Prostaglandin Biochemistry Quiz Flashcards
PGE3 has a protective effect on vascular epithelia in chronic inflammatory diseases. Eating which of the following would result in the production of PGE3?
A. French fries cooked in corn oil
B. Almonds
C. Cheese
D. Sunflower seeds
E. Swordfish
E. Swordfish
PGE3 is made from ecosapentaenoic acid which is found in fish and algal oils. Seeds, nuts and red meat have very little ecosapentaenoic acid.
A 62-year-old woman with Emphysema is seen by her primary care physician. She is worried that the prolonged use of an inhaled steroid will make her “bulky”. After her physician explains to her that glucocorticoids are not like anabolic steroids and do not cause “bulking up”, they want to explain what the glucocorticoid is doing. Which of the following is an accurate description of the role of the glucocorticoid Cortisol?
A. Cortisol is a natural stimulator of the immune system by inhibiting the synthesis of prostaglandins and leukotrienes that also stimulate the immune system.
B. Cortisol is the natural stimulator of the immune system by stimulating the synthesis of prostaglandins and leukotrienes that usually inhibit the immune system.
C. Cortisol is the natural inhibitor of an overactive immune system by stimulating the synthesis of prostaglandins and leukotrienes that usually inhibit the immune system.
D. Cortisol is the natural inhibitor of an over active immune system by inhibiting the synthesis of prostaglandins and leukotrienes that usually stimulate the immune system.
D. Cortisol is the natural inhibitor of an over active immune system by inhibiting the synthesis of prostaglandins and leukotrienes that usually stimulate the immune system.
Cortisol is a natural regulator of the immune system it inhibits phospholipase A2 thereby inhibiting the production of arachidonic acid. The synthesis of all prostaglandins and leukotrienes requires arachidonic acid as a precursor. Many people hear steroid and think of the androgen that are used by body builders. Glucocorticoids, like cortisol, do not have the same effect as androgens.
A 22-year-old woman presents at 38 weeks gestation with weak uterine contractions. Which of the following could be given to the patient to increase uterine contractions strength?
A. Prostamide F1α
B. Thromboxane A2
C. PGF1α
D. PGE2
E. Leukotriene B4
F. PGI2
D. PGE2
PGE2 is used to soften the cervix which allows for cervical dilation and thereby induces or accelerates labor. It also strengthens contractions.
A 22-year-old woman presents to an ophthalmologist with dry, itchy eyes. The patient has worn contact lenses for myopia for 6 years. Her medical history is otherwise unremarkable. The patient has recently begun using a new type of makeup. Physical examination of her eyes indicates conjunctivitis. Which eicosanoid may be in her new makeup?
A. Prostaglandin G2
B. Prostamide F2α
C. Prostaglandin I2
D. Thromboxane A2
E. Leukotriene D4
B. Prostamide F2α
Bimatoprost is found in some eye lash enhancing makeup and used to lengthen and darken the eyelashes and eye brows. It is the ethanolamine of PGF2, Prostamide F2a. It is also used in the treatment of open angle glaucoma. It alters the fluid maintenance of the eye and can cause red itchy eyes as well as the darkening and lengthening eyelashes and eye brows.
A 36-year old woman comes to the family practice where she has been treated for 8 years for recurring asthma, hypertension and common ailments like influenza. The patient reports that she is worried about her asthma getting worse and she thinks she is developing an allergy to aspirin and Ibuprofen. When she takes 2 aspirin or Ibuprofens for a fever or joint pain after exercise she feels her chest get tight about an hour later. She gets a sinus type headache that begins shortly after her chest tightens. The patient takes 30 mg of lisinopril daily for hypertension, 10 mg of Loratadine for allergies daily and uses a rescue albuterol inhaler as needed for asthma attacks. Physical findings are unremarkable except for nasal polyps, a normal blood pressure and airways are clear. The patient is given an aspirin oral challenge in an outpatient clinic and diagnosed with Aspirin-exacerbated respiratory disease. This disease is caused by aspirin’s effect on prostaglandin synthesis and results in bronchial constriction, headaches, sinus pain and wheezing. What is inhibited by aspirin and why does aspirin cause bronchial constriction?
A. COX1 and COX2 but does not inhibit Lipoxygenase. Lipoxygenase produces leukotrienes which cause smooth muscle constriction.
