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Organic Chemistry
Table of Contents
Unit 27 Overview: Biomolecules
27.1 Waxes, Fats, and Oils
27.2 Soap
27.3 Phospholipids
27.4 Prostaglandins and Other Eicosanoids
27.5 Terpenoids
27.6 Steroids
27.7 Biosynthesis of Steroids

🥼organic chemistry review

27.4 Prostaglandins and Other Eicosanoids

Citation:

Prostaglandins and eicosanoids are lipid molecules that act as local hormones in our bodies. They're involved in many processes, from inflammation to blood clotting, and are made from a fatty acid called arachidonic acid.

These compounds are produced by two main pathways: cyclooxygenase (COX) and lipoxygenase (LOX). Understanding how they're made and work helps us grasp their role in health and disease, as well as how certain medications affect our bodies.

Prostaglandins and Other Eicosanoids

Structure and effects of prostaglandins

  • Prostaglandins are a class of eicosanoids derived from arachidonic acid
    • Contain a cyclopentane ring and two side chains
    • Designated by the letters A through I, depending on the structure of the cyclopentane ring (PGE2, PGF2α)
  • Prostaglandins act as local hormones, regulating various physiological processes
    • Inflammatory response
      • Some prostaglandins promote inflammation (PGE2, PGF2α)
      • Others have anti-inflammatory effects (PGE1)
    • Smooth muscle contraction and relaxation
      • PGE2 and PGI2 cause vasodilation and bronchodilation
      • PGF2α causes vasoconstriction and bronchoconstriction
    • Platelet aggregation
      • TXA2 promotes platelet aggregation
      • PGI2 inhibits platelet aggregation
    • Gastrointestinal protection
      • PGE2 and PGI2 protect the stomach lining from acid and ulcers
    • Renal function
      • PGE2 and PGI2 regulate renal blood flow and electrolyte balance
    • Reproductive processes
      • PGE2 and PGF2α are involved in ovulation, menstruation, and labor induction

Biosynthesis of eicosanoids

  • Arachidonic acid is released from cell membrane phospholipids by phospholipase A2
    • Arachidonic acid is derived from omega-6 fatty acids in the diet
  • Cyclooxygenase (COX) pathway
    1. Arachidonic acid is converted to prostaglandin H2 (PGH2) by COX enzymes
      • Two isoforms: COX-1 (constitutive) and COX-2 (inducible)
    2. PGH2 is further metabolized by specific synthases to form various prostaglandins and thromboxanes
      • Prostaglandin E2 (PGE2) by PGE synthase
      • Prostaglandin F2α (PGF2α) by PGF synthase
      • Prostaglandin I2 (PGI2 or prostacyclin) by prostacyclin synthase
      • Thromboxane A2 (TXA2) by thromboxane synthase
  • Lipoxygenase (LOX) pathway
    1. Arachidonic acid is converted to hydroperoxyeicosatetraenoic acids (HPETEs) by LOX enzymes
      • 5-LOX, 12-LOX, and 15-LOX
    2. HPETEs are further metabolized to form leukotrienes and lipoxins
      • Leukotriene A4 (LTA4) is converted to LTB4, LTC4, LTD4, and LTE4
      • Lipoxins (LXA4 and LXB4) are formed from 15-HPETE

COX-1 vs COX-2 in prostaglandin production

  • COX-1 (cyclooxygenase-1)
    • Constitutively expressed in most tissues
    • Involved in the production of prostaglandins for homeostatic functions
      • Gastrointestinal protection
      • Platelet aggregation
      • Renal function
  • COX-2 (cyclooxygenase-2)
    • Inducible enzyme, expressed in response to inflammatory stimuli
    • Primarily involved in the production of prostaglandins during inflammation
      • Mediates pain, fever, and swelling
  • Non-steroidal anti-inflammatory drugs (NSAIDs) inhibit COX enzymes
    • Non-selective NSAIDs (aspirin, ibuprofen) inhibit both COX-1 and COX-2
      • Effective in reducing inflammation but may cause gastrointestinal side effects due to COX-1 inhibition
    • Selective COX-2 inhibitors (celecoxib) specifically target COX-2
      • Reduce inflammation with fewer gastrointestinal side effects
      • May increase the risk of cardiovascular events

Eicosanoids as Lipid Mediators in Cell Signaling

  • Eicosanoids function as lipid mediators in various cellular processes
  • They play crucial roles in cell signaling pathways related to inflammation and immune responses
  • Eicosanoids act through specific G protein-coupled receptors to initiate intracellular signaling cascades
  • The biosynthesis and release of eicosanoids are tightly regulated to maintain physiological balance
  • Dysregulation of eicosanoid signaling can contribute to various pathological conditions

Key Terms to Review (36)

