Everything about Platelet-activating Factor totally explained
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Platelet-activating factor, also known as a
PAF,
PAF-acether or
AGEPC (acetyl-glyceryl-ether-phosphorylcholine) is a potent
phospholipid activator and mediator of many leukocyte functions, including
platelet aggregation,
inflammation, and
anaphylaxis.
It is produced in response to specific stimuli by a variety of cell types, including
neutrophils,
basophils,
platelets, and
endothelial cells.
Chemistry
Several molecular species of platelet-activating factor have been identified which vary in the length of the O-alkyl
side chain.
- Its alkyl group is connected by an ether linkage at the C1 carbon to a sixteen carbon chain.
- The acyl group at the C2 carbon is an acetate unit (as opposed to a fatty acid) whose short length increases the solubility of PAF, allowing it to function as a soluble signal messenger.
- The C3 has a phosphocholine head group, just like standard phosphatidylcholine.
Function
It is an important mediator of
bronchoconstriction.
It causes platelets to aggregate and blood vessels to dilate. At a concentration of 10^-12 M, PAF causes life threatening inflammation of the airways to induce
asthma like symptoms.
Toxins such as fragments of destroyed bacteria induce the synthesis of PAF, which causes a drop in
blood pressure and reduced volume of blood pumped by the heart, which leads to
shock and maybe death.
History
It was discovered by French immunologist
Jacques Benveniste in the early 1970s. Its structure was elucidated by Constantinos A. Demopoulos in 1979.
Biosynthesis and degradation
PAF is biosynthesized from
lysophosphatidylcholine (LPC) and
acetyl CoA by the enzyme
LPC acetyltransferase (LPCAT).
It is degraded (thereby terminating its capacity to act as a signaling molecule) by a group of enzymes called
PAF acetylhydrolases (PAFAHs) which are related to
phospholipase A2.
Antagonists
SM-12502 is a PAF antagonist, which is metabolized in the liver by the enzyme CYP2A6. Further Information
Get more info on 'Platelet-activating Factor'.
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