B. COX2 but not COX1. COX1 leads to the production of PGH2 which a potent vasodilator and bronchodilator.
C. Lipoxygenase which means leukotrienes are not made and cannot relax smooth muscle.
D. Phospholipase A2 which means that PGI2 and PGE2 cannot be made. PGE2 and PGI2 are vasodilators and bronchodilators.
E. COX1 but not COX2. COX2 leads to the production of Thromboxane A2 and PGF2α which are bronchoconstrictors.
A. COX1 and COX2 but does not inhibit Lipoxygenase. Lipoxygenase produces leukotrienes which cause smooth muscle constriction.
Lipoxygenase is unaffected by aspirin whereas both COX1 and COX2 are inhibited. Leukotrienes C, D and E all are implicated in asthma symptoms and cause smooth muscle constriction and thus bronchoconstriction. Phospholipase A2 is not inhibited by aspirin.
Describe the structures of fatty acid precursors of prostaglandins, and their dietary and metabolic sources
Arachidonic acid is the most important substrate because it is more abundant than the others (made via Phospholipase A2 from membrane lipids)
Eicosatrienoic acid: ω-6 oil
Found in nuts, seeds and vegetable oils
Makes PGE1
Arachidonic acid: ω-6 oil
Found in nuts, seeds and vegetable oils
Makes PGE2
Eicosapentaenoic acid: ω-3 oil
Found in fish and algal oils
Makes PGE3
note: the PGE# notates the place of double bonds from starting material
PROSTAGLANDINS OVERVIEW
Not classical hormones, but short-lived paracrine and autocrine messengers made from arachidonic acid
Functions:
- Homeostatic functions specific to different organs
- Mediators of inflammation
Effects are mediated by G-protein coupled receptors
- Platelet aggregation (TXA2)
- Vasodilation (PGE2 , PGI2)
- Uterine contraction (PGE2, PGF2α)
- Reduced gastric acid secretion, enhanced mucus formation (PGE2)
- Inflammation (PGE2, TXA2)
- Fever (PGE2, in preoptic area)
COX 1 vs. COX 2
- COX-2 is induced in response to inflammation, injuries or infections; immune cells
- Makes PGE2 and PGI2
Physiological effects
- increases vasodilation, vascular permeability, cytokine release
- Leukocytemigration
- Pain
COX-2 is induced in response to cytokines; nervous tissue
Physiological effects (PGE2)
- Fever
- Pain
Effects of NSAIDS on COX
Anti-inflammatory steroids (glucocorticoids) inhibit the phospholipase A2 that releases arachidonic acid from membrane lipids. Formation of prostaglandins and leucotrienes is reduced.
Non-steroidal anti-inflammatory drugs (NSAIDs) inhibit cyclooxygenase (either COX-1 or COX-2 or both). They prevent synthesis of prostaglandins but not leucotrienes. They reduce:
- inflammation
- pain
- fever
- platelet aggregation and thrombosis
Pathology: NSAIDs that inhibit COX-1 (aspirin!) can cause gastritis and peptic ulcer, and are contraindicated in asthma.
Aspirin, Ibuprofen, Naproxen, Celebrex, and Arcoxia
Aspirin, Ibuprofen, and Naproxen inhibit both COX-1 and COX-2
- Reduce inflammation by inhibiting the thromboxane and prostaglandin synthesis
- Decreases clotting (“thin the blood”) ➡ Thromboxane A2 (TXA2) promotes platelet aggregation via upregulating the expression of glycoprotein IIa/IIb
- Sensitivity occurs in aspirin-exacerbated respiratory disease, AERD
➡Symptoms of Asthma or seasonal allergies
➡COXs inhibited but not LOX
➡Leukotrienes, LTC4, LTD4 and LTE4, implicated in the pathophysiology of asthma and seasonal allergies.
• Celebrex and Arcoxia are specific for the inhibition of COX-2 therefore they do not have
Important product of COX pathway and general structural feature
PGH2 is the first stable product in prostaglandin synthesis. It is converted to other prostaglandins by tissue-specific enzymes
Important product of LOX pathway and general structural feature
Leukotrienes: important mediators of leukocyte accumulation during acute inflammation; contract bronchial SM and contribute to asthma
