Wikipedia:WikiProject Chemicals/Chembox validation/VerifiedDataSandbox and Α-Parinaric acid: Difference between pages

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| ImageFile =Alpha-parinaric acid.svg

| ImageSize =260

| ImageAlt = Structural formula of α-parinaric acid

| ImageFile1 = Alpha-Parinaric-acid-3D-spacefill.png

| ImageSize1 =250

| ImageAlt1 = Space-filling model of the α-parinaric acid molecule

| Name =α-Parinaric acid

| PIN =(9''Z'',11''E'',13''E'',15''Z'')-Octadeca-9,11,13,15-tetraenoic acid

| OtherNames =''cis''-parinaric acid<br>α-parinaric acid

|Section1={{Chembox Identifiers

| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}

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| CASNo=593-38-4

| UNII_Ref = {{fdacite|correct|FDA}}

| UNII = PK8M3ENX8C

| PubChem=5460995

|Section2={{Chembox Properties

| Formula=C₁₈H₂₈O₂

| MolarMass=276.41372

| Appearance=

| Density=

| MeltingPtC = 85 to 86

| BoilingPt=

| Solubility=

|Section3={{Chembox Hazards

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'''α-Parinaric acid''' is a [[conjugated fatty acid|conjugated]] polyunsaturated [[fatty acid]]. Discovered by Tsujimoto and Koyanagi in 1933,<ref>Tsujimoto M, Koyanagi H. (1933). New unsaturated acid in the kernel oil of "akarittom", "Parinarium laurinum". I. ''Kogyo Kagaku Zasshi'' '''36''' (Suppl): 110–113.</ref> it contains 18 carbon atoms and 4 [[conjugated system|conjugated]] double bonds. The repeating [[single bond]]-[[double bond]] structure of α-parinaric acid distinguishes it structurally and chemically from the usual "methylene-interrupted" arrangement of [[polyunsaturated fatty acid]]s that have double-bonds and single bonds separated by a [[methylene bridge|methylene unit]] (−CH₂−). Because of the [[fluorescent]] properties conferred by the alternating double bonds, α-parinaric acid is commonly used as a molecular probe in the study of [[biological membranes|biomembranes]].

==Natural sources==

α-Parinaric acid occurs naturally in the seeds of the [[Atuna racemosa racemosa|makita tree]] (''Parinari laurina''), a tree found in [[Fiji]] and other [[Pacific islands]]. Makita seeds contain about 46% α-parinaric acid, 34% α-eleostearic acid as major components, with lesser amounts of [[saturated fatty acid]]s, [[oleic acid]] and [[linoleic acid]].<ref>Hilditch TP et al. (1964). ''The Chemical Constitution of Natural Fats, Fourth Edition.'' pg. 253.</ref> α-Parinaric acid is also found in the seed oil of ''[[Impatiens balsamina]]'', a member of the family [[Balsaminaceae]]. The major fatty acids of ''[[Impatiens balsamina]]'' are 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.<ref name="isbn0-8342-1342-7">{{cite book |author =Gunstone F.D.|title=Fatty Acid and Lipid Chemistry|publisher=Springer Verlag |location=Berlin |year=1996 |page=10 |isbn=0-8342-1342-7}}</ref> It is also present in the [[fungus]] ''[[Clavulina cristata]]'',<ref>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' Society'' '''40'''(7): 574&ndash;577.</ref> and the plant ''Sebastiana brasiliensis'' (family [[Euphorbiaceae]]).<ref>Spitzer V, Tomberg W, Zucolotto M. (1996). Identification of alpha-parinaric acid in the seed oil of ''Sebastiana brasiliensis'' Sprengel (Euphorbiaceae). ''Journal of the American Oil Chemists' Society'' '''73'''(5): 569&ndash;573.</ref>

==Synthesis==

===Biosynthesis===

The biochemical mechanism by which α-parinaric acid is formed in the plant ''[[Impatiens balsamina]]'' was elaborated using techniques of [[molecular biology]]. The enzyme responsible for the creation of the conjugated double bonds was identified using [[expressed sequence tag]]s, and called a "conjugase". This enzyme is related to the family of fatty acid [[desaturase]] enzymes responsible for putting double bonds into fatty acids.<ref name="pmid10536026">{{cite journal |vauthors =Cahoon EB, Carlson TJ, Ripp KG, Schweiger BJ, Cook GA, Hall SE, Kinney AJ |title=Biosynthetic origin of conjugated double bonds: production of fatty acid components of high-value drying oils in transgenic soybean embryos |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=96 |issue=22 |pages=12935–40 |date=October 1999 |pmid=10536026 |pmc=23170 |doi= 10.1073/pnas.96.22.12935|bibcode=1999PNAS...9612935C |doi-access=free }}</ref>

