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.
What is Glycoprotein ?:
Glycoproteins are proteins that contain oligosaccharide chains (glycans) covalently attached to polypeptide side-chains.
This process is known as glycosylation.
The carbohydrate is attached to the protein during the following modifications: Co-translational modification & Post-translational modification.
In proteins that have segments extending extracellularly, the extracellular segments are often glycosylated.
This presentation explains the fundamentals of Genetic Code, Protein synthesis mechanism and Antibiotics that inhibits at various stages of Translation.
Substrate level phosphorylation and it's mechanism || Biochemistry || B Pharmacy || Project || slideshare || biology || chemistry
*images use in this ppt is only for educational purpose
In this presentation, i tell about substrate level phosphorylation
Phosphorylation involves the transfer of phosphate
group from one compound to other.
➢ Substrate level phosphorylation is a direct
phosphorylation of ADP with a phosphatase group by
using the energy obtain from a coupled reaction.
➢ Occurs in cytoplasm ( glycolysis – due to aerobic and
anaerobic condition) and in mitochondrial matrix ( krebs
cycle – anaerobic condition)
Primary structure of protein
Secondary structure of protein
Tertiary structure of protein
Quaternary structure of protein
Methods to determine protein structure
Conclusion
References
METHODS TO DETERMINE PROTEIN STRUCTURE
Each protein has a unique sequence of amino acids.
The amino acids are held together in a protein by
covalent peptide bonds or linkages.
A peptide bond are formed when amino group of an
amino acid combines with the carboxyl group of another.
The conformation of polypeptide chain by twisting or folding is referred to as secondary structure.
Two types of secondary structures α-helix and β-sheet are mainly identified.
α-Helical structure was proposed by Pauling and Corey in 1951.
It occurs when the sequence of amino acids are linked by hydrogen bonds.
Each turn of α-helix contains 3.6 amino acids.
β-pleated sheets are composed of two or more segments of fully extended peptide chains.
β-Sheets may be arranged either in parallel or anti-parallel direction.
Many globular proteins contain combinations of α-helix and β-pleated sheet secondary structure, these patterns are called supersecondary structures also called motifs.
The three dimensional arrangement of protein structure is referred to as tertiary structure.
It is a compact structure with hydrophobic side chains held interior while the hydrophilic groups are on the surface.
This type of arrangement provide stability of the molecule.
Besides the H-bongs, disulfide bonds, ionic interactions, hydrophobic interactions also contribute to the tertiary structure.
General introduction about the autocoids like Function of Autocoids and it's classification and Introduction about the Ecosanoids, Histamine part having introduction, Properties, Mode of Action, Adverse Effect, Biosynthesis and metabolism all in a simple manner with related questions.
What is Glycoprotein ?:
Glycoproteins are proteins that contain oligosaccharide chains (glycans) covalently attached to polypeptide side-chains.
This process is known as glycosylation.
The carbohydrate is attached to the protein during the following modifications: Co-translational modification & Post-translational modification.
In proteins that have segments extending extracellularly, the extracellular segments are often glycosylated.
This presentation explains the fundamentals of Genetic Code, Protein synthesis mechanism and Antibiotics that inhibits at various stages of Translation.
Substrate level phosphorylation and it's mechanism || Biochemistry || B Pharmacy || Project || slideshare || biology || chemistry
*images use in this ppt is only for educational purpose
In this presentation, i tell about substrate level phosphorylation
Phosphorylation involves the transfer of phosphate
group from one compound to other.
➢ Substrate level phosphorylation is a direct
phosphorylation of ADP with a phosphatase group by
using the energy obtain from a coupled reaction.
➢ Occurs in cytoplasm ( glycolysis – due to aerobic and
anaerobic condition) and in mitochondrial matrix ( krebs
cycle – anaerobic condition)
Primary structure of protein
Secondary structure of protein
Tertiary structure of protein
Quaternary structure of protein
Methods to determine protein structure
Conclusion
References
METHODS TO DETERMINE PROTEIN STRUCTURE
Each protein has a unique sequence of amino acids.
The amino acids are held together in a protein by
covalent peptide bonds or linkages.
A peptide bond are formed when amino group of an
amino acid combines with the carboxyl group of another.
