Biochemistry Review: Eicosanoids

[liveonearth]

First, an old post on EFA metabolism is better than this one:
http://liveonearth.livejournal.com/253995.html#cutid1

What are eicosanoids?
biologically active 20c fatty acids

What prostanoids are made from them?
prostaglandins
thromboxanes
leukotrienes

What do these substances do?
act locally as paracrines via g-protein linked cellular receptors
usu cGMP

What are the three series of eicosanoids?
1: linoleic
2: alpha linolenic
3: arachidonic

Which one of the three is conditionally essential?
arachidonic
meat eaters get plenty in diet
can be synthesized from DHGLA in series I if enzyme pathway intact

Each series gives rise to its own set of prostaglandins, leukotrienes and thromboxanes.
Code for those are PG1, LK2, TX3, etc.
Series 2 mostly inflammatory, series 1 & 3 mostly antiinflammatory.

SERIES 1
linoleic acid
omega-6
found in vegetables, seeds, nuts
converted by delta-6 desaturase-->gamma-linolenic (GLA)-->DHGLA-->series 1 cytokines
delta-6 desaturase inhibited by trans fats, stimulated by insulin
GLA found in EPO, borage, black currant???
enzyme for DHGLA-->PG1, TX1 and LK1 is cox or lipox
anti-inflammatory
DHGLA can convert to series 2 which is why arachidonic conditionally essential

SERIES 2
arachidonic acid
sources: animal fats
delta-5 desaturase stim by insulin, blocked by EPA, DHA, glucagon

What is PLA-2?
phospholipase A2
removes lipids from phospholipid bilayer that is the cell membrane
generates arachidonate

What stimulates phospholipase A2?
angiotensin 2, bradykinin, epi, thrombin

What inhibits phospholipase A2?
corticosteroids

What does lipoxygenase make from arachidonate?
leukotrienes

What does cyclo-oxygenase make from arachidonate?
PGs and TXs

What inhibits cyclo-oxygenase?
NSAIDS

SERIES 3
alpha-linolenic acid
omega 3
sources: seed oils: walnuts, flaxseed, perilla, chia, hemp, also green leaves
delta-6 desaturase blocked by stress hormones, age, cancer, stim by B6, Mg, Zn
inhibited by trans fats
alpha linolenic-->EPA-->DHA-->PG, TX, LK 3
EPA in salmon, herring, mackerel