===Chemical synthesis===

α-Parinaric acid may be [[organic synthesis|synthesized]] chemically using [[α-linolenic acid]] as a starting compound. This synthesis enables the transformation of 1,4,7-octatriene methylene-interrupted ''cis'' double bonds of naturally occurring polyunsaturated fatty acids to 1,3,5,7-octatetraenes in high yield.<ref name="pmid15351273">{{cite journal |vauthors =Kuklev DV, Smith WL |title=Synthesis of four isomers of parinaric acid |journal=Chem. Phys. Lipids |volume=131 |issue=2 |pages=215–22 |date=September 2004 |pmid=15351273 |doi=10.1016/j.chemphyslip.2004.06.001 }}</ref> More recently (2008), Lee et al. reported a simple and efficient chemical synthesis using a modular design method called iterative cross-coupling.<ref name="pmid18081295">{{cite journal |vauthors =Lee SJ, Gray KC, Paek JS, Burke MD |title=Simple, efficient, and modular syntheses of polyene natural products via iterative cross-coupling |journal=J. Am. Chem. Soc. |volume=130 |issue=2 |pages=466–8 |date=January 2008 |pmid=18081295 |doi=10.1021/ja078129x |pmc=3107126}}</ref>

==Uses==

===Membrane probes===

Both the alpha and beta (all ''trans'') isomers of parinaric acid are used as molecular probes of lipid-lipid interactions, by monitoring [[phase transition]]s in bilayer lipid membranes.<ref name="pmid1057769">{{cite journal |vauthors =Sklar LA, Hudson BS, Simoni RD |title=Conjugated polyene fatty acids as membrane probes: preliminary characterization |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=72 |issue=5 |pages=1649–53 |date=May 1975 |pmid=1057769 |pmc=432600 |doi= 10.1073/pnas.72.5.1649|bibcode=1975PNAS...72.1649S |doi-access=free }}</ref> α-Parinaric acid was shown to integrate normally into the [[lipid bilayer|phospholipid bilayer]] of mammalian cells,<ref name="pmid914848">{{cite journal |vauthors=Rintoul DA, Simoni RD |title=Incorporation of a naturally occurring fluorescent fatty acid into lipids of cultured mammalian cells |journal=J. Biol. Chem. |volume=252 |issue=22 |pages=7916–8 |date=November 1977 |doi=10.1016/S0021-9258(17)40910-0 |pmid=914848 |doi-access=free }}</ref> nervous tissue,<ref name="pmid6580918">{{cite journal |vauthors =Harris WE, Stahl WL |title=Incorporation of cis-parinaric acid, a fluorescent fatty acid, into synaptosomal phospholipids by an acyl-CoA acyltransferase |journal=Biochim. Biophys. Acta |volume=736 |issue=1 |pages=79–91 |date=December 1983 |pmid=6580918 |doi= 10.1016/0005-2736(83)90172-4}}</ref> with minimal effects on the [[biophysical]] properties 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 measured [[spectroscopy|spectroscopically]].

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 some [[tumor cell]]s ― the inner monolayer of the membrane is less fluid than the outer monolayer.<ref name="pmid723938">{{cite journal |author =Schroeder F|title=Differences in fluidity between bilayer halves of tumour cell plasma membranes |journal=Nature |volume=276 |issue=5687 |pages=528–30|date=November 1978 |pmid=723938 |doi= 10.1038/276528a0|bibcode=1978Natur.276..528S |s2cid=4371631 }}</ref>

===Lipid-protein interactions===

α-Parinaric acid is also used as a [[chromophore]] to study interactions between membrane proteins and lipids. Because of the similarity of α-parinaric acid to normal membrane lipids, it has minimal perturbing influence.<ref name="pmid911814">{{cite journal |vauthors =Sklar LA, Hudson BS, Simoni RD |title=Conjugated polyene fatty acids as fluorescent probes: binding to bovine serum albumin |journal=Biochemistry |volume=16 |issue=23 |pages=5100–8 |date=November 1977 |pmid=911814 |doi= 10.1021/bi00642a024}}</ref> By measuring shifts in the [[absorption spectrum]], enhancement of α-parinaric acid [[fluorescence]], induced [[circular dichroism]], and energy transfer between [[tryptophan]] amino acids in the protein and the bound chromophore, information may be gleaned about the molecular interactions between protein and lipid.<ref name="pmid911814"/> For example, this technique is used to investigate how fatty acids bind to [[serum albumin]] (a highly abundant blood protein),<ref name="pmid216673">{{cite journal |vauthors=Berde CB, Hudson BS, Simoni RD, Sklar LA |title=Human serum albumin. Spectroscopic studies of binding and proximity relationships for fatty acids and bilirubin |journal=J. Biol. Chem. |volume=254 |issue=2 |pages=391–400 |date=January 1979 |doi=10.1016/S0021-9258(17)37930-9 |pmid=216673 |doi-access=free }}</ref><ref>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 Lipids'' '''38'''(1&ndash;2): 159&ndash;174.</ref> lipid transport processes including structural characterization of [[lipoprotein]]s,<ref name="pmid1813177">{{cite journal |vauthors =Ben-Yashar V, Barenholz Y |title=Characterization of the core and surface of human plasma lipoproteins. A study based on the use of five fluorophores |journal=Chem. Phys. Lipids |volume=60 |issue=1 |pages=1–14 |date=November 1991 |pmid=1813177 |doi= 10.1016/0009-3084(91)90009-Z}}</ref> and [[phospholipid]]-transfer proteins.<ref name="pmid2271538">{{cite journal |vauthors =Kasurinen J, van Paridon PA, Wirtz KW, Somerharju P |title=Affinity of phosphatidylcholine molecular species for the bovine phosphatidylcholine and phosphatidylinositol transfer proteins. Properties of the sn-1 and sn-2 acyl binding sites |journal=Biochemistry |volume=29 |issue=37 |pages=8548–54 |date=September 1990 |pmid=2271538 |doi= 10.1021/bi00489a007}}</ref>

