Ans
:- PAF content of human sperm has a positive correlation with fertilizing
potential and pregnancy outcome. Produced by variety of cell types. Several studies
suggest that PAF appears to mediate sperm motility by inducing the formation of
inositol triphosphate and diacylglycerol and by increasing intracellular
calcium. PAF content of human sperm has a positive correlation with fertilizing
potential and pregnancy outcome. Platelet-activating factor, also known as PAF, PAF-acether or AGEPC (acetyl-glyceryl-ether-phosphorylcholine), is a
potent phospholipid activator
and mediator of many leukocyte functions, platelet aggregation and
degranulation, inflammation,
and anaphylaxis. It is also involved in changes to
vascular permeability, the oxidative burst, chemotaxis of leukocytes, as well
as augmentation of arachidonic acid metabolism
in phagocytes.. Cllinical
High
PAF levels are associated with a variety of medical conditions. Some of these
conditions include:
•Allergic
reactions
•Stroke
•Sepsis
•Myocardial infarction
•Colitis, inflammation of the large intestine
•Multiple sclerosis
•Stroke
•Sepsis
•Myocardial infarction
•Colitis, inflammation of the large intestine
•Multiple sclerosis
While
the effects that PAF has on inflammatory response and cardiovascular conditions
are well understood, PAF is still a hot subject for discussion. Over the past
15 years, papers written on PAF have almost doubled from approximately 7,500 in
1997 to 13,000 in 2012.[citation
needed] Research into PAF is ongoing.
Anti-PAF
drugs
Anti-PAF
drugs are currently being used in cardiac rehabilitation trials. Anti-PAF drugs
are used to block angiotensin II type 1 receptors to lower in the risk of
atrial fibrillation in individuals with paroxysmal fibrillation. It is also
used to lessen the effects of allergies.
PAF
is produced by a variety of cells, but especially those involved in host
defense, such as platelets, endothelial cells, neutrophils, monocytes, and macrophages. PAF is continuously produced by
these cells but in low quantities and production is controlled by the activity
of PAF acetylhydrolases. It is produced in larger quantities by inflammatory
cells in response to specific stimuli.[1] AF is produced by stimulated
basophils, monocytes, polymorphonuclear neutrophils, platelets, and endothelial
cells primarily through lipid remodeling. A variety of stimuli can initiate the
synthesis of PAF. These stimuli could be macrophages going through phagocytosis
or endothelium cells uptake of thrombin.
There are two different pathways in which PAF can be
synthesized: de novo pathway and remodeling. The remodeling
pathway is activated by inflammatory agents and it is thought to be the primary
source of PAF under pathological conditions. The de novo pathway
is used to maintain PAF levels during normal cellular function.
The most common pathway taken to produce PAF is remodeling. The
precursor to the remodeling pathway is a phospholipid, which is typically
phosphatidylcholine (PC). The fatty acid is removed from the sn-2 position of
the three-carbon backbone of the phospholipid by phospholipase A2 (PLA2) to produce
the intermediate lyso-PC (LPC). An acetyl group is then added by LPC
acetyltransferase (LPCAT) to produce PAF.
Using the de novo pathway, PAF is produced
from 1-O-alkyl-2-acetyl-sn-glycerol (AAG).
Fatty acids are joined on the sn-1 position with 1-O-hexadecyl being the best
for PAF activity. Phosphocholine is
then added to the sn-3 site on AAG creating PAF.
The concentration of PAF is controlled by the synthesis of the
compound and by the actions of PAF acetylhydrolases (PAF-AH). PAF-AH are a
family of enzymes that have the ability to catabolize and degrade PAF and turn
it into an inactive compound. The enzymes within this family are lipoprotein-associated
phospholipase A2, cytoplasmic platelet-activating factor acetylhydrolase 2,
and platelet-activating factor acetylhydrolase 1b.
Cations are one form of regulation in the production of PAF.
Calcium plays a large role in the inhibition of enzymes that produce PAF in
the denovo pathway of PAF biosynthesis.
The regulation of PAF is still not completely understood.
Enzymes that are associated with the production of PAF are controlled by
metal ions, thiol compounds, fatty acids, pH,
compartmentalization, and phosphorylation and dephosphorylation. These controls
on these PAF producing enzymes are believed to work in conjunction to control it,
but the overall pathway and reasoning is not well understood.
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