For introductory details to this topic, including terminology and ω-3 / ω-6 nomenclature, see Essential fatty acid and Eicosanoid.
Fatty acid breakdown
There is a wide variety of fatty acids found in nature. Two classes of fatty acids are considered essential, the omega-3 and omega-6 fatty acids. Essential fatty acids are necessary for humans but cannot be synthesized by the body and must therefore be obtained from food. Omega-3 and omega-6 are used in some cellular signaling pathways and are involved in mediating inflammation, protein synthesis, and metabolic pathways in the human body.
Eicosanoids are signaling molecules derived from the essential fatty acids (EFAs). They are a major pathway by which the EFAs act in the body. There are four classes of eicosanoid and two or three series within each class. The plasma membranes of cells contain phospholipids, composed of a hydrophilic phosphate head and two hydrophobic fatty acid tails. Some of these fatty acids are 20-carbon polyunsaturated essential fatty acids (AA, EPA, or DGLA). EFAs are cleaved out of the phospholipid and released as free fatty acids. The EFA is oxygenated (by either of two pathways) and further modified, yielding the eicosanoids.
After oxidation, the eicosanoids are further modified, making a series. Members of a series are differentiated by a letter and are numbered by the number of double bonds, which does not change within a series. For example, cyclooxygenase action upon AA (with 4 double bonds) leads to the series-2 thromboxanes[2] (TXA2, TXB2... ), each with two double bonds. Cyclooxygenase action on EPA (with 5 double bonds) leads to the series-3 thromboxanes (TXA3, TXB3, etc.), each with three double bonds. There are exceptions to this pattern, some of which indicate stereochemistry (PGF2α).
Table (1) shows these sequences for AA (20:4 ω-6). The sequences for EPA (20:5 ω-3) and DGLA (20:3 ω-6) are analogous.
Table 1 Three 20-carbon EFAs and the eicosanoid series derived from them
All prostanoids are substituted prostanoic acids. Cyberlipid Center's Prostenoid page[5] illustrates the parent compound and the rings associated with each series letter.
The IUPAC and the IUBMB use the equivalent term icosanoid.[5]
The arachidonic acid cascade in the Central Nervous System
The arachidonic acid cascade is arguably the most elaborate signaling system neurobiologists have to deal with.
The actions of eicosanoids within the brain are not as well characterized as they are in inflammation. Studies suggest that they act as second messengers within the neuron, possibly controlling presynaptic inhibition and the activation of protein kinase C. They also act as paracrine mediators, acting across synapses to nearby cells. The effects of these signals are not well understood. Daniele Piomelli has commented:
Neurons in the CNS are organized as interconnected groups of functionally related cells (e.g. in sensory systems). A diffusible factor released from a neuron into the interstitial fluid, and able to interact with membrane receptors on adjacent cells would be ideally used to "synchronize" the activity of an ensemble of interconnected neural cells. 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.[2]
Table 2.The arachidonic acid cascades act differently between the inflammatory response and the brain.
Arachidonic Acid Cascade
In inflammation
In the brain
Major effect on
Inflammation in tissue
Neuronal excitability
AA released from
White blood cells
Neurons
Triggers for AA release
Inflammatory stimuli
Neurotransmitters, neurohormones and neuromodulators
Intracellular effects on
DNA transcription of cytokines and other mediators of inflammation
↑ Cunnane SC (November 2003). "Problems with essential fatty acids: time for a new paradigm?". Progress in Lipid Research. 42 (6): 544–568. doi:10.1016/S0163-7827(03)00038-9. PMID14559071.
1 2 3 4 Piomelli, Daniele (2000). "Arachidonic Acid". Neuropsychopharmacology: The Fifth Generation of Progress. Archived from the original on 2006-07-15. Retrieved 2006-03-03.
↑ Freitas HR (2017-08-25). "Chlorella vulgaris as a Source of Essential Fatty Acids and Micronutrients: A Brief Commentary". The Open Plant Science Journal. 10 (1): 92–99. doi:10.2174/1874294701710010092 (inactive 1 November 2024). ISSN1874-2947.{{cite journal}}: CS1 maint: DOI inactive as of November 2024 (link)
↑ Freitas HR, Isaac AR, Malcher-Lopes R, Diaz BL, Trevenzoli IH, De Melo Reis RA (December 2018). "Polyunsaturated fatty acids and endocannabinoids in health and disease". Nutritional Neuroscience. 21 (10): 695–714. doi:10.1080/1028415X.2017.1347373. PMID28686542. S2CID40659630.
This page is based on this Wikipedia article Text is available under the CC BY-SA 4.0 license; additional terms may apply. Images, videos and audio are available under their respective licenses.
