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Questions and Answers
What does phospholipase A2 (PLA2) primarily cleave from phospholipids?
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)?
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?
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)?
What role do Ca2+ ions play in the activation of cytosolic PLA2 (cPLA2)?
Which of the following best describes the action of corticosteroids on phospholipase A2 (PLA2)?
Which of the following best describes the action of corticosteroids on phospholipase A2 (PLA2)?
What is the role of phospholipase A2 in the synthesis pathway of lipid mediators?
What is the role of phospholipase A2 in the synthesis pathway of lipid mediators?
Which pathway is NOT involved in the synthesis of lipid mediators from Arachidonic Acid?
Which pathway is NOT involved in the synthesis of lipid mediators from Arachidonic Acid?
What is the common prostanoid intermediate generated by the action of cyclooxygenase (COX) on arachidonic acid?
What is the common prostanoid intermediate generated by the action of cyclooxygenase (COX) on arachidonic acid?
How do lipid mediators exert their effects in the body?
How do lipid mediators exert their effects in the body?
What effect do corticosteroids have on the gene for lipocortin?
What effect do corticosteroids have on the gene for lipocortin?
Which omega-3 fatty acid is represented in the content provided?
Which omega-3 fatty acid is represented in the content provided?
Which statement correctly describes the effect of phosphorylation by MAPK on cPLA2?
Which statement correctly describes the effect of phosphorylation by MAPK on cPLA2?
Which process is primarily affected by cyclooxygenase due to arachidonic acid metabolism?
Which process is primarily affected by cyclooxygenase due to arachidonic acid metabolism?
Lipid mediators are described as being very short-lived. What is a consequence of this characteristic?
Lipid mediators are described as being very short-lived. What is a consequence of this characteristic?
What type of receptors do lipid mediators bind to for signaling?
What type of receptors do lipid mediators bind to for signaling?
Which factor can influence the production of lipid mediators in tissues?
Which factor can influence the production of lipid mediators in tissues?
What role does PGE2 play in relation to pain sensation?
What role does PGE2 play in relation to pain sensation?
Which prostanoid is primarily involved in promoting vasoconstriction and platelet aggregation?
Which prostanoid is primarily involved in promoting vasoconstriction and platelet aggregation?
What is a significant physiological effect of PGI2?
What is a significant physiological effect of PGI2?
Which isoform of cyclooxygenase (COX) is generally expressed in many tissues for housekeeping functions?
Which isoform of cyclooxygenase (COX) is generally expressed in many tissues for housekeeping functions?
What is the primary role of PGD2 in the context of inflammation?
What is the primary role of PGD2 in the context of inflammation?
In what aspect of reproductive health do PGF2a and PGE2 play important roles?
In what aspect of reproductive health do PGF2a and PGE2 play important roles?
How does TXA2 affect cardiovascular health?
How does TXA2 affect cardiovascular health?
What characterizes COX-2 in comparison to COX-1?
What characterizes COX-2 in comparison to COX-1?
What is one of the functions of Epi-LX?
What is one of the functions of Epi-LX?
Which fatty acid is essential and can be converted to EPA and DHA?
Which fatty acid is essential and can be converted to EPA and DHA?
What effect do the 3-series prostanoids and 5-series leukotrienes have on inflammation?
What effect do the 3-series prostanoids and 5-series leukotrienes have on inflammation?
Which enzymes are involved in the conversion of EPA to E-series resolvins?
Which enzymes are involved in the conversion of EPA to E-series resolvins?
What are resolvins, protectins, and maresins classified as?
What are resolvins, protectins, and maresins classified as?
Which pathway is most complex and still theoretical regarding DHA?
Which pathway is most complex and still theoretical regarding DHA?
How does aspirin impact EPA during its conversion processes?
How does aspirin impact EPA during its conversion processes?
Which of the following is NOT a product of omega-3 fatty acid metabolism?
Which of the following is NOT a product of omega-3 fatty acid metabolism?
What is the primary mechanism by which aspirin functions as a nonsteroidal anti-inflammatory drug (NSAID)?
What is the primary mechanism by which aspirin functions as a nonsteroidal anti-inflammatory drug (NSAID)?
Which of the following nonsteroidal anti-inflammatory drugs (NSAIDs) is commonly known for being a non-selective inhibitor?
Which of the following nonsteroidal anti-inflammatory drugs (NSAIDs) is commonly known for being a non-selective inhibitor?
What is a possible risk associated with selective COX-2 inhibitors (coxibs)?
What is a possible risk associated with selective COX-2 inhibitors (coxibs)?
Which enzyme is primarily associated with the production of leukotrienes?
Which enzyme is primarily associated with the production of leukotrienes?
What is the role of the accessory protein FLAP in leukotriene synthesis?
What is the role of the accessory protein FLAP in leukotriene synthesis?
What common intermediate is produced during the synthesis of leukotrienes?
What common intermediate is produced during the synthesis of leukotrienes?
The discovery of how aspirin reduces prostaglandin and thromboxane synthesis was made by which scientist?
The discovery of how aspirin reduces prostaglandin and thromboxane synthesis was made by which scientist?
Which statement is true concerning the effect of non-selective NSAIDs on cardiovascular events?
Which statement is true concerning the effect of non-selective NSAIDs on cardiovascular events?
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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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