Eicosanoids are signaling molecules made by the enzymatic or non-enzymatic oxidation of arachidonic acid or other polyunsaturated fatty acids (PUFAs) that are, similar to arachidonic acid, 20 carbon units in length. Eicosanoids are a sub-category of oxylipins, i.e. oxidized fatty acids of diverse carbon units in length, and are distinguished from other oxylipins by their overwhelming importance as cell signaling molecules. Eicosanoids function in diverse physiological systems and pathological processes such as: mounting or inhibiting inflammation, allergy, fever and other immune responses; regulating the abortion of pregnancy and normal childbirth; contributing to the perception of pain; regulating cell growth; controlling blood pressure; and modulating the regional flow of blood to tissues. In performing these roles, eicosanoids most often act as autocrine signaling agents to impact their cells of origin or as paracrine signaling agents to impact cells in the proximity of their cells of origin. Eicosanoids may also act as endocrine agents to control the function of distant cells.

1. “The Role of Eicosanoids in the Human Body”
College of Health Sciences
School of Medicine
Department of Medical Physiology
P.by: Habtemariam Mulugeta
ID No. GSR/2895/14
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Habtemariam M.

2. “The Role of Eicosanoids in the Human Body”
Advanced Endocrinology
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Outline
 Objectives
 Introduction
 Abbreviation
 Classification of Eicosanoids
 Biosynthesis
 Role of eicosanoids in Inflammation
 Functions of Eicosanoids
 Summary
 Acknowledgement
 References
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Objectives
 After completing this session, students should be able to:
Describe briefly about Eicosanoid.
Explain about the Biosynthesis of Eicosanoids.
Differentiate the Classification of Eicosanoids.
Appreciate the Role of Eicosanoid in Inflammation.
Familiarize with the Functions of Eicosanoids.
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Introduction
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 Eicosanoids are signaling molecules made by the enzymatic or non-enzymatic oxidation of PUFAs.
 The PUFA precursors to the eicosanoids include:
 Arachidonic acid (AA)
 Adrenic acid (AdA)
 Eicosapentaenoic acid (EPA)
 Dihomo-gamma-linolenic acid (DGLA)
 Mead acid
 Eicosanoid - eicosa- Greek for "twenty"
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Figure 1: Phospholipid

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Abbreviation
 Eicosanoid is denoted by:
 Two-letter abbreviation (LT, EX or PG)
 One A-B-C sequence-letter
 Subscript number following the designated eicosanoid's trivial name indicates the
number of its double bonds.
 Examples: EPA derived:
 Prostanoids have 3 double bonds (e.g. PGG3 or PGG3)
 Leukotrienes have 5 double bonds (e.g. LTB5 or LTB5).
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Cont.
 Hp or HP for a hydroperoxy residue, H for a hydroxy residue, oxo- for an oxo residue
 Examples:
 5-hydroperooxy-eicosatraenoic acid: 5-HpETE or 5-HPETE
 5-hydroxy-eicosatetraenoic acid: 5-HETE
 5-oxo-eicosatetraenioic acid: 5-oxo-ETE or 5-oxoETE
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Cont.
 The number of their double bounds is indicated by their full and trivial names
 Example:
 AA-derived hydroxy metabolites have four (i.e. 'tetra' or 'T') double bonds
(e.g. 5-hydroxy-eicosatetraenoic acid = 5-HETE);
 EPA-derived hydroxy metabolites have five ('penta' or 'P') double bonds
(e.g. 5-hydroxy-eicosapentaenoic acid = 5-HEPE);
 DGLA-derived hydroxy metabolites have three ('tri' or 'Tr') double bonds
(e.g. 5-hydroxy-eicosatrienoic acid = 5-HETrE).
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Classification of Eicosanoids
 ω-6 Series eicosanoids derived from AA:
o HETE: 5-HETE, 12-HETE, 15-HETE, 20-HETE,
o LT: LTA4, LTB4, LTC4, LTD4, and LTE4.
o EX: EXA4, EXC4, EXD4, and EXE4.
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 CLASSIC EICOSANOIDS
o Prostanoids consisting of several different types:
 PG: PGG2, PGH2, PGE2, PGD2, PGF2alpha, PGA2,
PGB2
 Prostacyclins: PGI2 (see prostacyclin).
 TX: TXA2 and TXB2.
 Cyclopentenone prostaglandins: PGA1, PGA2.

