B59: Eicosanoids

Eicosanoids are not stored, meaning they are synthesized and released on demand. They have a short half-life, which means they are rapidly metabolized and cleared from the body. This short half-life allows for precise control and regulation of their effects on various physiological processes.

Thromboxane is a hormone that promotes platelet aggregation, which means it causes the platelets to clump together and form blood clots. On the other hand, prostacyclin inhibits platelet aggregation, meaning it prevents the platelets from sticking together and forming clots.

COX-1 is involved in normal physiological functions of prostaglandins (PG) and thromboxanes (TX), which include gastric protection and limiting acid secretion, maintenance of renal blood flow, vascular homeostasis, and hemostasis. COX-1 is constitutively expressed in various tissues and is responsible for the production of PGs and TXs that play a role in these physiological processes. COX-2, on the other hand, is primarily induced during inflammation and is responsible for the production of PGs that mediate pain, fever, and inflammation.

Eicosanoids act locally rather than after transport in the blood to distant sites. This means that they are produced and exert their effects in the immediate vicinity of their site of production, instead of being transported through the bloodstream to act on distant target cells or tissues. This is in contrast to true hormones like insulin, which are produced in one location and then transported through the blood to act on target cells in various parts of the body.

Eicosanoids are synthesized from a fatty acid with 20 carbons. This information can be found on page 213 of the textbook and in the Trotz Lectures on pages 53-59, specifically on page 58.

The correct answer is "linear" because the passage states that the pathway includes lipoxygenases, which are enzymes that catalyze the oxygenation of polyunsaturated fatty acids in a linear manner. This linear pathway leads to the production of leukotrienes, HETE, and lipoxins.

TXA2, also known as thromboxane A2, is mainly produced by platelets and has several effects on the body. It stimulates platelet aggregation, which is the process of platelets clumping together to form a blood clot. TXA2 also causes vasoconstriction, which narrows the blood vessels and increases blood pressure. Additionally, it causes bronchoconstriction, which leads to the narrowing of the airways in the lungs. These effects of TXA2 play important roles in hemostasis, the regulation of blood flow, and the inflammatory response.

COX-1 is constitutive, meaning it is constantly present and active in the body. On the other hand, COX-2 is inducible, which means it is only produced in response to certain stimuli or conditions. This difference in their regulation and expression levels is important in understanding their roles and functions in various physiological processes.

Eicosanoids differ from true hormones because they are produced in very small amounts in almost all tissues, rather than in specialized glands. This means that eicosanoids have a more widespread and localized effect in the body, compared to hormones which are typically produced in larger amounts by specific glands and have a more systemic effect.

Aspirin is known to irreversibly inhibit the enzyme COX (cyclooxygenase). This means that once aspirin binds to the active site of COX, it forms a covalent bond with the enzyme, permanently inactivating it. This irreversible inhibition is a key characteristic of aspirin's mechanism of action and is responsible for its long-lasting effects on platelet aggregation and inflammation.

The correct answer is "cyclic" because the pathway mentioned in the question involves fatty acid cyclooxygenase, which is an enzyme that catalyzes the conversion of arachidonic acid into cyclic endoperoxides. These cyclic endoperoxides can then be further metabolized to produce prostaglandins or thromboxane. Therefore, the pathway is cyclic in nature.

PGI2, also known as prostacyclin, is produced by vascular endothelial cells. It inhibits platelet aggregation, meaning it prevents platelets from clumping together and forming blood clots. Additionally, PGI2 has vasodilatory effects, meaning it relaxes and widens blood vessels, leading to increased blood flow.

LTE4 is an inflammatory mediator that is a component of SRS-A (slow-reacting substance of anaphylaxis). It, along with LTC4 and LTD4, leads to severe bronchoconstriction and lung edema. LTE4 is formed from the metabolism of LTD4 and plays a crucial role in the pathophysiology of asthma and other allergic respiratory diseases. Its presence contributes to the narrowing of airways and the accumulation of fluid in the lungs, resulting in the symptoms associated with severe bronchoconstriction and lung edema.

Prostaglandins, thromboxanes, and leukotrienes are all types of eicosanoids. Eicosanoids are signaling molecules that are derived from fatty acids and play important roles in inflammation, immune response, and various other physiological processes. Prostaglandins and thromboxanes are involved in regulating inflammation and blood clotting, while leukotrienes are primarily associated with allergic and inflammatory responses. Therefore, leukotrienes are the correct answer to complete the list of eicosanoids.

The correct answer is "arachidonic acid" because according to the information provided in the Trotz Lectures, EPA (eicosapentaenoic acid) can be released and used for eicosanoid synthesis. This implies that EPA is an alternative to arachidonic acid in the process of eicosanoid synthesis.

LTB (Lipoteichoic acid) increases vascular permeability and acts as a chemo-attractant for neutrophils. This information is stated in Trotz Lectures 53-59 on page 66.

PGF2-alpha is a prostaglandin that acts as a vasoconstrictor, causing the constriction of blood vessels. It also contracts smooth muscle, which can lead to various effects in different organs and tissues. Additionally, PGF2-alpha is known to induce bronchoconstriction, causing the narrowing of the airways in the lungs. These actions make PGF2-alpha a potent regulator of vascular tone, smooth muscle contraction, and bronchial constriction.

