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α-Parinaric acid

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α-Parinaric acid
Structural formula of α-parinaric acid
Space-filling model of the α-parinaric acid molecule
Names
Preferred IUPAC name
(9Z,11E,13E,15Z)-Octadeca-9,11,13,15-tetraenoic acid
Other names
cis-parinaric acid
α-parinaric acid
Identifiers
3D model (JSmol)
ChEBI
ChemSpider
UNII
  • InChI=1S/C18H28O2/c1-2-3-4-5-6-7-8-9-10-11-12-13-14-15-16-17-18(19)20/h3-10H,2,11-17H2,1H3,(H,19,20)/b4-3-,6-5+,8-7+,10-9-checkY
    Key: IJTNSXPMYKJZPR-ZSCYQOFPSA-NcheckY
  • InChI=1/C18H28O2/c1-2-3-4-5-6-7-8-9-10-11-12-13-14-15-16-17-18(19)20/h3-10H,2,11-17H2,1H3,(H,19,20)/b4-3-,6-5+,8-7+,10-9-
    Key: IJTNSXPMYKJZPR-ZSCYQOFPBE
  • O=C(O)CCCCCCC/C=C\C=C\C=C\C=C/CC
Properties
C18H28O2
Molar mass 276.41372
Melting point 85 to 86 °C (185 to 187 °F; 358 to 359 K)
Except where otherwise noted, data are given for materials in theirstandard state(at 25 °C [77 °F], 100 kPa).

α-Parinaric acidis aconjugatedpolyunsaturatedfatty acid.Discovered by Tsujimoto and Koyanagi in 1933,[1]it contains 18 carbon atoms and 4conjugateddouble bonds. The repeatingsingle bond-double bondstructure of α-parinaric acid distinguishes it structurally and chemically from the usual "methylene-interrupted" arrangement ofpolyunsaturated fatty acidsthat have double-bonds and single bonds separated by amethylene unit(−CH2−). Because of thefluorescentproperties conferred by the alternating double bonds, α-parinaric acid is commonly used as a molecular probe in the study ofbiomembranes.

Natural sources

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α-Parinaric acid occurs naturally in the seeds of themakita tree(Parinari laurina), a tree found inFijiand otherPacific islands.Makita seeds contain about 46% α-parinaric acid, 34% α-eleostearic acid as major components, with lesser amounts ofsaturated fatty acids,oleic acidandlinoleic acid.[2]α-Parinaric acid is also found in the seed oil ofImpatiens balsamina,a member of the familyBalsaminaceae.The major fatty acids ofImpatiens balsaminaare 4.7%palmitic acid,5.8%stearic acid,2.8%arachidic acid,18.3% oleic acid, 9.2% linoleic acid, 30.1% linolenic acid and 29.1% α-parinaric acid.[3]It is also present in thefungusClavulina cristata,[4]and the plantSebastiana brasiliensis(familyEuphorbiaceae).[5]

Synthesis

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Biosynthesis

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The biochemical mechanism by which α-parinaric acid is formed in the plantImpatiens balsaminawas elaborated using techniques ofmolecular biology.The enzyme responsible for the creation of the conjugated double bonds was identified usingexpressed sequence tags,and called a "conjugase". This enzyme is related to the family of fatty aciddesaturaseenzymes responsible for putting double bonds into fatty acids.[6]

Chemical synthesis

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α-Parinaric acid may besynthesizedchemically usingα-linolenic acidas a starting compound. This synthesis enables the transformation of 1,4,7-octatriene methylene-interruptedcisdouble bonds of naturally occurring polyunsaturated fatty acids to 1,3,5,7-octatetraenes in high yield.[7]More recently (2008), Lee et al. reported a simple and efficient chemical synthesis using a modular design method called iterative cross-coupling.[8]

Uses

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Membrane probes

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Both the Alpha and beta (alltrans) isomers of parinaric acid are used as molecular probes of lipid-lipid interactions, by monitoringphase transitionsin bilayer lipid membranes.[9]α-Parinaric acid was shown to integrate normally into thephospholipid bilayerof mammalian cells,[10]nervous tissue,[11]with minimal effects on thebiophysicalproperties of the membrane. Molecular interactions with neighboring membrane lipids will affect the fluorescence of α-parinaric acid in predictable ways, and the subsequent subtle changes in energy intensities may be measuredspectroscopically.