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Cont.
 ω-6 Series eicosanoids derived from DGLA: PGA1, PGE1, and
TXA1.
 ω-3 Series eicosanoids:
o RvE: RvE1, 18S-RvE1, RvE2, and RvE3.
o HEPE: 5-HEPE, 12-HEPE, 15-HEPE, and 20-HETE
 ω-9 Series eicosanoids: 5-HETrE.
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Cont.
 oxo-ETE:
 5-oxo-ETE, 12-oxo-ETE, and 15-oxo-ETE,
 Hepoxilins (Hx):
 HxA3 and HxB3
 Lipoxins (Lx):
 LxA4 and LxB4
 Epi-lipoxins (epi-Lx):
 15-epi-LxA4 (AT-LxA4) and 15-epi-LxB4 (AT-LxB4
 Epoxyeicosatrienoic acids (EET):
 5,6-EET, 8,9-EET, 11,12-EET, and 14,15-EET
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 Non-classic eicosanoids

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Cont.
 Epoxyeicosatetraenoic acid (EEQ):
 5,6-EEQ, 8,9-EEQ, 11,12-EEQ, 14,15-EEQ,
 Endocannabinoids:
 Arachidonoylethanolamine
 2-Arachidonoylglycerol.
 Isofurans.
 Isoprostanes (isoP):
 D2-isoPs, E2-isoPs, A2-isoPs, and J2-isoPs;
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Cont.
 Mammals, including Humans, are unable to convert ω-6 into ω-3 PUFA.
 The ω-6 & ω-3 PUFA series of metabolites have almost opposing
physiological & pathological activities.
 Tissue levels of the ω-6 and ω-3 PUFAs and their corresponding eicosanoid
metabolites link directly to the amount of dietary ω-6 versus ω-3 PUFAs
consumed.
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Biosynthesis
 Eicosanoids typically are not stored within cells but rather synthesized as required.
 They derive from the fatty acids that make up the cell membrane and nuclear membrane.
 These fatty acids must be released from their membrane sites
 Then metabolized initially to products
 Those products further metabolized through various pathways
 make the large array of products we recognize as bioactive eicosanoids.
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Cont.
 AA is a PUFA that constitutes the phospholipid domain of most cell membranes (CM).
 It is liberated from the CM by cytoplasmic phospholipase A2 (PLA2).
 Free AA can be metabolized to eicosanoids through three major pathways:
1. The cyclooxygenase (COX),
2. The lipoxygenase (LOX),
3. The cytochrome P450 monooxygenase pathways.
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Cont.
 Enzymatic conversion of AA to the intermediate PGG2, which is then reduced to
an intermediate PGH2 by the peroxidase activity of COX.
 PGH2 is sequentially metabolized to prostanoids, including PGs and TXs by
specific PGs & TX synthases.
 LOXs convert AA into biologically active metabolites such as LTs and HETEs;
 P450 metabolizes AA into epoxyeicosatrienoic acids (EETs), HETEs and HPETEs.
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Cont.
 AA is converted to an intermediary 5-HPETE, which is further metabolized to
form the unstable LTA4.
 LTA4 is subsequently converted to 5-HETE, LTB4, LTC4, LTD4 and LTE4.
 Each of the PGs and LTs exerts its biological effects by binding to its cognate
G protein-coupled receptor.
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Cont.
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Figure 2: Biosynthesis of Eicosanoids from AA

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Cont.
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Figure 3: COX
Figure 4: LOX

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Cont.
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Figure 1: Overview of
Eicosanoid Synthesis
Pathways.

