Ecosanoids: Nishimoto Flashcards

1
Q

Name the 3 Eicosanoid derivatives.

A

Prostaglandins
Leukotrienes
Thromboxanes

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2
Q

Type of eicosanoid secreted by a cell depends on the cell type and its enzymes. With that in mind, what eicosanoid derivatives do endothelial cells secrete?

A

Prostaglandins- inhibit coagulation

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3
Q

WHat type of eicosanoid to platelets make/secrete?

A

Thromboxanes - stimulate aggregation and clotting

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4
Q

What fatty acid is the precursor to eicosanoids?

A

Arachidonic Acid

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5
Q

Can arachidonic acid be synthesized in the body? If so, how?

A

Yes, from 18-C FA’s like Oleic acid and alpha-linoleic acid. Add 2 C with ELONGASE enzyme and BOOM! Arachidonic Acid.

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6
Q

Arachadonic acid is polyunsaturated. How many double bonds does it have?

A

4

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7
Q

Before incorporating itself into membrane phospholipids, what happens to Arachidonic acid?

A

It is activated by AcetylCoA

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8
Q

What is the major regulatory step of Eicosanoid synthesis?

A

The release of Arachidonic acid from the membrane by PHOSPHOLIPASE A2.

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9
Q

What inhibits Phospholipase A2?

A

Glucocorticoids - specifically Lipocortin. Glucocorticoids bind receptor and cause transcription of Lipocortin.

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10
Q

If Arachidonic Acid is acted on by lipoxygenase, what is the product? (general)

A

Leukotrienes
HETE
Lipoxins

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11
Q

If Arachidonic Acid is acted on by Cyclooxygenase and Peroxidase, what is the intermediate formed?

A

Prostaglandin H2 (PGH2)

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12
Q

PGH2 is a common precursor of what products?

A

Prostacyclin and other prostaglandins, and Thromboxanes.

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13
Q

Release of ArA from membranes is triggered by….

A

Hormonal stimuli: Epinephrine, Thrombin, Antigotensin II

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14
Q

What are the essential fatty acids we must ingest for the synthesis of eicosanoids?

A

Omega 3 and 6

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15
Q

If Arachidonic acid is acted on by CYP450 what is the product?

A

Epoxides

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16
Q

By what mechanism do PGD, PGI,and PGE work?

A

The Adenylyl Cyclase pathway. cAMP and PKA.

17
Q

What eicosanoid derivatives work by increasing cytosolic calcium?

A

PGF2, TXA2, and Leukotrienes

18
Q

How long is the lifespan of an eicosanoid?

A

Seconds to minutes. SHORT.

19
Q

Which Prostaglandin is more reduced? PGA or PGF?

A

PGF is most reduced. PGA is most oxidized.

20
Q

What does the number at the end of a prostaglandin abbreviation indicate?

A

The number of double bonds contained within that prostaglandin and its precursor.

21
Q

PGI PGE and PGD cause what to happen?

A

Vasodilation and adenylyl cyclase pathway

Inhibit: Platelet aggregation, leukocyte agregation, and lymphocyte migration.

22
Q

What eicosanoid is secreted by platelets? What does it do?

A

Thromboxane A2. (TXA2) - stimulates aggregation, causes vasoconstriction.

23
Q

What does PGF2-alpha do?

A

VasoCONSTRICTION, bronchoCONSTRICTION, and smooth muscle contraction

24
Q

What prostaglandins do vascular endothelial cells secret?

A

PGI
PGE
PGD

25
Q

NSAIDS inhibit what, in the synthesis of PGH2?

A

Cyclooxygenase

26
Q

What cells synthesize leukotrienes?

A

Leukocytes

27
Q

What enzyme catalyzes the reaction of arachidonic acid into leukotrienes?

A

Lipoxygenase

28
Q

What is a common intermediate of both HETEs and Leukotrienes?

A

HPETE

29
Q

What is a lipoxin?

A

A derivative of Arachidonic acid with 3 -OH groups

30
Q

How do lipoxygenases work on ArA?

A

They introduce an unstable proxy oxygen into the structure to make HPETE, which quickly rearranges into either Leukotrienes or HETEs.

31
Q

What is the role of Leukotrienes in the inflammatory response?

A

increase vascular permeability, recruits WBCs to the area, IL-1, IL-2.