Mead acid
{{Use mdy dates|date=October 2014}}
{{chembox
| Verifiedfields = changed
| Watchedfields = changed
| verifiedrevid = 439734690
| ImageFile=Mead acid.png
| ImageSize=200px
| PIN=(5Z,8Z,11Z)-Icosa-5,8,11-trienoic acid
| OtherNames=
|Section1={{Chembox Identifiers
| CASNo_Ref = {{cascite|correct|CAS}}
| CASNo= 20590-32-3
| UNII_Ref = {{fdacite|changed|FDA}}
| UNII = JQS194YH3X
| PubChem=5312531
| SMILES=CCCCCCCC\C=C/C\C=C/C\C=C/CCCC(=O)O
| ChemSpiderID_Ref = {{chemspidercite|changed|chemspider}}
| ChemSpiderID = 4471956
| InChI = 1/C20H34O2/c1-2-3-4-5-6-7-8-9-10-11-12-13-14-15-16-17-18-19-20(21)22/h9-10,12-13,15-16H,2-8,11,14,17-19H2,1H3,(H,21,22)/b10-9-,13-12-,16-15-
| InChIKey = UNSRRHDPHVZAHH-YOILPLPUBD
| StdInChI_Ref = {{stdinchicite|changed|chemspider}}
| StdInChI = 1S/C20H34O2/c1-2-3-4-5-6-7-8-9-10-11-12-13-14-15-16-17-18-19-20(21)22/h9-10,12-13,15-16H,2-8,11,14,17-19H2,1H3,(H,21,22)/b10-9-,13-12-,16-15-
| StdInChIKey_Ref = {{stdinchicite|changed|chemspider}}
| StdInChIKey = UNSRRHDPHVZAHH-YOILPLPUSA-N
| RTECS =
| MeSHName =
| ChEBI_Ref = {{ebicite|changed|EBI}}
| ChEBI = 72865
}}
|Section2={{Chembox Properties
| Formula=C20H34O2
| MolarMass=306.48276
| Appearance=
| Density=
| MeltingPt=
| BoilingPt=
| Solubility=
}}
|Section3={{Chembox Hazards
| MainHazards=
| FlashPt=
| AutoignitionPt =
}}
}}
Mead acid is an omega-9 fatty acid, first characterized by James F. Mead.{{cite book | last1=Siegel | first1=George J. |last2=Albers | first2=R. Wayne | title=Basic neurochemistry: molecular, cellular, and medical aspects, Volume 1 | page=40 |edition=7th | year=2006 | publisher=Elsevier | url=https://books.google.com/books?id=Af0IyHtGCMUC&q=James+Mead+mead+acid&pg=PA40 | quote=One of these is 20:3ω9, termed 'Mead acid' after its discovery by James Mead....| isbn=9780080472072 }} As with some other omega-9 polyunsaturated fatty acids, animals can make Mead acid de novo. Its elevated presence in the blood is an indication of essential fatty acid deficiency.{{cite journal |url=https://www.sciencedirect.com/science/article/pii/S1388198113002369 |date=January 2014 |volume=1841 |issue=1 |pages=204–213 |title=Identification of genes and pathways involved in the synthesis of Mead acid (20:3n−9), an indicator of essential fatty acid deficiency |author1=Ichi I |author2=Kono N |author3=Arita Y |author4=Haga S |journal=Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids |doi=10.1016/j.bbalip.2013.10.013|pmid=24184513|url-access=subscription }} Mead acid is found in large quantities in cartilage.