The conformation of polypeptide chain by twisting or folding is referred to as secondary structure.
Two types of secondary structures α-helix and β-sheet are mainly identified.
α-Helical structure was proposed by Pauling and Corey in 1951.
It occurs when the sequence of amino acids are linked by hydrogen bonds.
Each turn of α-helix contains 3.6 amino acids.
β-pleated sheets are composed of two or more segments of fully extended peptide chains.
β-Sheets may be arranged either in parallel or anti-parallel direction.
Many globular proteins contain combinations of α-helix and β-pleated sheet secondary structure, these patterns are called supersecondary structures also called motifs.
The three dimensional arrangement of protein structure is referred to as tertiary structure.
It is a compact structure with hydrophobic side chains held interior while the hydrophilic groups are on the surface.
This type of arrangement provide stability of the molecule.
Besides the H-bongs, disulfide bonds, ionic interactions, hydrophobic interactions also contribute to the tertiary structure.
General introduction about the autocoids like Function of Autocoids and it's classification and Introduction about the Ecosanoids, Histamine part having introduction, Properties, Mode of Action, Adverse Effect, Biosynthesis and metabolism all in a simple manner with related questions.
this file is all about eicosanoids including prostaglandins,prostacyclins and leukutriens with its mechanism of formation and inhibitors of LOX and COX pathways
Eicosanoids is the class of lipids derived from arachidonic acid. Eicosanoids play an important role in the growth and development, cellular signalling, drug response, platelet action and maintenance of body homeostasis.
Nutritional immunology is a fascinating but highly complex and conflicted subject area. With almost every nutrient we consume having the ability to affect our immune response in one way or another and the activation of the immune system dramatically increasing nutrient requirements, understanding the genetic, cellular and metabolic mechanisms that interact, control and conflict with the immune system and how to manipulate them to our advantage, is fundamental to optimal health.
We are thrilled to announce that we have linked up with Professor Phillip Calder, a world renowned and highly cited expert in nutritional immunology, with over 500 publications to his name. Professor Calder will be joining us as our guest speaker for our January Webinar to help us kick off what promises to be our most exciting year of clinical nutrition education yet.
In this detailed Q&A session Professor Calder will shed light on a whole host of fascinating topics from the latest research into nutrition immunology, his projects involving nutrigenomics, probiotics and omega-3s, the real science behind effective clinical omega-3 interventions, his thoughts on the best forms of lipid supplementation, and doing some serious nutrition science myth busting.
Sex linked describes the sex-specific patterns of inheritance and presentation when a gene mutation is present on a sex chromosome rather than a non-sex chromosome. In humans, these are termed X-linked recessive, X-linked dominant and Y-linked.
Connexins (Cx) (TC# 1.A.24), or gap junction proteins, are structurally related transmembrane proteins that assemble to form vertebrate gap junctions. An entirely different family of proteins, the innexins, form gap junctions in invertebrates.[1] Each gap junction is composed of two hemichannels, or connexons, which consist of homo- or heterohexameric arrays of connexins, and the connexon in one plasma membrane docks end-to-end with a connexon in the membrane of a closely opposed cell. The hemichannel is made of six connexin subunits, each of which consist of four transmembrane segments. Gap junctions are essential for many physiological processes, such as the coordinated depolarization of cardiac muscle, proper embryonic development, and the conducted response in microvasculature. For this reason, mutations in connexin-encoding genes can lead to functional and developmental abnormalities.
Cerebral circulation is the movement of blood through a network of cerebral arteries and veins supplying the brain. The rate of cerebral blood flow in an adult human is typically 750 milliliters per minute, or about 15% of cardiac output. Arteries deliver oxygenated blood, glucose and other nutrients to the brain. Veins carry "used or spent" blood back to the heart, to remove carbon dioxide, lactic acid, and other metabolic products.[1] Because the brain would quickly suffer damage from any stoppage in blood supply, the cerebral circulatory system has safeguards including autoregulation of the blood vessels. The failure of these safeguards may result in a stroke. The volume of blood in circulation is called the cerebral blood flow. Sudden intense accelerations change the gravitational forces perceived by bodies and can severely impair cerebral circulation and normal functions to the point of becoming serious life-threatening conditions.
Ecosystem is system formed by the interaction of a community of organisms with their physical environment.
