Omega Fatty Acids and Their Pathways

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Questions and Answers

What does phospholipase A2 (PLA2) primarily cleave from phospholipids?

Fatty acid and glycerol backbone

Free fatty acids only

Glycerol backbone only

Bond between lipid and glycerol backbone (correct)

What initiates the activation of phospholipase A2 (PLA2)?

Hydrolysis of PIP2 by phospholipase C (correct)

Release of free fatty acid

Phosphorylation by protein kinase A

Increase in intracellular Ca2+ concentration

Which omega fatty acid is a precursor to a variety of lipid mediators?

Arachidonic Acid (correct)

g-Linolenic Acid

Linoleic Acid

α-Linolenic Acid

What role do Ca2+ ions play in the activation of cytosolic PLA2 (cPLA2)?

They promote association of cPLA2 with the membrane Signup and view all the answers

Which of the following best describes the action of corticosteroids on phospholipase A2 (PLA2)?

They reduce total PLA2 activity and transcription of the PLA2 gene Signup and view all the answers

What is the role of phospholipase A2 in the synthesis pathway of lipid mediators?

It cleaves AA from membrane phospholipids. Signup and view all the answers

Which pathway is NOT involved in the synthesis of lipid mediators from Arachidonic Acid?

Phospholipase C pathway Signup and view all the answers

What is the common prostanoid intermediate generated by the action of cyclooxygenase (COX) on arachidonic acid?

PGH2 Signup and view all the answers

How do lipid mediators exert their effects in the body?

Through autocrine and paracrine signaling Signup and view all the answers

What effect do corticosteroids have on the gene for lipocortin?

Increase transcription Signup and view all the answers

Which omega-3 fatty acid is represented in the content provided?

DHA Signup and view all the answers

Which statement correctly describes the effect of phosphorylation by MAPK on cPLA2?

It induces an optimal conformation for activity Signup and view all the answers

Which process is primarily affected by cyclooxygenase due to arachidonic acid metabolism?

Production of prostanoids Signup and view all the answers

Lipid mediators are described as being very short-lived. What is a consequence of this characteristic?

They exert their effects only locally. Signup and view all the answers

What type of receptors do lipid mediators bind to for signaling?

G-protein-coupled receptors Signup and view all the answers

Which factor can influence the production of lipid mediators in tissues?

The presence of specific enzymatic machinery Signup and view all the answers

What role does PGE2 play in relation to pain sensation?

It reduces the threshold of nociceptor sensory neurons. Signup and view all the answers

Which prostanoid is primarily involved in promoting vasoconstriction and platelet aggregation?

TXA2 Signup and view all the answers

What is a significant physiological effect of PGI2?

Promoting vasodilation. Signup and view all the answers

Which isoform of cyclooxygenase (COX) is generally expressed in many tissues for housekeeping functions?

COX-1 Signup and view all the answers

What is the primary role of PGD2 in the context of inflammation?

Promote resolution of inflammation. Signup and view all the answers

In what aspect of reproductive health do PGF2a and PGE2 play important roles?

Labor and menstruation. Signup and view all the answers

How does TXA2 affect cardiovascular health?

It promotes vasoconstriction and increases platelet aggregation. Signup and view all the answers

What characterizes COX-2 in comparison to COX-1?

It is rapidly induced in response to inflammatory stimuli. Signup and view all the answers

What is one of the functions of Epi-LX?

Induce vasorelaxation Signup and view all the answers

Which fatty acid is essential and can be converted to EPA and DHA?

Alpha-linolenic acid Signup and view all the answers

What effect do the 3-series prostanoids and 5-series leukotrienes have on inflammation?

They are weakly inflammatory Signup and view all the answers

Which enzymes are involved in the conversion of EPA to E-series resolvins?

Acetyl-COX-2 and cytochrome p450 Signup and view all the answers

What are resolvins, protectins, and maresins classified as?

Lipid mediators Signup and view all the answers

Which pathway is most complex and still theoretical regarding DHA?

Pathway for D-series resolvins Signup and view all the answers

How does aspirin impact EPA during its conversion processes?

It enhances the conversion to E-series resolvins Signup and view all the answers

Which of the following is NOT a product of omega-3 fatty acid metabolism?

Cytokines Signup and view all the answers

What is the primary mechanism by which aspirin functions as a nonsteroidal anti-inflammatory drug (NSAID)?