Chemistry
Mead acid, also referred to as eicosatrienoic acid, is chemically a carboxylic acid with a 20-carbon chain and three methylene-interrupted cis double bonds, as is typical for polyunsaturated fatty acids. The first double bond is located at the ninth carbon from the omega end. In physiological literature, it is given the name 20:3 (n-9). (See {{slink|Fatty acid|Nomenclature}} for an explanation of the naming system.) In the presence of lipoxygenase, cytochrome p450, or cyclooxygenase, mead acid can form various hydroxyeicosatetraenoic acid (HETE) and hydroperoxy (HpETE) products.{{Cite journal |last1=Oliw |first1=E.H. |last2=Hornsten |first2=L. |last3=Sprecher |first3=H. |last4=Hamberg |first4=M. |date=1993 |title=Oxygenation of 5,8,11-Eicosatrienoic Acid by Prostaglandin Endoperoxide Synthase and by Cytochrome P450 Monooxygenase: Structure and Mechanism of Formation of Major Metabolites |journal=Archives of Biochemistry and Biophysics |language=en |volume=305 |issue=2 |pages=288–297 |doi=10.1006/abbi.1993.1425 |pmid=8373167}}{{cite web
| title=PROSTAGLANDINS AND RELATED COMPOUNDS
| url= http://www.cyberlipid.org/prost1/pros0002.htm
| archive-url=https://web.archive.org/web/20180413060119/http://www.cyberlipid.org/prost1/pros0002.htm
| archive-date=April 13, 2018
| url-status=dead
|author= Cyberlipid Center
|access-date=2007-10-24}}
Physiology
Two fatty acids, linoleic acid and alpha-linolenic acid, are considered essential fatty acids (EFAs) in humans and other mammals. Both are 18 carbon fatty acids unlike mead acid, which has 20 carbons. Linoleic is an ω-6 fatty acid whereas linolenic is ω-3 and mead is ω-9. One study examined patients with intestinal fat malabsorption and suspected EFA deficiency; they were found to have blood-levels of mead acid about 13-fold higher than reference subjects.{{cite journal |url=http://www.clinchem.org/cgi/reprint/33/10/1869 |journal=Clinical Chemistry |volume=33 |pages=1869–1873 |date=October 1, 1987 |title=Criteria for essential fatty acid deficiency in plasma as assessed by capillary column gas–liquid chromatography |author1=EN Siguel |author2=KM Chee |author3=JX Gong |author4=EJ Schaefer |access-date=2007-10-24 |issue=10 |doi=10.1093/clinchem/33.10.1869 |pmid=3665042 |archive-url=https://web.archive.org/web/20110927014210/http://www.clinchem.org/cgi/reprint/33/10/1869 |archive-date=September 27, 2011 |url-status=dead |doi-access=free |url-access=subscription }} Under severe conditions of essential fatty acid deprivation, mammals will elongate and desaturate oleic acid to make mead acid, (20:3, n−9).{{cite book|vauthors = Geissler C, Powers H|title = Human Nutrition|year=2017|publisher = Oxford University Press|isbn =9 78-0-19-876802-9|page=174}} This has been documented to a lesser extent in vegetarians and semi-vegetarians following an unbalanced diet.{{cite journal |vauthors = Phinney SD, Odin RS, Johnson SB, Holman RT |title = Reduced arachidonate in serum phospholipids and cholesteryl esters associated with vegetarian diets in humans |journal = Am. J. Clin. Nutr. |volume = 51 |issue = 3 |pages = 385–92 |year = 1990 |pmid = 2106775|doi = 10.1093/ajcn/51.3.385 }}
{{cite journal
| date=September 2007
| journal=Fats of Life Newsletter
| title= Essential Polyunsaturated Fatty Acids and Early Human Development
| first=Gerard
| last=Hornstra
| access-date=2007-10-23
| url=http://www.fatsoflife.com/pufa/article.asp?nid=1&edition=this&id=484
| archive-url=https://web.archive.org/web/20080607194856/http://www.fatsoflife.com/pufa/article.asp?nid=1&edition=this&id=484
| archive-date=June 7, 2008
}}
Mead acid has been found to decrease osteoblastic activity. This may be important in treating conditions where inhibition of bone formation is desired.{{cite journal|last1=Hamazaki|first1=Tomohito|last2=Suzuki|first2=Nobuo|last3=Widyowati|first3=Retno|last4=Miyahara|first4=Tatsuro|last5=Kadota|first5=Shigetoshi|last6=Ochiai|first6=Hiroshi|last7=Hamazaki|first7=Kei|title=The Depressive Effects of 5,8,11-Eicosatrienoic Acid (20:3n-9) on Osteoblasts|journal=Lipids|volume=44|issue=2|year=2008|pages=97–102|issn=0024-4201|doi=10.1007/s11745-008-3252-8|pmid=18941818|s2cid=4011759}}
Role in inflammation
Cyclooxygenases are enzymes known to play a large role in inflammatory processes through oxidation of unsaturated fatty acids, most notably, the formation of prostaglandin H2 from arachidonic acid (AA). AA has the same chain length as Mead acid but an additional ω-6 double bond. When physiological levels of arachidonic acid are low, other unsaturated fatty acids including mead and linoleic acid are oxidized by COX. Cyclooxygenase breaks the bisallylic C-H bond of AA to synthesize prostaglandin H2, but breaks a stronger allylic C-H bond when it encounters Mead acid instead.