Ecosystem can be natural or artificial.
Ecosystem has both abiotic and biotic components.
Ecosystem has primary, secondary and tertiary function.
Human social systems and ecosystems are complex adaptive systems
Ergonomics is the study of people in their working environment.
Cushing's syndrome is the pool of signs and symptoms due to extended exposure to glucocorticoids such as cortisol.
Signs and symptoms may include high blood pressure, abdominal obesity but with thin arms and legs, reddish stretch marks, a round red face, a fat lump between the shoulders, weak muscles, weak bones, acne, and fragile skin that heals poorly.
Women may have more hair and irregular menstruation. Occasionally there may be changes in mood, headaches, and a chronic feeling of tiredness.
Usual onset: 20 – 50 years
According to UNESCO Constructivism is learning theory which places the learner at the center of the educational process on the understanding that the learner actively constructs knowledge rather than passively receiving it.
According to Brader - Araje and Jones (2002), Constructivism can be defined as “the idea that development of understanding requires the learner to actively engage in meaning-making”.
Electroencephalography (EEG): an electrophysiological monitoring method to re...Habtemariam Mulugeta
Electroencephalography (EEG) is an electrophysiological monitoring method to record electrical activity of the brain.
It is typically noninvasive, with the electrodes placed along the scalp, although invasive electrodes are sometimes used, as in electrocorticography.
EEG measures voltage fluctuations resulting from ionic current within the neurons of the brain.
As Hall says; “To look at and listen to self is often too difficult without the help of a significant figure (nurturer) who has learned how to hold up a mirror and sounding board to invite the behaver to look and listen to himself. If he accepts the invitation, he will explore the concerns in his acts and as he listens to his exploration through the reflection of the nurse, he may uncover in sequence his difficulties, the problem area, his problem, and eventually the threat which is dictating his out-of-control behavior.”
The musculoskeletal system consists of the muscles, tendons, bones and cartilage together with the joints
The primary function of which is to produce skeletal movements
Pulmonary Thromboembolism - etilogy, types, medical- Surgical and nursing man...VarunMahajani
Disruption of blood supply to lung alveoli due to blockage of one or more pulmonary blood vessels is called as Pulmonary thromboembolism. In this presentation we will discuss its causes, types and its management in depth.
Explore natural remedies for syphilis treatment in Singapore. Discover alternative therapies, herbal remedies, and lifestyle changes that may complement conventional treatments. Learn about holistic approaches to managing syphilis symptoms and supporting overall health.
Prix Galien International 2024 Forum ProgramLevi Shapiro
June 20, 2024, Prix Galien International and Jerusalem Ethics Forum in ROME. Detailed agenda including panels:
- ADVANCES IN CARDIOLOGY: A NEW PARADIGM IS COMING
- WOMEN’S HEALTH: FERTILITY PRESERVATION
- WHAT’S NEW IN THE TREATMENT OF INFECTIOUS,
ONCOLOGICAL AND INFLAMMATORY SKIN DISEASES?
- ARTIFICIAL INTELLIGENCE AND ETHICS
- GENE THERAPY
- BEYOND BORDERS: GLOBAL INITIATIVES FOR DEMOCRATIZING LIFE SCIENCE TECHNOLOGIES AND PROMOTING ACCESS TO HEALTHCARE
- ETHICAL CHALLENGES IN LIFE SCIENCES
- Prix Galien International Awards Ceremony
New Directions in Targeted Therapeutic Approaches for Older Adults With Mantl...i3 Health
i3 Health is pleased to make the speaker slides from this activity available for use as a non-accredited self-study or teaching resource.
This slide deck presented by Dr. Kami Maddocks, Professor-Clinical in the Division of Hematology and
Associate Division Director for Ambulatory Operations
The Ohio State University Comprehensive Cancer Center, will provide insight into new directions in targeted therapeutic approaches for older adults with mantle cell lymphoma.