Irreversible inhibition of COX-1 and modification of COX-2 activity Signup and view all the answers

Which of the following nonsteroidal anti-inflammatory drugs (NSAIDs) is commonly known for being a non-selective inhibitor?

Ibuprofen Signup and view all the answers

What is a possible risk associated with selective COX-2 inhibitors (coxibs)?

Increased risk of stroke and myocardial infarction Signup and view all the answers

Which enzyme is primarily associated with the production of leukotrienes?

Lipoxygenase-5 Signup and view all the answers

What is the role of the accessory protein FLAP in leukotriene synthesis?

Protein that activates lipoxygenase Signup and view all the answers

What common intermediate is produced during the synthesis of leukotrienes?

5-HPETE Signup and view all the answers

The discovery of how aspirin reduces prostaglandin and thromboxane synthesis was made by which scientist?

John Robert Vane Signup and view all the answers

Which statement is true concerning the effect of non-selective NSAIDs on cardiovascular events?

They can increase the risk of cardiovascular events. Signup and view all the answers

Study Notes

Omega Fatty Acids Overview

Omega-6 fatty acids include linoleic acid (found in soybean and sunflower oils) and arachidonic acid (found in meat).
Omega-3 fatty acids include alpha-linolenic acid (from flax and chia oils) and eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) (from fish and algae oil).

Membrane Incorporation

Arachidonic acid (AA), DHA, and EPA are integrated into membrane phospholipids across multitude cell types, affecting inflammation mediation.
Tissue-specific expression of enzymatic machinery determines lipid mediator production.

Arachidonic Acid (AA) Pathways

Overview of Lipid Mediators

AA is a precursor for various lipid mediators with pro- and anti-inflammatory effects; synthesized through activation of phospholipase A2 (PLA2).
PLA2 cleaves AA from membrane phospholipids, with two main pathways dependent on cyclooxygenase (COX) or lipoxygenase (LOX).

Phospholipase A2 Activation

PLA2 activation is a multi-step process initiated by extracellular signals activating phospholipase C (PLC).
PLC hydrolyzes PIP2 into secondary messengers, leading to calcium ion influx which activates protein kinase C (PKC) and subsequently cPLA2 for AA release.

Clinical Correlation

Corticosteroids target PLA2 to reduce AA availability, aiding in the management of inflammatory conditions by inhibiting PLA2 expression.

Cyclooxygenase Pathways: The Prostanoids

Prostanoids consist of prostaglandins, prostacyclins, and thromboxanes generated by COX enzymes through AA bisoxygenation and cyclization.
Physiological effects include vasodilation, edema, increased vascular permeability, and modulation of pain sensitivity.

COX Isoforms

COX-1 is regularly expressed in tissues for housekeeping functions, while COX-2 is rapidly induced by inflammation.
Nonsteroidal anti-inflammatory drugs (NSAIDs) such as ibuprofen and aspirin inhibit both COX isoforms, affecting pain and inflammation management.

Lipoxygenase Pathways

Leukotriene Synthesis

LOX enzymes, primarily LOX-5 expressed in leukocytes, convert AA into leukotrienes, mediating allergic responses and inflammation.
Eicosanoids such as lipoxins and epoxy-lipoxins also play roles in resolving inflammation by promoting vasorelaxation and inhibiting pro-inflammatory cytokines.

Omega-3 Fatty Acid Pathways

Conversion and Physiological Effects

Alpha-linolenic acid (ALA) can be converted to EPA and DHA, which serve as precursors for anti-inflammatory lipid mediators like resolvins, protectins, and maresins.
EPA can generate 3-series prostanoids and 5-series leukotrienes, functioning as competitive inhibitors to reduce inflammatory responses.

Metabolic Complexity

The pathways converting DHA to D-series resolvins, protectins, and maresins involve multiple LOX isoforms and complex synthesis processes.

Summary

Omega-6 and Omega-3 fatty acids play crucial roles in inflammatory processes through their conversion into various lipid mediators.
Understanding these pathways and their clinical implications is important for managing inflammatory diseases and conditions related to cardiovascular health.

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Description

Explore the essential omega fatty acids, focusing on omega-6 and omega-3 types, and their roles in cellular membranes and inflammation. Understand the pathways involved in arachidonic acid metabolism, including the enzymatic processes that lead to lipid mediator production and their implications for health.