Researchers have put α-parinaric to good use in the study of membrane biophysics. For example, it was used to help establish the existence of a "fluidity gradient" across the membrane bilayer of sometumor cells― the inner monolayer of the membrane is less fluid than the outer monolayer.[12]

Lipid-protein interactions

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α-Parinaric acid is also used as achromophoreto study interactions between membrane proteins and lipids. Because of the similarity of α-parinaric acid to normal membrane lipids, it has minimal perturbing influence.[13]By measuring shifts in theabsorption spectrum,enhancement of α-parinaric acidfluorescence,inducedcircular dichroism,and energy transfer betweentryptophanamino acids in the protein and the bound chromophore, information may be gleaned about the molecular interactions between protein and lipid.[13]For example, this technique is used to investigate how fatty acids bind toserum albumin(a highly abundant blood protein),[14][15]lipid transport processes including structural characterization oflipoproteins,[16]andphospholipid-transfer proteins.[17]

Clinical uses

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The concentrations of fatty acids in blood serum orplasmacan be measured using α-parinaric acid, which will compete for binding sites on serum albumin.[18]

Food chemistry

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α-Parinaric acid has been used to study thehydrophobicityandfoamingcharacteristics of food proteins,[19][20]as well as the foam stability of beer.[21]In this latter research, α-parinaric acid was used in a fluorescentassayto assess the lipid–binding potential of the proteins in the beer, as these proteins help protect beer from foam–reducing medium– and long–chain fatty acids.

Cytotoxic effects on tumor cells

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α-Parinaric acid iscytotoxicto humanleukemiacells incell cultureat concentrations of 5μMor less, by sensitizing the tumor cells tolipid peroxidation,the process wherefree radicalsreact with electrons from cell membrane lipids, resulting in cell damage.[22]It is similarly cytotoxic to malignantgliomasgrown in cell culture.[23]Normal (non-tumorous)astrocytesgrown in culture are far less sensitive to the cytotoxic effects of α-parinaric acid.[23]This preferential toxicity towards tumor cells is due to a differential regulation ofc-Jun N-terminal kinase,andforkhead transcription factorsbetween malignant and normal cells.[24]