STATEMENT OF NEED
Mantle cell lymphoma (MCL) is a rare, aggressive B-cell non-Hodgkin lymphoma (NHL) accounting for 5% to 7% of all lymphomas. Its prognosis ranges from indolent disease that does not require treatment for years to very aggressive disease, which is associated with poor survival (Silkenstedt et al, 2021). Typically, MCL is diagnosed at advanced stage and in older patients who cannot tolerate intensive therapy (NCCN, 2022). Although recent advances have slightly increased remission rates, recurrence and relapse remain very common, leading to a median overall survival between 3 and 6 years (LLS, 2021). Though there are several effective options, progress is still needed towards establishing an accepted frontline approach for MCL (Castellino et al, 2022). Treatment selection and management of MCL are complicated by the heterogeneity of prognosis, advanced age and comorbidities of patients, and lack of an established standard approach for treatment, making it vital that clinicians be familiar with the latest research and advances in this area. In this activity chaired by Michael Wang, MD, Professor in the Department of Lymphoma & Myeloma at MD Anderson Cancer Center, expert faculty will discuss prognostic factors informing treatment, the promising results of recent trials in new therapeutic approaches, and the implications of treatment resistance in therapeutic selection for MCL.
Target Audience
Hematology/oncology fellows, attending faculty, and other health care professionals involved in the treatment of patients with mantle cell lymphoma (MCL).
Learning Objectives
1.) Identify clinical and biological prognostic factors that can guide treatment decision making for older adults with MCL
2.) Evaluate emerging data on targeted therapeutic approaches for treatment-naive and relapsed/refractory MCL and their applicability to older adults
3.) Assess mechanisms of resistance to targeted therapies for MCL and their implications for treatment selection
Title: Sense of Taste
Presenter: Dr. Faiza, Assistant Professor of Physiology
Qualifications:
MBBS (Best Graduate, AIMC Lahore)
FCPS Physiology
ICMT, CHPE, DHPE (STMU)
MPH (GC University, Faisalabad)
MBA (Virtual University of Pakistan)
Learning Objectives:
Describe the structure and function of taste buds.
Describe the relationship between the taste threshold and taste index of common substances.
Explain the chemical basis and signal transduction of taste perception for each type of primary taste sensation.
Recognize different abnormalities of taste perception and their causes.
Key Topics:
Significance of Taste Sensation:
Differentiation between pleasant and harmful food
Influence on behavior
Selection of food based on metabolic needs
Receptors of Taste:
Taste buds on the tongue
Influence of sense of smell, texture of food, and pain stimulation (e.g., by pepper)
Primary and Secondary Taste Sensations:
Primary taste sensations: Sweet, Sour, Salty, Bitter, Umami
Chemical basis and signal transduction mechanisms for each taste
Taste Threshold and Index:
Taste threshold values for Sweet (sucrose), Salty (NaCl), Sour (HCl), and Bitter (Quinine)
Taste index relationship: Inversely proportional to taste threshold
Taste Blindness:
Inability to taste certain substances, particularly thiourea compounds
Example: Phenylthiocarbamide
Structure and Function of Taste Buds:
Composition: Epithelial cells, Sustentacular/Supporting cells, Taste cells, Basal cells
Features: Taste pores, Taste hairs/microvilli, and Taste nerve fibers
Location of Taste Buds:
Found in papillae of the tongue (Fungiform, Circumvallate, Foliate)
Also present on the palate, tonsillar pillars, epiglottis, and proximal esophagus
Mechanism of Taste Stimulation:
Interaction of taste substances with receptors on microvilli
Signal transduction pathways for Umami, Sweet, Bitter, Sour, and Salty tastes
Taste Sensitivity and Adaptation:
Decrease in sensitivity with age
Rapid adaptation of taste sensation
Role of Saliva in Taste:
Dissolution of tastants to reach receptors
Washing away the stimulus
Taste Preferences and Aversions:
Mechanisms behind taste preference and aversion
Influence of receptors and neural pathways
Impact of Sensory Nerve Damage:
Degeneration of taste buds if the sensory nerve fiber is cut
Abnormalities of Taste Detection:
Conditions: Ageusia, Hypogeusia, Dysgeusia (parageusia)
Causes: Nerve damage, neurological disorders, infections, poor oral hygiene, adverse drug effects, deficiencies, aging, tobacco use, altered neurotransmitter levels
Neurotransmitters and Taste Threshold:
Effects of serotonin (5-HT) and norepinephrine (NE) on taste sensitivity
Supertasters:
25% of the population with heightened sensitivity to taste, especially bitterness
Increased number of fungiform papillae
Acute scrotum is a general term referring to an emergency condition affecting the contents or the wall of the scrotum.