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Role of eicosanoids in Inflammation
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Figure 2: Wasps

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Cont.
 Redness:
 Short acting vasoconstrictors - TXA2 - are released quickly after the injury.
 The site may momentarily turn pale.
 Then TXA2 mediates the release of the vasodilators PGE2 and LTB4.
 The blood vessels engorge and the injury reddens.
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Cont.
 Swelling:
 LTB4 makes the blood vessels more permeable.
 Plasma leaks out into the connective tissues, and they swell.
 The process also loses pro-inflammatory cytokines.
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Cont.
 Pain:
 The cytokines increase COX-2 activity.
 This elevates levels of PGE2, sensitizing pain neurons.
 Heat:
 PGE2 is also a potent pyretic agent.
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Cont.
 Dietary ω-3 and GLA counter the inflammatory effects of AA's eicosanoids in three ways,
along the eicosanoid pathways:
• Displacement: Dietary ω-3 decreases tissue concentrations of AA, so there is less to form
ω-6 eicosanoids.
• Competitive inhibition: DGLA and EPA compete with AA for access to the
cyclooxygenase and lipoxygenase enzymes.
• Counteraction: Some DGLA and EPA derived eicosanoids counteract their AA derived
counterparts.
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Cont.
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Figure 2: Essential fatty acid
production and metabolism to form
eicosanoids

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Functions of Eicosanoids
 Mounting or Inhibiting Inflammation, Allergy, Fever & Other Immune Responses;
 Regulating the Abortion of Pregnancy & Normal Childbirth;
 Contributing to the Perception of Pain;
 Regulating Cell Growth;
 Controlling Blood Pressure;
 Modulating the Regional Flow of Blood to Tissues
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Cont.
 In performing these roles, eicosanoids most often act as:
 Autocrine Signaling
 Paracrine Signaling
 Eicosanoids may also act as Endocrine Agents
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Function, pharmacology, and clinical significance
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Table 1: summary of major Function, pharmacology, and clinical significance of Eicosanoids

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Cont.
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Cont.
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Summary
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Eicosanoids are signaling molecules made by the enzymatic or non-
enzymatic oxidation of arachidonic acid or other polyunsaturated fatty acids.
Eicosanoids are a sub-category of oxylipins.
Eicosanoids function in diverse physiological systems and pathological processes such as:
mounting or inhibiting inflammation, allergy, fever and other immune responses;
In performing these roles, eicosanoids most often act as autocrine signaling, paracrine
signaling or endocrine agents to control the function of distant cells.

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Acknowledgement
 Firstly, I would like Thanks Our Lord and Savior Jesus Christ Son of the True Living God,
with his Most Holy Mother Theotokos and all the Saints.
 Next my deepest gratitude goes to my instructor Dr. Dresbachew who gave me this chance
to prepare and present on “The Role of Eicosanoids in the Human Body.”
 Finally, I would like to thank my family & friends for their support of my works.
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References
 University of Kansas Medical Center (2004). "Eicosanoids and Inflammation" (PDF).
Archived from the original (PDF) on 2005-05-16. Retrieved 2007-01-05.
 Ivanov, I; Kuhn, H; Heydeck, D (2015). "Structural and functional biology of arachidonic
acid 15-lipoxygenase-1 (ALOX15)". Gene. 573 (1): 1–32.
 Fritsche, Kevin (August 2006). "Fatty Acids as Modulators of the Immune
Response". Annual Review of Nutrition. 26: 45–
73. doi:10.1146/annurev.nutr.25.050304.092610. PMID 16848700.
 Serhan CN, Chiang N (2013). "Resolution phase lipid mediators of inflammation: agonists
of resolution". Current Opinion in Pharmacology. 13 (4): 632–40.
 Capra V, Rovati GE, Mangano P, Buccellati C, Murphy RC, Sala A (2015). "Transcellular
biosynthesis of eicosanoid lipid mediators". Biochimica et Biophysica Acta (BBA) -
Molecular and Cell Biology of Lipids. 1851 (4): 377–82.
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