===Clinical uses===

The concentrations of fatty acids in blood serum or [[blood plasma|plasma]] can be measured using α-parinaric acid, which will compete for binding sites on serum albumin.<ref>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 Chemistry'' '''26'''(8): 1173&ndash;1177.</ref>

===Food chemistry===

α-Parinaric acid has been used to study the [[hydrophobicity]] and [[foaming agent|foaming]] characteristics of food proteins,<ref>Townsend A-A, Nakai S. (1983). Relationships between hydrophobicity and foaming characteristics of food proteins. ''Journal of Food Science'' '''48'''(2): 588&ndash;594.</ref><ref>Zhu H, Damodaran S. (1994). Heat-induced conformational changes in whey protein isolate and its relation to foaming properties. ''Journal of Agricultural and Food Chemistry'' '''42'''(4): 846&ndash;855.</ref> as well as the foam stability of beer.<ref name="pmid12475284">{{cite journal |vauthors =Cooper DJ, Husband FA, Mills EN, Wilde PJ |title=Role of beer lipid-binding proteins in preventing lipid destabilization of foam |journal=J. Agric. Food Chem. |volume=50 |issue=26 |pages=7645–50 |date=December 2002 |pmid=12475284|doi=10.1021/jf0203996}}</ref> In this latter research, α-parinaric acid was used in a fluorescent [[assay]] to 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==

α-Parinaric acid is [[cytotoxicity|cytotoxic]] to human [[leukemia]] cells in [[cell culture]] at concentrations of 5 [[Micromolar#Molarity|μM]] or less, by sensitizing the tumor cells to [[lipid peroxidation]], the process where [[free radical]]s react with electrons from cell membrane lipids, resulting in cell damage.<ref name="pmid1933865">{{cite journal |vauthors =Cornelius AS, Yerram NR, Kratz DA, Spector AA |title=Cytotoxic effect of ''cis''-parinaric acid in cultured malignant cells |journal=Cancer Res. |volume=51 |issue=22 |pages=6025–30 |date=November 1991 |pmid=1933865 |url=http://cancerres.aacrjournals.org/cgi/pmidlookup?view=long&pmid=1933865}}</ref> It is similarly cytotoxic to malignant [[glioma]]s grown in cell culture.<ref name="pmid7501114">{{cite journal |vauthors =Traynelis VC, Ryken TC, Cornelius AS |title=Cytotoxicity of ''cis''-parinaric acid in cultured malignant gliomas |journal=Neurosurgery |volume=37 |issue=3 |pages=484–9 |date=September 1995 |pmid=7501114 |doi= 10.1097/00006123-199509000-00017}}</ref> Normal (non-tumorous) [[astrocyte]]s grown in culture are far less sensitive to the cytotoxic effects of α-parinaric acid.<ref name="pmid7501114" /> This preferential toxicity towards tumor cells is due to a differential regulation of [[c-Jun N-terminal kinases|c-Jun N-terminal kinase]], and [[FOX proteins|forkhead transcription factors]] between malignant and normal cells.<ref name="pmid17160503">{{cite journal |vauthors =Zaheer A, Sahu SK, Ryken TC, Traynelis VC |title=''Cis''-parinaric acid effects, cytotoxicity, c-Jun N-terminal protein kinase, forkhead transcription factor and Mn-SOD differentially in malignant and normal astrocytes |journal=Neurochem. Res. |volume=32 |issue=1 |pages=115–24 |date=January 2007 |pmid=17160503 |doi=10.1007/s11064-006-9236-2 |s2cid=630323 }}</ref>

==References==

{{reflist}}

{{Fatty acids}}

{{DEFAULTSORT:Parinaric acid, alpha-}}

[[Category:Fatty acids]]

[[Category:Alkenoic acids]]

[[Category:Polyenes]]