There are a number of conditions that present acutely, predominantly with pain and/or swelling
A careful and detailed history and examination, and in some cases, investigations allow differentiation between these diagnoses. A prompt diagnosis is essential as the patient may require urgent surgical intervention
Testicular torsion refers to twisting of the spermatic cord, causing ischaemia of the testicle.
Testicular torsion results from inadequate fixation of the testis to the tunica vaginalis producing ischemia from reduced arterial inflow and venous outflow obstruction.
The prevalence of testicular torsion in adult patients hospitalized with acute scrotal pain is approximately 25 to 50 percent
TEST BANK for Operations Management, 14th Edition by William J. Stevenson, Ve...kevinkariuki227
TEST BANK for Operations Management, 14th Edition by William J. Stevenson, Verified Chapters 1 - 19, Complete Newest Version.pdf
TEST BANK for Operations Management, 14th Edition by William J. Stevenson, Verified Chapters 1 - 19, Complete Newest Version.pdf
Tom Selleck Health: A Comprehensive Look at the Iconic Actor’s Wellness Journeygreendigital
Tom Selleck, an enduring figure in Hollywood. has captivated audiences for decades with his rugged charm, iconic moustache. and memorable roles in television and film. From his breakout role as Thomas Magnum in Magnum P.I. to his current portrayal of Frank Reagan in Blue Bloods. Selleck's career has spanned over 50 years. But beyond his professional achievements. fans have often been curious about Tom Selleck Health. especially as he has aged in the public eye.
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Introduction
Many have been interested in Tom Selleck health. not only because of his enduring presence on screen but also because of the challenges. and lifestyle choices he has faced and made over the years. This article delves into the various aspects of Tom Selleck health. exploring his fitness regimen, diet, mental health. and the challenges he has encountered as he ages. We'll look at how he maintains his well-being. the health issues he has faced, and his approach to ageing .
Early Life and Career
Childhood and Athletic Beginnings
Tom Selleck was born on January 29, 1945, in Detroit, Michigan, and grew up in Sherman Oaks, California. From an early age, he was involved in sports, particularly basketball. which played a significant role in his physical development. His athletic pursuits continued into college. where he attended the University of Southern California (USC) on a basketball scholarship. This early involvement in sports laid a strong foundation for his physical health and disciplined lifestyle.
Transition to Acting
Selleck's transition from an athlete to an actor came with its physical demands. His first significant role in "Magnum P.I." required him to perform various stunts and maintain a fit appearance. This role, which he played from 1980 to 1988. necessitated a rigorous fitness routine to meet the show's demands. setting the stage for his long-term commitment to health and wellness.
Fitness Regimen
Workout Routine
Tom Selleck health and fitness regimen has evolved. adapting to his changing roles and age. During his "Magnum, P.I." days. Selleck's workouts were intense and focused on building and maintaining muscle mass. His routine included weightlifting, cardiovascular exercises. and specific training for the stunts he performed on the show.
Selleck adjusted his fitness routine as he aged to suit his body's needs. Today, his workouts focus on maintaining flexibility, strength, and cardiovascular health. He incorporates low-impact exercises such as swimming, walking, and light weightlifting. This balanced approach helps him stay fit without putting undue strain on his joints and muscles.
Importance of Flexibility and Mobility
In recent years, Selleck has emphasized the importance of flexibility and mobility in his fitness regimen. Understanding the natural decline in muscle mass and joint flexibility with age. he includes stretching and yoga in his routine. These practices help prevent injuries, improve posture, and maintain mobilit
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Couples presenting to the infertility clinic- Do they really have infertility...Sujoy Dasgupta
Dr Sujoy Dasgupta presented the study on "Couples presenting to the infertility clinic- Do they really have infertility? – The unexplored stories of non-consummation" in the 13th Congress of the Asia Pacific Initiative on Reproduction (ASPIRE 2024) at Manila on 24 May, 2024.
Evaluation of antidepressant activity of clitoris ternatea in animals
The Role of Eicosanoid in the Human Body.pptx
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
1
Habtemariam M.