Eicosanoids: Eicosanoids are a group of bioactive lipids derived from arachidonic acid or other polyunsaturated fatty acids that play critical roles in inflammation, immunity, and as messengers in the central nervous system. They include prostaglandins, thromboxanes, leukotrienes, and others, each involved in various physiological and pathological processes.
Eicosanoid: Eicosanoids are a group of bioactive lipid-based molecules derived from the fatty acid arachidonic acid, playing crucial roles in inflammation, immunity, and other important cellular processes. They include prostaglandins, thromboxanes, and leukotrienes, each serving various regulatory functions in the body.
Prostaglandins: Prostaglandins are a group of lipid compounds derived from arachidonic acid that act as local hormones, regulating various physiological and pathological processes in the body. They are involved in the regulation of inflammation, pain, and other important functions.
PGF2α: PGF2α, or Prostaglandin F2α, is a bioactive lipid compound that plays a crucial role in various physiological processes, including the regulation of the menstrual cycle, uterine contractions, and inflammation. It is a member of the prostaglandin family, a group of eicosanoids derived from arachidonic acid.
PGE1: PGE1, or Prostaglandin E1, is a naturally occurring lipid compound that belongs to the class of eicosanoids. It is a key player in various physiological processes and is particularly relevant in the context of cis-trans isomerism in cycloalkanes and the broader field of prostaglandins and other eicosanoids.
Arachidonic Acid: Arachidonic acid is a polyunsaturated fatty acid that plays a crucial role in various biological processes, particularly in the context of prostaglandin synthesis and the body's inflammatory response. It is a key precursor for the production of eicosanoids, a group of signaling molecules that regulate a wide range of physiological functions.
PGH2: PGH2, or Prostaglandin H2, is a key intermediate in the biosynthesis of various prostaglandins and other eicosanoids, which are important signaling molecules involved in a wide range of physiological and pathological processes in the body.
Cyclooxygenase: Cyclooxygenase (COX) is an enzyme that catalyzes the first step in the biosynthesis of prostaglandins, prostacyclin, and thromboxanes - a group of lipid-based signaling molecules known as eicosanoids. This enzyme plays a crucial role in the body's inflammatory response and pain perception.
Leukotrienes: Leukotrienes are a class of inflammatory lipid mediators derived from arachidonic acid, a polyunsaturated fatty acid. They play a crucial role in the body's inflammatory response and are associated with various pathological conditions.
Lipid Mediators: Lipid mediators are a class of bioactive lipid molecules that play crucial roles in various physiological and pathological processes within the body. These lipid-derived signaling molecules are involved in the regulation of inflammation, immune responses, and other important cellular functions.
Omega-6 Fatty Acids: Omega-6 fatty acids are a class of polyunsaturated fatty acids that are essential for human health. They are involved in the production of eicosanoids, which are signaling molecules that play crucial roles in inflammation, blood clotting, and other physiological processes.
Inflammation: Inflammation is a complex biological response of the body's immune system to various stimuli, such as pathogens, damaged cells, or irritants. It is a protective mechanism that helps the body eliminate harmful agents and initiate the healing process.
COX-2: COX-2, or cyclooxygenase-2, is an enzyme that plays a crucial role in the production of prostaglandins, a class of lipid-based signaling molecules involved in various physiological and pathological processes. COX-2 is particularly important in the context of prostaglandins and other eicosanoids, as it is the primary driver of prostaglandin synthesis in response to inflammation and other stimuli.
HPETEs: HPETEs, or hydroperoxyeicosatetraenoic acids, are a class of eicosanoid compounds derived from the oxidation of arachidonic acid. They play a crucial role in the synthesis of various prostaglandins and other eicosanoids, which are important signaling molecules involved in various physiological and pathological processes.
LTB4: LTB4, or leukotriene B4, is a potent inflammatory mediator derived from the metabolism of arachidonic acid through the lipoxygenase pathway. It is a key player in the context of prostaglandins and other eicosanoids, which are important signaling molecules involved in various physiological and pathological processes.
PGE2: PGE2, or prostaglandin E2, is a key eicosanoid that plays a critical role in various physiological and pathological processes within the body. As a member of the prostaglandin family, PGE2 is synthesized from arachidonic acid and acts as a potent signaling molecule, influencing a wide range of bodily functions.
LTA4: LTA4, or Leukotriene A4, is a key intermediate in the biosynthesis of leukotrienes, a class of inflammatory lipid mediators derived from arachidonic acid. It serves as a critical junction point in the eicosanoid pathway, connecting the cyclooxygenase and lipoxygenase branches.
Phospholipase A2: Phospholipase A2 is an enzyme that catalyzes the hydrolysis of the sn-2 ester bond of phospholipids, releasing arachidonic acid and a lysophospholipid. This process is a key step in the production of eicosanoids, such as prostaglandins, leukotrienes, and thromboxanes, which are important signaling molecules involved in inflammation, immune response, and other physiological processes.
