PS, PI, and PG pt 2 Flashcards
what are ehter linked lipids
Ether-linked lipids are primarily a
specialized group of PL that account for
~20% of all of the classes of PL in vivo
ether linked lipids structure
The ether-linked lipids have an ether bond
in the sn-1 position that can also be
accompanied without (termed plasmanyl)
or with (termed plasmalogen) a 1′ cis
double bond
– An ether with a 1′ cis double bond is better
known as a vinyl ether
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absence of ether linked lipids
To an individual cell, the absence of ether-
linked lipids is not lethal
* However, the absence of ether-linked
lipids is detrimental to tissues
disruptions of ether linked lipids in mice
Disruption of their synthesis in mice leads to
impaired neurological and eye development
disruption of ether linked lipids in humans
In humans, extremely rare genetic defects in
ether-linked lipid synthesis leads to impaired
brain development, rhizomelia (truncated limb
bones), and infantile death
where are ether linked lipids found
Ether-linked lipids exist in many tissues and in the plasma via lipoproteins
* Of interest:
– Tissues typically have ethanolamine plasmalogens, but the heart has a disproportionately higher amount of choline plasmalogens vs. ethanolamine plasmalogens
– 10% of PL on lipoproteins are ethanolamine based… 1/2 of
this is ethanolamine plasmalogen via ONLY the liver (a tissue with one of the lowest levels of plasmalogens)
what does the synth of ether linked lipids require
The synthesis of ether-linked lipids
requires fatty alcohols
– Fatty alcohols are also precursors for the
formation of most waxes
what are the two types of acyl CoA reductases that exist
– Acyl-CoA reductase 1
– Acyl-CoA reductase 2
what does acyl coa reductase 1 do
Acyl-CoA reductase 1 primarily reduces
C16 and C 18 unsaturated fatty acids
what does acyl coa reducatase 2 do
Acyl-CoA reductase 2 reduces all
saturated fatty acids
what does CDP-ethanolamine: 1alkyl-2-acyl-sn-glycerol ethanolaminephoshpotransferase do
attaches ethanoamine to phosphate
what does CDP- choline:1-alkyl-sn-glycerol cholinephosphotransferase do
attatches choline to phosphate
what is plasmanyl do
plasmanylethanolamine
wat is plasmalogen
ethanolamine plasmalogen
what is PAF- and what is it produced by
platelet activating factor
PAF is a plasmanylcholine produced by
endothelial cells and various white blood
cells (basophils, neutrophils, monocytes,
macrophages, mast cells)
what does PAF do
PAF triggers extremely potent pathological
responses associated with asthma,
hypertension, inflammation, allergic
responses, and anaphalaxis with as little
as 100 pM in the bloodstream
how is PAF synthesized
remodelling route
de novo route
remodelling route of PAF synth
Remodeling route: activated by inflammatory
events & primary route for pathogenesis
* The fatty acid in the sn-2 position of
plasmanylcholine is rapidly replaced with acetate
de novo route of PAF synth
De novo route: maintains minimal
concentrations to regulate normal cellular
functions
* Synthesized over several steps starting with a
lyso-plasmanyl acid
PAF and bronchoconstriction
increase
PAF and pulmonary resistance
increase
PAF and lung compliance
decrease
PAF and pulmonary edema
increase
PAF and hypertension
increase
PAF and heart rate
increase
PAF and hypersensitivity
increase
PAF and intracellular [Ca++]
increase
PAF and superoxide synth
increase
PAF and eicosanoid synth from arachidonate
increase
PAF and phosphoinositude utilization
increase
PAF and pro-inflammatory cytokine synth
increase
PAF and anti inflammatory cytokine synth
decrease
what are the functions of plasmalogens
Not really clear, but current studies
suggest:
– Plasmalogens are typically enriched with
PUFAs, thus they are believed to act as a
supply of essential fatty acids during dietary
fatty acid deficiency
– It is also believed that the vinyl ether bond
acts as an antioxidant to scavenge damaging
reactive oxygen species