2. “The Role of Eicosanoids in the Human Body”
Advanced Endocrinology
2 Habtemariam M.
3. 3
Outline
Objectives
Introduction
Abbreviation
Classification of Eicosanoids
Biosynthesis
Role of eicosanoids in Inflammation
Functions of Eicosanoids
Summary
Acknowledgement
References
3
Habtemariam M.
4. 4
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.
Habtemariam M.
4
5. 5
Introduction
5
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"
Habtemariam M.
Figure 1: Phospholipid
6. 6
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).
Habtemariam M.
6
7. 7
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
Habtemariam M.
7
8. 8
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).
Habtemariam M.
8
9. 9
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.
9
Habtemariam M.
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.
10. 10
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.
10
Habtemariam M.
11. 11
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
11
Habtemariam M.
Non-classic eicosanoids
13. 13
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.
Habtemariam M.
13
14. 14
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.
Habtemariam M.
14
15. 15
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.
Habtemariam M.
15
16. 16
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.
Habtemariam M.
16
17. 17
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.
Habtemariam M.
17
22. 22
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.
Habtemariam M.
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23. 23
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.
Habtemariam M.
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24. 24
Cont.
Pain:
The cytokines increase COX-2 activity.
This elevates levels of PGE2, sensitizing pain neurons.
Heat:
PGE2 is also a potent pyretic agent.
Habtemariam M.
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25. 25
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.
Habtemariam M.
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27. 27
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
Habtemariam M.
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28. 28
Cont.
In performing these roles, eicosanoids most often act as:
Autocrine Signaling
Paracrine Signaling
Eicosanoids may also act as Endocrine Agents
Habtemariam M.
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29. 29
Function, pharmacology, and clinical significance
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Table 1: summary of major Function, pharmacology, and clinical significance of Eicosanoids
32. 32
Summary
Habtemariam M.
32
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.
33. 33
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.
Habtemariam M.
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34. 34
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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Paper wasps, as shown on the cover, are representative of stinging insects in that their sting injects a venom containing a mixture of bioactive compounds. However, the venom of vespids (wasps, hornets) differs from that of other insects, including the apids (honey bees, bumble bees). Vespid venom includes histamine, which causes swelling, pain, and itching, as well as components which stimulate mast cells to release histamine and the eicosanoids prostaglandin D2 and leukotriene C4.
These bioactive lipids drive bronchoconstriction and edema, meaning that the wasp sting can be lethal if it occurs near the throat. Moreover, these mediators, with other components in wasp venom, contribute to the development of an allergic response. Sensitization to wasp venom can occur after a single sting, presenting the possibility of a potentially life-threatening anaphylactic reaction at some later date.
The venom of bees contrasts with that of the wasp in that it contains abundant melittin (Melittin is the main component (40–60% of the dry weight) and the major pain producing substance of honeybee (Apis mellifera) venom. Melittin is a basic peptide consisting of 26 amino acids.), It is a peptide which directly associates with cellular membranes and stimulates the action of cytosolic phospholipase A2 (cPLA2).
cPLA2 plays a critical role in the release of arachidonic acid for the generation of eicosanoids. Bee venom also includes a small (19 kDa) PLA2, unique to bees, which contributes to an allergic response. However, allergy to bee venom requires being stung frequently by bees and, as a result, is less common than sensitivity to wasp stings. Notably, individuals who are allergic to wasp venom are rarely allergic to bee venom. The roles for eicosanoids in insect stings are indicative of the diversity of actions for these bioactive lipids.
Eicosanoids is the collective term for straight-chain polyunsaturated fatty acids (PUFAs) of 20 carbon units in length that have been metabolized or otherwise converted to oxygen-containing products.
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.
a four-character abbreviation, composed of:
The number of their double bounds is indicated by their full and trivial names:
AA-derived hydroxy metabolites have four (i.e. 'tetra' or 'T') double bonds (e.g. 5-hydroxy-eicosa tetra enoic acid)
hydroperoxy (-OOH), hydroxy (-OH), or oxygen atom (=O) substituents link to a PUFA carbon by a single (-) or double (=) bond.
hydroperoxy (-OOH), hydroxy (-OH), or oxygen atom (=O) substituents link to a PUFA carbon by a single (-) or double (=) bond.