LTE4: LTE4, or leukotriene E4, is a potent lipid mediator that belongs to the class of eicosanoids known as leukotrienes. Leukotrienes are inflammatory signaling molecules derived from the metabolism of arachidonic acid, a polyunsaturated fatty acid found in cell membranes.
Biosynthesis: Biosynthesis is the process by which living organisms, such as plants and animals, produce complex chemical compounds from simpler precursor molecules. It is a crucial aspect of biological chemistry that underlies the formation of essential biomolecules, including prostaglandins, terpenoids, and steroids.
Eicosanoids: Eicosanoids are a class of lipid-derived signaling molecules that play crucial roles in various physiological and pathological processes within the body. They are synthesized from arachidonic acid, a 20-carbon polyunsaturated fatty acid, and include prostaglandins, thromboxanes, and leukotrienes.
Cell Signaling: Cell signaling, also known as cell communication, is the process by which cells interact with their environment and coordinate their activities. It is a fundamental aspect of cellular function and is essential for the proper development, growth, and homeostasis of multicellular organisms.
Prostacyclin: Prostacyclin, also known as prostaglandin I2 (PGI2), is a potent vasodilator and inhibitor of platelet aggregation. It is a member of the eicosanoid family of lipid signaling molecules derived from arachidonic acid, and plays a crucial role in regulating cardiovascular function and inflammation.
LXA4: LXA4, or lipoxin A4, is a bioactive lipid mediator that belongs to the class of eicosanoids. It is derived from the omega-6 fatty acid arachidonic acid and plays a crucial role in the resolution of inflammation.
TXA2: TXA2, or thromboxane A2, is a potent vasoconstrictor and platelet-aggregating agent produced by activated platelets. It plays a crucial role in the regulation of blood clotting and vascular homeostasis, and is closely linked to the topics of prostaglandins and other eicosanoids.
LXB4: LXB4, or Lipoxin B4, is a bioactive lipid mediator that belongs to the class of eicosanoids. It is derived from the omega-6 fatty acid arachidonic acid and plays a crucial role in the resolution of inflammation, serving as an anti-inflammatory and pro-resolving signaling molecule within the context of prostaglandins and other eicosanoids.
Celecoxib: Celecoxib is a selective cyclooxygenase-2 (COX-2) inhibitor, a type of nonsteroidal anti-inflammatory drug (NSAID) used to treat pain, inflammation, and other symptoms associated with various conditions, including osteoarthritis, rheumatoid arthritis, and menstrual cramps. It works by selectively inhibiting the COX-2 enzyme, which is responsible for the production of prostaglandins that contribute to inflammation and pain.
COX-1: COX-1, or cyclooxygenase-1, is an enzyme that plays a crucial role in the production of prostaglandins and other eicosanoids, which are important signaling molecules involved in various physiological processes within the body.
Cyclopentane Ring: The cyclopentane ring is a five-membered alicyclic hydrocarbon ring that is an important structural feature in many organic compounds, including prostaglandins and other eicosanoids. Its unique geometry and reactivity make it a crucial component in various biological processes.
Lipoxygenase: Lipoxygenase is an enzyme that catalyzes the dioxygenation of polyunsaturated fatty acids, such as arachidonic acid, to produce a class of lipid mediators called leukotrienes and lipoxins. This enzyme plays a crucial role in the biosynthesis of eicosanoids, which are important signaling molecules involved in various physiological and pathological processes.
Lipoxins: Lipoxins are a class of anti-inflammatory lipid mediators derived from arachidonic acid. They play a crucial role in the resolution of inflammation and the regulation of the immune response within the context of prostaglandins and other eicosanoids.
LTC4: LTC4, or leukotriene C4, is a potent lipid mediator that belongs to the class of eicosanoids known as leukotrienes. Leukotrienes are important signaling molecules involved in various physiological and pathological processes, particularly in the context of inflammation and immune response.
PGI2: PGI2, also known as prostacyclin, is a potent vasodilator and inhibitor of platelet aggregation. It is an eicosanoid, a class of lipid-derived signaling molecules that play crucial roles in various physiological and pathological processes.
NSAIDs: NSAIDs, or non-steroidal anti-inflammatory drugs, are a class of medications that reduce inflammation, pain, and fever by inhibiting the production of prostaglandins, which are key mediators of the inflammatory response. These drugs are widely used to treat a variety of conditions, including arthritis, menstrual cramps, headaches, and other types of pain and inflammation.
Thromboxanes: Thromboxanes are a class of eicosanoid lipid mediators derived from the metabolism of arachidonic acid. They play a crucial role in various physiological and pathological processes, particularly in the regulation of platelet function and vascular homeostasis.
LTD4: LTD4, or Leukotriene D4, is a potent lipid mediator that belongs to the class of eicosanoids known as leukotrienes. Leukotrienes are derived from the metabolism of arachidonic acid and play a crucial role in various physiological and pathological processes, particularly in the context of inflammation and immune responses.