty Acids from the Marine Sponge Xestospongia testudinaria. J Nat Prod 62 1439... 

P450IVA1 Rat LAto Clofibrate Terminal acetylenic fatty acids Laurie acid 12-hydroxylase... 

The acetylenic fatty acids 15-hexadec5moic (15-HDYA) and 17-ODYA have also been explored as modulators of leukotriene (LTB ), an important and clinically relevant inflammatory mediator, and its physiologically active (o-hydroxylated metabolite . Both 15-HDYA and 17-ODYA inactivated the polymorphonuclear leukocytic LTB whole cells and cell lysates . In contrast, the shorter-chain acid, 10-undecynoic acid was much less effective, while the saturated analogs of 15-HDYA and 17-ODYA were inactive. 15-HDYA and 17-ODYA also inactivate pulmonary prostaglandin (o-hydroxylases . 

Finally, since fatty acid hydroxylations at the o), 00-1, 00-2, 00-3, and co-4 positions also occur in plants and bacteria °, acetylenic fatty acids have also been employed to examine whether these hydroxylases are mechanistically similar to their mammalian counterparts and/or to identify the role of specific plant and bacterial P450 enzymes °. Thus, midchain and terminal acetylenes such as 10-dodecynoic acid have been used as probes of plant lauric acid oo-hydroxylases . Similarly, 17-ODYA has been shown to inactivate P450g, 3 (CYP108), an enzyme that hydroxylates fatty acids at positions other than the terminal (oo) carbon, through a heme alkylation mechanism . 

CaJacob, C.A., W. Chan, E. Shephard, and P.R. Ortiz de Monteliano (1988). The catalytic site of rat hepatic lauric acid w-hydroxylase. Protein vs prosthetic heme alkylation in the w-hydroxylation of acetylenic fatty acids. J. Biol Chem. 263, 18640-18649. 

Ortiz de Montellano, P.R. and N.O. Reich (1984). Specific inactivation of hepatic fatty acid hydroxylases by acetylenic fatty acids. J. Biol. Chem. 259, 4136-4141. 

Shak, S., N.O. Reich, I.M. Goldstein, and P.R. Ortiz de Montellano (1985). Leukotriene B4 (o-hydroxylase in human polymorphonuclear leukocytes Suicidal inactivation by acetylenic fatty acids. J Biol. Chem. 260, 13023-13028. 

Williams, D.E., A.S. Muerhoff, N.O. Reich, C.A. CaJacob, P.R. Ortiz de Montellano, and B.S.S. Masters (1989). Prostaglandin and fatty acid o) and (co-l) oxidation in rabbit lung. Acetylenic fatty acid mechanism based inactivators as specific inhibitors. J. Biol. Chem. 264, 749-756. 

Substituted imidazoles have been used as inhibitors in vitro. Presumably some acetylenic fatty acids might be inhibitors but no studies have been reported. 

S. Pisch, U.T. Bornscheuer, H.H. Meyer, and R.D. Schmid Properties of unusual phospholipids rV chemoenzymatic synthesis of phospholipids bearing acetylenic fatty acids. Tetrahedron 53 (1997) 14627-14634. 

The acetylenic analog of Mead Acid, 5,8,11-eicosatriynoic acid, was reported to be a selective inhibitor of platelet 12-lipoxygenase. Acetylenic fatty acids also inhibited 15-lipoxygenases of plant (soybean) as well as of animal (rabbit reticulocyte) origin. The nature of the acetylenic compound significantly affected its activity on the soybean enzyme, but not the rabbit enzyme. For the former, 7,10,13-eicosatriynoic acid was the most powerful inactivator. Addition of a fourth triple bond at position 4 or 5 strongly reduced the rate of inactivation. On the other hand, the rabbit reticulocyte enzyme was inactivated almost equally well by the various acetylenic fatty acids that were tried. The mechanism of inactivation of lipoxygenases was also suicide inhibition . ... 

Diedrich, M. and Henschel, K.P. 1991b. The natural occurrence of unusual fatty acids. 3. Acetylenic fatty acids, Nahrung, 35, 193-202. 

Acetylenic fatty acids are substrate analogs which provide unusual insight into the interaction of fatty acids with the cyclooxygenase active site. They exhibit both competitive and non-competitive aspects. All of the 18- and 20-carbon acetylenic acids examined [81,10] exhibited a reversible interaction at the active site competitive with arachidonate (/f, = 2 to 20 juM). 

The main biosynthetic route to acetylenic fatty acids in plants appears to be by enzyme-catalyzed oxidation of analogous compounds with carbon-carbon double bonds. The enzymes responsible (acetylenases) belong to a class called desaturases. 

The reactions in Scheme 1.2 are enzyme-mediated. The conversion of arachidonic acid to PGG2 is controlled by the enzyme cyclo-oxygenase. This reaction starts by removal of the pro-5 hydrogen at C-13 and the oxygen atoms subsequently attached at C-9 and C-11 come from the same oxygen molecule. A second molecule enters into the hydroperoxide at C-15. The reaction is inhibited by non-steroidal anti-inflammatory agents such as aspirin and also by several acetylenic fatty acids. 

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