Eicosanoids Flashcards
Arachidonic acid
20:4w6—20 carbons long 4 double bonds with the first being 6 carbons from omega
Stored in membrane phospholipids and is the precursor for eicosanoids, potent local hormones
w3 analogs produce related compounds—EPA and DHA.
Can be made from linoleic acid 18:2w6, so technically not essential but only if you eat enough of it to spare
Eicosanoids
Potent lipid local hormones made from fatty acid
Arachidonic acid metabolites
w3 vs w6 fatty acids
All w3 And w6 fatty acids are essential fatty acids, EFA
We cannot make them and we must eat the
They compete for enzymes that make eicosanoids, some metabolites have different effects
Saturated fatty acids
Single bonds
Bad fats, solid at room temperature
High saturated fat: animal fat
Unsaturated fatty acids
Good fats
Double bonds
Vegetable oils, plant oils
Exception: tropical oils are healthy but almost completely saturated such as coconut oil and palm oil
Prostaglandins and related eicosanoids
Extremely potent arachidonate metabolites
Short lived and in small amounts, difficult to study
Act locally where made, not transported in blood and act immediately then destroyed
Side range of physiological responds
Involved in inflammation, fever, pain, blood clotting, immune responses to cancer and asthma
Eicosanoid biosynthesis
Via phospholipids A2, PLA2
Converts a phospholipid into arachidonicmacid
Common precursors to the cyclooxygenase and lipoxygenase enzymes
These specific species produced depends on cell specific repertoire of synthetic enzymes
Most control at PLA2, amount of eicosanoid produced depends on amount of AA released
Eicosanoid signaling pathway
Signal activates PLA2 which releases AA from the membrane phospholipids
COX enzyme starts the synthesis of some eicosanoid
Product is transported out of the cell and binds some receptor on the same cell or another close by
G protein signaling mechanism activates the second messenger which activates a psychological effect
Sites for PLA2
Outer nuclear membrane
ER
Plasma membrane
Multiple pathways: cyclooxygenase or lipoxygenase
Eicosanoid biosynthesis and drugs
Esterified arachidonic acid is converted to arachidonic acid by PLA2
This then either goes to lipoxygenase or cyclooxygenase which leads to a whole host of eicosanoid
Steroidal anti-inflammatory drugs inhibit PLA2
Non-steroidal anti-inflammatory drugs block COX and the synthesis of prostaglandins and thromboxanes
Anti-asthmatics block lipoxygenases
PG/TX asthmatics agonist/antagonists too
Aspirin
Rheumatism: muscle and joint aches and pains since ancient times
Ue of willow and or myrtle leaves and bark to treat this
Hippocrates and Galen have recipes involving willow bark
Hoffman acetylates salicylic acid and invents aspirin
A great anti-inflammatory agent
Cyclooxygenase isozymes COX-1 and COX-2
Tissue specific COX localization, tissue specific synthetases—-> tissue specific eicosanoids
COX1: most cells, protects stomach lining
COX2: inducible in macrophages, inflammatory response
Aspirin inhibits both, great anti-inflammatory agent but sometimes produces ulcers
There are selective COX2 inhibitors which are great anti-inflammatory agents and do not give ulcers, no COX1 inhibitors
BUT
COX1: platelets, produce TXA2, positive platelet aggregation
COX2: vascular endothelial cells, produce PGI2, negative platelet aggregation
