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
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.[3][4]
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.[5] Under severe conditions of essential fatty acid deprivation, mammals will elongate and desaturate
oleic acid to make mead acid, (20:3, n−9).[6] This has been documented to a lesser extent in vegetarians and semi-vegetarians following an unbalanced diet.[7][8]
Mead acid has been found to decrease
osteoblastic activity. This may be important in treating conditions where inhibition of bone formation is desired.[9]
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.[3]
Mead acid is metabolized by
5-lipoxygenase to 5-hydroxyeicosatrienoic acid (5-HETrE)[11] and then by
5-hydroxyeicosanoid dehydrogenase to 5-oxoeicosatrienoic acid (5-oxo-ETrE).[12]
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;[13]
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.[12]
^
abOliw, E.H.; Hornsten, L.; Sprecher, H.; Hamberg, M. (1993). "Oxygenation of 5,8,11-Eicosatrienoic Acid by Prostaglandin Endoperoxide Synthase and by Cytochrome P450 Monooxygenase: Structure and Mechanism of Formation of Major Metabolites". Archives of Biochemistry and Biophysics. 305 (2): 288–297.
doi:
10.1006/abbi.1993.1425.
PMID8373167.
^Patel, P.; Cossette, C.; Anumolu, J. R.; Gravel, S.; Lesimple, A.; Mamer, O. A.; Rokach, J.; Powell, W. S. (2008). "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 of Pharmacology and Experimental Therapeutics. 325 (2): 698–707.
doi:
10.1124/jpet.107.134908.
ISSN0022-3565.
PMID18292294.
S2CID19936422.