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FOS 2 > Lipid Signaling > Flashcards

Lipid Signaling Flashcards

1
Q

Most histamine is generated in granules in ___ or ____

A

Mast cells

Basophils

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2
Q

What triggers degranulation?

A

Allergic reactions

Anaphylaxis

Celllar destruction

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3
Q

Signaling molecules that are stored (ex: histamine) are _____.

A) Hydrophobic

B) Hydrophilic

C) Liphophilic

D) Lipophobic

A

D

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4
Q

Are lipid signaling molecules stored in the body?

A

No - most are generated on - demand from phospholipid precursors

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5
Q
A
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6
Q

Describe how arachidonic acid is liberated from the cell membrane.

A

Trauma –> release of histamine –> histamine binds to H1 receptor (Gaq receptor) –> aq subunit stimulates PLC –> PLC cleaves PIP2 into DAG and IP3 –> IP3 stimulates Ca2+ release which stimulates PLA2 which increases arachidonic acid production –> DAG is acted upon by DAG lipase which produces AA and mAA

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7
Q

What is a eicosanoid?

A

Signaling molecule made of 20 carbon fatty acids

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8
Q

How does arachidonic acid relate to eicosanoids?

A

AA is the main precursor for eicosanoids

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9
Q

How is PLA2 stimulated?

A

Phosphorylation and Ca2+ release

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10
Q

What is a leukotriene?

A

Structure with conjucated triene system of double bonds produced by white blood cells

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11
Q

How do leukotrienes relate to Arachidonic acid?

A

Leukotrienes synthesized from AA by lipoxygenease pathways.

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12
Q

Lipoxygenases synthesize leukotrienes from arachidonic acid. Where are these enzymes primarily located?

A

Platelets, lungs, mast cells, WBC

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13
Q
  1. 5-lipoxygenase is the main enzyme that produces leukotrienes. What is its substrate and what is the product?
  2. What is the product converted to?
A
  1. Substrate: 5-HpETE Product: LTA4
  2. LTA4 –> LTB4 or cysteinyl-leukotrienes
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14
Q

Where is LTB4 metabolized?

A

By membrane bound cytochrome P450 in neutrophils

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15
Q

Leukotriene receptors are termed ___ if their ligand is LTB4 and _____ if their ligand is cysteinyl-leukotrienes.

A

BLT

CysLT

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16
Q

Stimulation of BLT receptors results in what in terms of an immune response? (4)

A

Adherence

Chemotaxis

Activation of neutrophils + monocytes

Stimulates proliferation and cytokine production

17
Q
  • Stimulated of CysLT receptors causes what in terms of a physiologic response? (2)
A
  • Bronchoconstriction
  • Vasodilation everywhere except the heart and lungs, in which it causes vasoconstriction
18
Q

Stimulation of BLT receptors is an important mediator of ______.

Stimulation of CysLT receptors is an important mediator of _____.

A

Inflammation

Asthma

19
Q

LTB4 is a potent ______ agent for neutrophils and macrophages.

A

Chemotactic

20
Q

Arachidonic acid can be acted upon by cyclooxygenases as well as lipoxygenases.

  • COX 1 is present in ___ cells and is ____ expressed and produces ____
  • COX 2 is _____ normally present, but is ____ by inflammatory stimuli
A
  • most, constitutively, prostanoids
  • not, strongly induced
21
Q

Position 523 in the COX 1 and COX 2 primary amino acid sequence is important for its catalytic function.

  • What AA is present in COX 1 vs. COX 2 at this position?
  • What effect does this single AA change have on the COX 1 vs. COX 2 function?
A
  • COX 1 = Ile COX 2 = Val
  • Val is smaller than Ile and allows COX 2 to access hydrophobic side pocket in enzyme which is sterically hindered in COX 1
22
Q

What are the 5 bioreactive end products of COX 1 and COX 2 acting on arachidonic acid?

A

PGE2

PGI2

PGD2

PGF2alpha

TXA2

23
Q

Before arachidonic acid is converted to bioreactive prostaglandins, it is converted to 2 unstable and highly reactive prostaglandins ____ and ____.

A

PGG2 and PGH2 (ultimately what can become bioreactive prostaglandins)

24
Q

TXA2 has what effect on the vascular system and respiratory system?

A
  • Vasoconstriction and prothrombotic agents
  • Bronchoconstriction
25
Q

PGF2 has what effect on the uterus?

A

Constricts myometrial smooth muscle to help shed endometrial lining

26
Q

What effect does PGE2 have on the GI system and the hypothalamus?

A
  • Increased gastric acid secretion, mucus secretion, and bicarbonate secretion –> protects stomach
  • Increased thermoregulatory setpoint
27
Q

What effect does PGD2 have on the uterus?

A

Relaxes the smooth muscle of the uterus

28
Q

What effect does PGI2 have on the cardiovascular system?

What is a synonym for this prostaglandin?

A

Vasodilation and antithrombosis

Prostacyclin

29
Q

Increased PGI2 results in increased ___.

A

Bradykinin –> vasodilation, increased pain sensitization

30
Q

Describe the half life of prostaglandins.

A

They are synthesized from prostanoic acid and rapidly taken up and inactivated.

31
Q

THC is a lipophilic endocannabinoid. It binds to 2 receptors, CB1 and CB2. CB1 is found in the ____ and CB2 is found in the ____.

A

CNS

Peripheral tissues

32
Q

How do endocannabinoids relate to arachidonic acid?

A

Endocannabinoids –> metabolized to anandamide –> metabolized to arachidonic acid–> acted upon by COX and LOX

33
Q

What effect do endocannabinoids have on leukocytes and inflammation?

A

They act on leukocytes to oppose the action of proinflammatory and chemotactic stimuli (oppose LTB4 action) supplying stop signals to dampen immune response

34
Q

On the surface, it seems contradictory that endocannabinoids are metabolized to arachidonic acid, which is further metabolized to prostaglandins and leukotrienes that mediate inflammation and pain sensitization, yet the physiological response to endocannabinoids is pain relief. Explain how this is possible.

A

The binding of endocannabinoids to CB1 and CB2 receptors in CNS and PNS results in anti-inflammation and chemotactic stimuli which far outweighs the proinflammatory and pain sensitization caused by prostaglandins and leukotrienes.

35
Q

Describe how acetaminophen exerts analgesic effects.

A

It inhibits the reuptake of endogenous canabinoids by neurons thus increasing endocannabinoid signaling effects. Because endogenous cannabinoids last longer in the neurons, the CB1 receptors are able to exert greater effects. Endocanabinoid binding to CB1 causes hyperpolarization of pain sensing neurons resulting in analgesia.

36
Q

What are the 3 eicosanoids that were discussed in this block?

A

Leukotrienes

Prostaglandins

Thromboxanes

FOS 2 (44 decks)

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