ω-6 Series eicosanoids derived from dihomo-gamma-linolenic acid. These metabolites are analogs of AA-derived eicosanoids but lack a double bound between carbons 5 and 6 and therefore have 1 less double bound than their arachidonic acid-derived analogs
Resolvins of the E series (RvE)
Other ω-3 series eicosapentaenoic acid-derived eicosanoids are analogs of ω-6 fatty acid-derived metabolites but contain a double bond between carbon 17 and 18 and therefore have one more double bound than their arachidonic acid-derived analogs. They include (HEPE is hydroxy-eicsapentaenoic acid)
Hydroxy are derived form mead acid
made by oxygenation of twenty-carbon fatty acids other than the classic eicosanoids.
Isofurans (256 Furan ring structure from AA), Isoprostanes (isoP) are non-enzymatically formed derivatives of PUFA studied as markers of oxidative stress; they include the following AA-derived isoP's which are named based on their structural similarities to PGs.
Furan is a heterocyclic organic compound, consisting of a five-membered aromatic ring with four carbon atoms and one oxygen atom. Chemical compounds containing such rings are also referred to as furans.
Endo-cannabi-noids: are certain glycerolipids or dopamine that are esterified to PUFA that activate cannabinoid receptors. - synaptic modulation and plasticity at a wide range of synapses throughout the central nervous system.
Combined an alcohol, combined with an acid, to form an ester.
Oxidative stress is a state that occurs when there is an excess of free radicals in the body's cells.
In this view, the opposing effects of ω-6 PUFA-derived and ω-3 PUFA-derived eicosanoids on key target cells underlie the detrimental and beneficial effects of ω-6 and ω-3 PUFA-rich diets on inflammation and allergy reactions, atherosclerosis, hypertension, cancer growth, and a host of other processes.
ω-6 PUFAs (AA and DGLA), ω-3 PUFA (eicosa-pentaenoic acid), and one ω-9 PUFA (mead acid). In general, the eicosanoids derived from AA promote inflammation, and those from EPA and from GLA (via DGLA) are less inflammatory, or inactive, or even anti-inflammatory and pro-resolving.
Most crop seeds and vegetable oils, including canola, soybean, corn, and sunflower oils, are major sources of n−6 FAs in the form of LA with low proportions of n−3 FAs (ALA)
Omega-3: Fish and other seafood (especially cold-water fatty fish, such as salmon, mackerel, tuna, herring, and sardines) Nuts and seeds (such as flaxseed, chia seeds, and walnuts)
Among the multiple subfamilies of eicosanoids, most prominently are PGs, TXs, LTs, LXs, RvEs, and EX.
The deleterious consequences associated with the consumption of ω-6 PUFA-rich diets reflects excessive production and activities of ω-6 PUFA-derived eicosanoids,
while the beneficial effects associated with the consumption of ω-3 PUFA-rich diets reflect the excessive production and activities of ω-3 PUFA-derived eicosanoids.
Eicosanoid biosynthesis begins when a cell is activated by mechanical trauma, ischemia, other physical perturbations, attack by pathogens, or stimuli made by nearby cells, tissues, or pathogens such as chemotactic factors, cytokines, growth factors, and even certain eicosanoids.
The activated cells then mobilize enzymes, termed phospholipase A2's (PLA2s), capable of releasing ω-6 and ω-3 fatty acids from membrane storage.
These fatty acids are bound in ester linkage to the SN2 position of membrane phospholipids; PLA2s act as esterases to release the fatty acid. There are several classes of PLA2s with type IV cytosolic PLA2s (cPLA2s) appearing to be responsible for releasing the fatty acids under many conditions of cell activation. The cPLA2s act specifically on phospholipids that contain AA, EPA or GPLA at their SN2 position. cPLA2 may also release the lysophospholipid that becomes platelet-activating factor
Eicosanoid biosynthesis begins when a cell is activated by mechanical trauma, ischemia, other physical perturbations, attack by pathogens, or stimuli made by nearby cells, tissues, or pathogens such as chemotactic factors, cytokines, growth factors, and even certain eicosanoids.
The activated cells then mobilize enzymes, termed phospholipase A2's (PLA2s), capable of releasing ω-6 and ω-3 fatty acids from membrane storage.