Mead acid is also converted to leukotrienes C3 and D3.{{cite journal |vauthors = Hammarström S|title=Conversion of 5,8,11-Eicosatrienoic Acid to Leukotrienes C3 and D3|journal = Journal of Biological Chemistry|volume=256 |issue = 3 |year = 1981 |pages=2275–2279 |doi=10.1016/S0021-9258(19)69773-5|pmid=6780563 |url = http://www.jbc.org/content/256/5/2275.full.pdf|doi-access = free}}
Mead acid is metabolized by 5-lipoxygenase to 5-hydroxyeicosatrienoic acid (5-HETrE){{cite journal |vauthors = Wei YF, Evans RW, Morrison AR, Sprechert H, Jakschik BA |title = Double bond requirement for the 5-lipoxygenase pathway |journal = Prostaglandins |volume = 29 |issue = 4 |pages = 537–45 |year = 1985 |pmid = 2988021 |doi=10.1016/0090-6980(85)90078-4}} and then by 5-hydroxyeicosanoid dehydrogenase to 5-oxoeicosatrienoic acid (5-oxo-ETrE).{{cite journal|last1=Powell|first1=William S.|last2=Rokach|first2=Joshua|title=The eosinophil chemoattractant 5-oxo-ETE and the OXE receptor|journal=Progress in Lipid Research|volume=52|issue=4|year=2013|pages=651–665|issn=0163-7827|doi=10.1016/j.plipres.2013.09.001|pmid=24056189|pmc=5710732}}
5-Oxo-ETrE is as potent as its arachidonic acid-derived analog, 5-oxo-eicosatetraenoic acid (5-oxo-ETE), in stimulating human blood eosinophils and neutrophils;{{cite journal|last1=Patel|first1=P.|last2=Cossette|first2=C.|last3=Anumolu|first3=J. R.|last4=Gravel|first4=S.|last5=Lesimple|first5=A.|last6=Mamer|first6=O. A.|last7=Rokach|first7=J.|last8=Powell|first8=W. S.|title=Structural Requirements for Activation of the 5-Oxo-6E,8Z, 11Z,14Z-eicosatetraenoic Acid (5-Oxo-ETE) Receptor: Identification of a Mead Acid Metabolite with Potent Agonist Activity|journal=Journal of Pharmacology and Experimental Therapeutics|volume=325|issue=2|year=2008|pages=698–707|issn=0022-3565|doi=10.1124/jpet.107.134908|pmid=18292294|s2cid=19936422}}
it presumably does so by binding to the 5-oxo-ETE receptor (OXER1) and therefore may be, like 5-oxo-ETE, a mediator of human allergic and inflammatory reactions.
See also
- Polyunsaturated fat – lists of ω-3 and ω-6 fatty acids; some others.
- Eicosanoid
- Prostaglandin