Eicosanoids, Omega 3 Derivatives, and Membrane Lipids

What are eicosanoids? 

Paracrine hormones

When are eicosanoids released?

In aresponse to stimulus (injury, clotting factors, endocrine hormones

Where are responses elicited for eicosanoids

Paracrine (nearby) cells

How many carbons in Eicosanoids?

20

What are eicosanoids derived from?

arachidonic acid

Where is arachidonic acid sourced from? 

Diet or synthesized by elongation and desaturation of linoleate

What does eicosanoids regulate?

Inflammation, blood clotting, and smooth muscle contraction

What releases and incorporates arachidonic acid?

Phospholipase A2

Where on glycerophospholipids are arachidonic acids incorporated?

C2

What inhibits some isoforms of phospholipase A2? 

Anti-inflammatories steriods (corticosteriods)

What else can stimulate Arachidonic acid?

Sequential activities of phospholipase C and diacyglycerol lipase

What are the pathways for arachidonic acid

Lipoxygenase, cytochrome P450, and cycloxygenase

What ddoes the cycloxygenase pathway produce?

PGH2, prostaglandins, and thromboxanes

What does the lipoxygenase pathway produce? 

HPETE, HETE, Lipoxins, and Leukotrienes 

What does the cytochrome P450 pathway produce?

Epoxides, diHETE, and HETE

What catalyzes prostaglandins and thromboane synthesis?

PGH synthase

How many catalytic sides does PGH have?

two

What does PGH synthase produce? 

PGH2

What does the COX catalyze?

Formation of a peroxide and a cyclic peroxide

At what carbon does COX produce a peroxide?

C15

What does the peroxidase active site do? 

Reduces peroxide 

At what carbon does the peroxidase active site reduce peroxide?

C15

What does the peroxidase active site use to reduce peroxide?

GSH

When is thromboxane produced?

Time of endothelial injury

When is prostacyclin produced?

As clot formation ends

What do NSAIDS do? 

Inhibit PGH synthase

What are the two main isozymes of COX active site?

COX-1 anf COX-2

when is COX-1 expressed?

Constitutively

What is COX-1 important for?

General cell function

When is COX-2 repressed 

Induced in limited number of tissues

What does COX-2 cause?

Increased prostaglandin synthesis

What does increased prostaglandin synthesis result in?

Pain, heat, redness, and swelling

What can long term use of NSAIDS result in?

Gastric bleeding and impaired blood clotting

What is PGH2 the precursor for 

All series-2 prostaglandins

What do all prostaglandins contain?

Cyclopentane ring

What does the letter following PG mean

modifications to the ring

What does the subscript on the PG indicate

number of double bonds in the non-ring portion of the structure

What are derivatives of arachidonic acid members of? 

series 2-prostaglandins

Whaat does PGI2, PGE2, and PGD2 do?

Increase vasodialation, cAMP and decrease platlet aggregation, leukocyte aggregation, IL1 and IL2, T-cell creation, lymphcyte migtation

What does PGF2 do?

Increase vasoconstriction, bronco-constriction, and smooth muscle contration

What is PGH2 a precursor for, aside from prostaglandins

Series-2 thromboxanes.

Whay do alal thromboxanes contain? 

6-membered cyclic ether

What does the last letter in the name of a thromboxane indicate?

Modifications to the cyclic portion of the structure

What does the subscript on a thromboane indicate?

Number of double bonds

What does TXA2 strimulate?

Platelet aggregation and formation of thrombus

How does low-dose asprin therept for the prevention of MI work? 

inhbits TXA3, and preventing thrombus formation at ruptered artherosclerotic plaques 

What are peroxides reduced to?

alcohol and other modefictions

What is HPETE

Hydroperoxyeicosatetraenoic acid

What is HETE

Hydroxyeicosatetraenoic acid

What is 5-HPETE and 5-HETE

Leukotrienes 

How many double bonds will leukotrienes have at least

3

Where are leukotriene double bonds not close to

methyl end

What functional groups should leukotrienes have

hydroxyl or epoxide functional groups

What can be attached leukotrienes

glutathione or cysteine 

What are leukotrienes mediators of

Allergic response and inflammatikon

Activation of what stimulates production of leukotrienes in leukocytes?

5-lipoxygenase

What does leukotriene production in leukocytes cause?

Bronchoconstriction and inflammation in asthma

What do drugs treating asthma inhibit?

Leukotriene synthesis or leukotriene receptors