In the COX pathway, The key step is the enzymatic conversion of AA to the intermediate PGG2
Epoxy – eicosa trienoic acids (EETs)
Hydro – peroxy eicosa tetrae-noic acids (HPETEs)
Peroxidases are a group of enzymes that catalyze the oxidation of a substrate by hydrogen peroxide or an organic peroxide. Most peroxidases are ferric heme proteins
In the 5-LOX pathway,
Hydro – peroxy eicosa tetrae-noic acids (HPETEs)
venom of vespids (wasps, hornets) differs from that of other insects, including the apids (honey bees, bumble bees).
Vespid venom includes histamine, which causes swelling, pain, and itching, as well as components
which stimulate mast cells to release histamine and the eicosanoids prostaglandin D2 and leukotriene C4.
These bioactive lipids drive bronchoconstriction and edema, meaning that the wasp sting can be lethal if it occurs near the throat.
Moreover, these mediators, with other components in wasp venom, contribute to the development of an allergic response.
Sensitization to wasp venom can occur after a single sting, presenting the possibility of a potentially life-threatening anaphylactic reaction at some later date.
an insect's sting will trigger the classic inflammatory response
Since antiquity, the cardinal signs of inflammation have been known as: calor (warmth), dolor (pain), tumor (swelling), and rubor (redness).
The eicosanoids are involved with each of these signs.
Vespid venom includes histamine, which causes swelling, pain, and itching, as well as components
which stimulate mast cells to release histamine and the eicosanoids prostaglandin D2 and leukotriene C4.
These bioactive lipids drive bronchoconstriction and edema, meaning that the wasp sting can be lethal if it occurs near the throat.
Proinflammatory cytokines are produced predominantly by activated macrophages and are involved in the up-regulation of inflammatory reactions.Cytokines are small proteins that are crucial in controlling the growth and activity of other immune system cells and blood cells.
Aspirin and NSAIDS—drugs that block the COX pathways and stop prostanoid synthesis—limit fever or the heat of localized inflammation.
Selective COX-2 inhibitors currently used in valdecoxib
ω-6 PUFAs (AA and DGLA), ω-3 PUFA (eicosa-penta-enoic acid), and one ω-9 PUFA (mead acid). DGLA: PGA1, PGE1, and TXA1. AA: TXA2, PGA2, PGB2
In general, the eicosanoids derived from AA promote inflammation, and those from EPA and from GLA (via DGLA) are less inflammatory, or inactive, or even anti-inflammatory and pro-resolving.
So the presence of DGLA and EPA in tissues lowers the output of AA's eicosanoids.
ω-3 improves outcomes in hyper-tri-glyceride-mia, CVDs prevention, and hypertension, rheumatoid arthritis, and protection from ciclosporin toxicity in organ transplant patients. can ease symptoms in several psychiatric disorders.
decreased responsiveness, hallucinations, delusions, seizures, cortical blindness, and stroke-like episodes that mimic those clinical symptoms of mitochondrial encephalopathy.
Cyclosporine is used to prevent organ rejection in people who have received a liver, kidney, or heart transplant.
At each step, the ω-3 and ω-6 cascades compete for the enzymes. - cyclooxygenase and lipoxygenase enzymes
A gel or vaginal insert of prostaglandin is inserted into the vagina or a tablet is given by mouth. This is typically done overnight in the hospital to make the cervix "ripe" (soft, thinned out) for delivery. Administered alone, prostaglandin may induce labor or may be used before giving oxytocin
the use of vaginal PGE2 suppositories for induction of mid-trimester abortion or fetal demise in the third trimester is safe and effective.
Eicosanoids function in diverse physiological systems and pathological processes such as:
Besides the influence on eicosanoids, dietary PUFAs modulate immune response through three other molecular mechanisms.
They (a) alter membrane composition and function, including the composition of lipid rafts; (The CM of cells contain combinations of glycol-sphingo-lipids, cholesterol and protein receptors organised in glycolipoprotein lipid microdomains)
(b) change cytokine biosynthesis; and (cytokine: broad and loose category of small proteins (~5–25 kDa[1]) important in cell signaling)
(c) directly activate gene transcription. of these, the action on eicosanoids is the best explored.
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.
Table 1: summary of major Function, pharmacology, and clinical significance of Eicosanoids
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.