Essential fatty acid interactions
[1] It sits at the head of the "arachidonic acid cascade," which initiates 20 different signalling pathways that control a wide array of biological functions, including inflammation, cell growth, and the central nervous system.
[2][3] Most AA in the human body is derived from dietary linoleic acid (18:2 ω-6), which is found in nuts, seeds, vegetable oils, and animal fats.
These two parallel cascades soften the inflammatory-promoting effects of specific eicosanoids made from AA.
The plasma membranes of cells contain phospholipids, composed of a hydrophilic phosphate head and two hydrophobic fatty acid tails.
[citation needed] In response to various inflammatory signals, these EFAs are cleaved out of the phospholipid and released as free fatty acids.
[citation needed] Cyclooxygenase (COX) oxidation removes two C=C double bonds, leading to the TX, PG, and PGI series.
Cyberlipid Center's Prostenoid page[11] illustrates the parent compound and the rings associated with each series letter.
[14]) Figure 2 shows the ω-3 and -6 synthesis chains, along with the major eicosanoids from AA, EPA, and DGLA.
Dietary ω-3 and GLA counter the inflammatory effects of AA's eicosanoids in three ways: displacement, competitive inhibition, and direct counteraction.
[23] Studies have shown that dietary oxidized linoleic acid (LA, 18:2 ω-6) has inflammatory properties.
Some observations partially explain this paradox: LA competes with α-linolenic acid (ALA, 18:3 ω-3) for Δ6-desaturase and thereby eventually inhibits the formation of anti-inflammatory EPA (20:5 ω-3).
Dietary GLA leads to sharply increased DGLA in the white blood cells' membranes, whereas LA does not.
Many immune system cells express multiple receptors that couple these apparently opposing pathways.
The arachidonic acid cascade is arguably the most elaborate signaling system neurobiologists have to deal with.
They activate phospholipids to release AA from neuron cell membranes as a free fatty acid.
[citation needed] During its short lifespan, free AA may affect the activity of the neuron's ion channels and protein kinases.
Or it may be metabolized to form eicosanoids, epoxyeicosatrienoic acids (EETs), neuroprotectin D, or various endocannabinoids (anandamide and its analogs).
Neurons in the CNS are organized as interconnected groups of functionally related cells (e.g. in sensory systems).
Furthermore, during development and in certain forms of learning, postsynaptic cells may secrete regulatory factors that diffuse back to the presynaptic component, determining its survival as an active terminal, the amplitude of its sprouting, and its efficacy in secreting neurotransmitters—a phenomenon known as retrograde regulation.
Studies have proposed that arachidonic acid metabolites participate in retrograde signaling and other forms of local modulation of neuronal activity.
To act, 5-LO uses the nuclear-membrane enzyme 5-lipoxygenase-activating protein (FLAP), first to a hydroperoxyeicosatetraenoic acid (HPETE), then to the first leukotriene, LTA.