References

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  1. ^Tsujimoto M, Koyanagi H. (1933). New unsaturated acid in the kernel oil of "akarittom", "Parinarium laurinum". I.Kogyo Kagaku Zasshi36(Suppl): 110–113.
  2. ^Hilditch TP et al. (1964).The Chemical Constitution of Natural Fats, Fourth Edition.pg. 253.
  3. ^Gunstone F.D. (1996).Fatty Acid and Lipid Chemistry.Berlin: Springer Verlag. p. 10.ISBN0-8342-1342-7.
  4. ^Endo S, Zhiping G, Takagi T. (1991). Lipid components of seven species of Basidiomycotina and three species of Ascomycotina.Journal of the Japan Oil Chemists' Society40(7): 574–577.
  5. ^Spitzer V, Tomberg W, Zucolotto M. (1996). Identification of Alpha -parinaric acid in the seed oil ofSebastiana brasiliensisSprengel (Euphorbiaceae).Journal of the American Oil Chemists' Society73(5): 569–573.
  6. ^Cahoon EB, Carlson TJ, Ripp KG, Schweiger BJ, Cook GA, Hall SE, Kinney AJ (October 1999)."Biosynthetic origin of conjugated double bonds: production of fatty acid components of high-value drying oils in transgenic soybean embryos".Proc. Natl. Acad. Sci. U.S.A.96(22): 12935–40.Bibcode:1999PNAS...9612935C.doi:10.1073/pnas.96.22.12935.PMC23170.PMID10536026.
  7. ^Kuklev DV, Smith WL (September 2004). "Synthesis of four isomers of parinaric acid".Chem. Phys. Lipids.131(2): 215–22.doi:10.1016/j.chemphyslip.2004.06.001.PMID15351273.
  8. ^Lee SJ, Gray KC, Paek JS, Burke MD (January 2008)."Simple, efficient, and modular syntheses of polyene natural products via iterative cross-coupling".J. Am. Chem. Soc.130(2): 466–8.doi:10.1021/ja078129x.PMC3107126.PMID18081295.
  9. ^Sklar LA, Hudson BS, Simoni RD (May 1975)."Conjugated polyene fatty acids as membrane probes: preliminary characterization".Proc. Natl. Acad. Sci. U.S.A.72(5): 1649–53.Bibcode:1975PNAS...72.1649S.doi:10.1073/pnas.72.5.1649.PMC432600.PMID1057769.
  10. ^Rintoul DA, Simoni RD (November 1977)."Incorporation of a naturally occurring fluorescent fatty acid into lipids of cultured mammalian cells".J. Biol. Chem.252(22): 7916–8.doi:10.1016/S0021-9258(17)40910-0.PMID914848.
  11. ^Harris WE, Stahl WL (December 1983). "Incorporation of cis-parinaric acid, a fluorescent fatty acid, into synaptosomal phospholipids by an acyl-CoA acyltransferase".Biochim. Biophys. Acta.736(1): 79–91.doi:10.1016/0005-2736(83)90172-4.PMID6580918.
  12. ^Schroeder F (November 1978). "Differences in fluidity between bilayer halves of tumour cell plasma membranes".Nature.276(5687): 528–30.Bibcode:1978Natur.276..528S.doi:10.1038/276528a0.PMID723938.S2CID4371631.
  13. ^abSklar LA, Hudson BS, Simoni RD (November 1977). "Conjugated polyene fatty acids as fluorescent probes: binding to bovine serum albumin".Biochemistry.16(23): 5100–8.doi:10.1021/bi00642a024.PMID911814.
  14. ^Berde CB, Hudson BS, Simoni RD, Sklar LA (January 1979)."Human serum albumin. Spectroscopic studies of binding and proximity relationships for fatty acids and bilirubin".J. Biol. Chem.254(2): 391–400.doi:10.1016/S0021-9258(17)37930-9.PMID216673.
  15. ^Keuper HJK, Klein RA, Spener F. (1985). Spectroscopic investigations on the binding site of bovine hepatic fatty-acid binding protein: evidence for the existence of a single binding site for two fatty-acid molecules.Chemistry and Physics of Lipids38(1–2): 159–174.
  16. ^Ben-Yashar V, Barenholz Y (November 1991). "Characterization of the core and surface of human plasma lipoproteins. A study based on the use of five fluorophores".Chem. Phys. Lipids.60(1): 1–14.doi:10.1016/0009-3084(91)90009-Z.PMID1813177.
  17. ^Kasurinen J, van Paridon PA, Wirtz KW, Somerharju P (September 1990). "Affinity of phosphatidylcholine molecular species for the bovine phosphatidylcholine and phosphatidylinositol transfer proteins. Properties of the sn-1 and sn-2 acyl binding sites".Biochemistry.29(37): 8548–54.doi:10.1021/bi00489a007.PMID2271538.
  18. ^Berde CB, Kerner JA, Johnson JD. (1980). Use of the conjugated polyene fatty-acid parinaric-acid in assaying fatty-acids in serum or plasma.Clinical Chemistry26(8): 1173–1177.
  19. ^Townsend A-A, Nakai S. (1983). Relationships between hydrophobicity and foaming characteristics of food proteins.Journal of Food Science48(2): 588–594.
  20. ^Zhu H, Damodaran S. (1994). Heat-induced conformational changes in whey protein isolate and its relation to foaming properties.Journal of Agricultural and Food Chemistry42(4): 846–855.
  21. ^Cooper DJ, Husband FA, Mills EN, Wilde PJ (December 2002). "Role of beer lipid-binding proteins in preventing lipid destabilization of foam".J. Agric. Food Chem.50(26): 7645–50.doi:10.1021/jf0203996.PMID12475284.
  22. ^Cornelius AS, Yerram NR, Kratz DA, Spector AA (November 1991)."Cytotoxic effect ofcis-parinaric acid in cultured malignant cells ".Cancer Res.51(22): 6025–30.PMID1933865.
  23. ^abTraynelis VC, Ryken TC, Cornelius AS (September 1995). "Cytotoxicity ofcis-parinaric acid in cultured malignant gliomas ".Neurosurgery.37(3): 484–9.doi:10.1097/00006123-199509000-00017.PMID7501114.
  24. ^Zaheer A, Sahu SK, Ryken TC, Traynelis VC (January 2007). "Cis-parinaric acid effects, cytotoxicity, c-Jun N-terminal protein kinase, forkhead transcription factor and Mn-SOD differentially in malignant and normal astrocytes ".Neurochem. Res.32(1): 115–24.doi:10.1007/s11064-006-9236-2.PMID17160503.S2CID630323.
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