PGE2 and PGF2-alpha have partially opposing effects. This means that they have different effects on certain processes or functions in the body. While the specific effects are not mentioned in the given information, it can be inferred that PGE2 and pge2 are the substances being referred to as they are mentioned in the same context.

LTs (leukotrienes) are lipid mediators that are produced by various cells, including mast cells and leukocytes, during an inflammatory response. They are known to increase vascular permeability, which allows immune cells to enter the site of inflammation. Additionally, LTs can also cause severe bronchoconstriction, leading to symptoms such as wheezing and difficulty breathing. Therefore, the correct answer is LTC, LTD, LTE, as these leukotrienes both increase vascular permeability and cause bronchoconstriction.

PGH2 is an intermediate of prostaglandin and thromboxane synthesis.

Arachidonic acid is a type of fatty acid that is found in the body and is involved in the production of various substances, including prostaglandins. Prostaglandin H2 (PGH2) is a precursor molecule that is derived from arachidonic acid. Therefore, the correct answer is arachidonic acid because it is the compound that yields PGH2.

Prostaglandins and thromboxanes are molecules that play important roles in various physiological processes. They often have opposing actions, meaning they counteract each other's effects. Both prostaglandins and thromboxanes are necessary for maintaining normal cell functions in the body. This information is mentioned in Trotz Lectures 53-59 on page 58.

Continuous severe inhibition of COX-1 at high aspirin doses can lead to stomach ulcers and kidney damage. COX-1 is an enzyme involved in the production of prostaglandins, which are important for maintaining the integrity of the stomach lining and regulating kidney function. Inhibition of COX-1 reduces the production of these protective prostaglandins, leading to increased risk of stomach ulcers and kidney damage.

PGI2, also known as prostacyclin, and TXA2 have opposing effects. Prostacyclin is a vasodilator and inhibitor of platelet aggregation, while TXA2 is a vasoconstrictor and promoter of platelet aggregation. These two substances play important roles in regulating blood flow and clotting.

PGE2 can lead to vasodilation and relaxation of smooth muscle through the activation of cAMP. This is supported by the information given in Trotz Lectures 53-59 on page 64.

Aspirin inhibits COX by acetylating a serine residue in the active site. This acetylation prevents the enzyme from functioning properly, thereby reducing the production of prostaglandins and other inflammatory compounds. By targeting this specific residue, aspirin effectively reduces pain, inflammation, and fever.

Prostaglandins have a 5-membered ring, while thromboxane has a 6-membered ring.

Leukotrienes are known to primarily function as inflammatory mediators, along with lipoxins and HETE. This information is mentioned in the Trotz Lectures, specifically on page 58, between lecture numbers 53-59. Therefore, the correct answer for this question is leukotrienes.

5-HPETE is an intermediate of leukotriene synthesis. Leukotrienes are a group of inflammatory molecules that are involved in various physiological processes, including asthma and allergic reactions. 5-HPETE is formed from the metabolism of arachidonic acid and serves as a precursor for the synthesis of leukotrienes. Therefore, it can be concluded that 5-HPETE is an intermediate in the synthesis of leukotrienes.

LTA is used in mast cells and eosinophils to form LTC by addition of the tripeptide GSH.

PGH synthase, also known as prostaglandin endoperoxide synthase, possesses two catalytic activities: fatty acid cyclooxygenase and peroxidase. The given answer, peroxidase, is the missing catalytic activity of PGH synthase. This enzyme is responsible for the conversion of fatty acids into prostaglandin endoperoxides and also plays a role in the production of other bioactive molecules. The information regarding the two catalytic activities of PGH synthase can be found on page 213 of the mentioned source and in the Trotz Lectures on pages 53-59, specifically on page 61.

Corticosteroids, such as cortisol, inhibit phospholipase A2, which is involved in the release of arachidonic acid. This inhibition prevents the synthesis of eicosanoids, as arachidonic acid is the substrate required for their production. Therefore, corticosteroids indirectly inhibit the synthesis of eicosanoids by inhibiting the enzyme responsible for releasing the necessary substrate.

LTA (lipoteichoic acid) is an intermediate molecule that undergoes a change to LTB (lipoteichoic acid binding protein) in neutrophils and monocytes. This change is likely a part of the immune response, as LTB is involved in the binding and activation of immune cells.

The cysteinyl-leukotrienes are known to be components of the slow-reacting substance of anaphylaxis (SRS-A). They are involved in the immune response and inflammation that occurs during anaphylaxis, a severe allergic reaction.

Asthma treatment can involve inhibiting the synthesis of leukotrienes or blocking leukotriene receptors. Leukotrienes are inflammatory molecules that play a role in the pathogenesis of asthma. By inhibiting their synthesis or blocking their receptors, the inflammatory response in the airways can be reduced, leading to improved asthma control. This approach is commonly used in the management of asthma and can be effective in reducing symptoms and preventing exacerbations.

Prostaglandins, in general, can induce labor. This information is mentioned in the Trotz Lectures on pages 53-59, specifically on page 64. Prostaglandins are a group of hormones that play a role in various physiological processes, including labor and childbirth. They can help to ripen the cervix, stimulate contractions, and initiate the labor process. Therefore, prostaglandins can be used as a medical intervention to induce labor when necessary.