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BC3004: Cell Signalling > Eicosanoids > Flashcards

Eicosanoids Flashcards

1
Q

What are the FOUR subfamilies of Eicosanoids?

A
  1. Prostaglandins
  2. Prostacyclin
  3. Thromboxanes
  4. Leukotrienes
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2
Q

What is the structure of Eicosanoids?

A

20-carbon fatty acid derivative

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3
Q

What are Eicosanoids synthesised from?

A
  • Polyunsaturated fatty acids
  • Particularly Arachidonic Acid
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4
Q

What is the structure of Arachidonic Acid?

A

20 C:4 unsaturated bond structure

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5
Q

Are Eicosanoids soluble in water?

A

No.
Poorly soluble in water

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6
Q

What are the functions of Eicosanoids?

A

Act as autocrine or paracrine local mediators

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7
Q

Where do Eicosanoids bind to receptors?

A

Cell surface

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8
Q

What receptors do Eicosanoids bind and how does signalling occur?

A

7-TM receptors and signalling occurs via heterotrimeric G-proteins (GCPRs)

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9
Q

What biological functions are Eicosanoids involved in?

A
  • Inflammation
  • Pain sensation
  • Platelet aggregation
  • Asthma
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10
Q

Are Eicosanoids stored or produced on demand?

A

Produced on demand

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11
Q

When are Eicosanoids synthesised?

A

When a cell is activated by mechanical trauma, growth factors, cytokines, or other stimuli

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12
Q

How is the rate of release of Eicosanoids determined?

A

Mainly by rate of synthesis, which is dependent on availability of precursor (arachidonic acid)

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13
Q

What type of fatty acid is Arachidonic Acid?

A
  • Essential fatty acid
  • Cannot be synthesised from scratch
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14
Q

Where is Arachidonic Acid normally present?

A

In cells that are esterified at the 2-position in phospholipids

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15
Q

How is Arachidonic Acid released from phospholipids?

A

By the action of phospholipase A2 (PLA2) enzymes

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16
Q

What is the mechanism of action in the production of Eicosanoids from Arachidonic Acid?

A
  1. Arachidonic Acid released at ER and nuclear membranes by PLA2 and presented to prostaglandin H synthase (PGHS / COX)
  2. PGHS / COX converts arachidonic acid to prostaglandin H2 (PGH2)
  3. Enzymatically catalysed reduction or isomerisation of PGH2 generates eicosanoids
17
Q

How is PLA2 regulated?

A

Phosphorylation and an influx of Ca2+ which triggers PLA2 activation and translocation to the nuclear membrane

18
Q

Which amino acid does phosphorylation of PLA2 occur on?

A

Serine-505

19
Q

What causes the phosphorylation of PLA2?

A

Result of ligand binding to receptors such as the interferon receptors, mGLUR1, etc

20
Q

What inhibits PLA2 and reduces inflammation?

A

Glucocorticoids stimulate the release of lipoprotein

21
Q

How is Arachidonic Acid generated?

A
  • By the action of Phospholipase C (PLC) on phospholipids to form DAG
  • Cleaved by DAG lipase to form Arachidonic Acid and monoacylglycerol
22
Q

What are the TWO isoforms of Prostaglandin H synthase?

A
  1. COX-1
  2. COX-2
23
Q

What is the function of COX-1?

A

Responsible for basal prostaglandin synthesis

24
Q

What is the function of COX-2?

A

Important for induced prostaglandin synthesis (inflammatory response)

25
Q

What major group of anti-inflammatory drugs target Eicosanoid biosynthesis?

A

Non-Steroidal Anti-Inflammatory Drugs (NSAIDs)

26
Q

What do NSAIDs target in Eiscosanoid biosynthesis?

A

COX-1 and COX-2

26
Q

Which isoform of Prostaglandin H synthase is the target preference for NSAIDs in Eicosanoid biosynthesis?

A

COX-2

27
Q

Which classical NSAIDs inhibit COX-1 and COX-2?

A

Aspirin and Ibuprofen

28
Q

What causes the anti-coagulant properties of Aspirin?

A

Inhibits the formation of Thromboxane A2
* released by platelets and causes aggregation

29
Q

TRUE OR FALSE:
Eicosanoids often act in agonist pairs

A

False.
Act in ANTAGONIST pairs

30
Q

How are Leukotrienes synthesised?

A

By Lipo-Oxygenases

31
Q

How are Leukotrienes modified?

A

Conjugation to more polar molecules such as Glutathione (Leukotriene C4) or Cysteinylglycine (Leukotriene D4)

32
Q

How do Leukotrienes affect airway smooth muscle?

A

Cause contraction
(LTD4)

33
Q

What are TWO examples of lipophilic hormones that bind cell surface receptors?

A
  1. Platelet Activating Factor (PAF)
  2. Lysophosphatidic Acid (LPA)
34
Q

What effect does Lysophosphatidic Acid (LPA) have on target cells?

A
  • Stimulation of growth
  • Cell division
  • Transformation
  • Alteration of cell morphology

BC3004: Cell Signalling (18 decks)

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