PS, PI, and PG synth and fn Flashcards
What does PS mean
phosphatidylserine
PS accounts for _ of the total PS in mamalina cells
PS accounts for 3-10% of the total PL in
mammalian cells
– PC (60-85%); PE (10-30%)
what are the precursors for PS synth
In mammals, PC & PE are the precursors
for PS synthesis
PS synthesis from PC & PE requires
PS synthesis from PC & PE requires Ca ++
and phosphatidylserine synthase (PSS)
PSS- phosphatidylserine synthases
how many exist in mammals
Two PSS exist in mammals: PSS1 and
PSS2
PSS1 and PSS2 uses
PSS1
uses only PC for PS synthesis, and that
PSS2 uses only PE for PS synthesis
AA sequences bw PSS1 and PSS2
The amino acid sequences between PSS1
and PSS2 are 30% identical, but little is
known about their protein structures and
how they function
where is PSS1 expressed
PSS1 is ubiquitously expressed in vivo
where is PSS2 found
PSS2 is in most PSS1 tissues but highly
expressed in Sertoli cells within testes
PSS1 knockout mice are
PSS1 knockout mice are viable and they
appear phenotypically norma
male PSS2 mice
Male PSS2 knockout mice have smaller
testes and up to half are infertile
However, tissue levels of PC, PS, and PE in the PSS2 knockout tissues
However, tissue levels of PC, PS, and PE
in the PSS2 knockout tissues are normal
The mechanisms that regulate PS synthesis
The mechanisms that regulate PS
synthesis are unknown:
DHA and PS
DHA (22:6n-3) is highly incorporated into PS
within the brain… DHA deficiency reduces
neuronal PS levels
how does PS relate to PSS1 and PSS2 activities
PS appears to directly regulate the enzyme
activities of PSS1 and PSS2:
* high levels of PS reduce the rate of PS synthesis
what does PS activate
PS is required to activate several intracellular molecules
– ie. protein kinase C, sphingomyelinase, and
Na+ /K+ ATPase
where is PS found
PS is typically found intracellularly and on
the inner leaflet of cell membranes
what is the purpose of PS being on theouter cell membrane leaflet
Exposure of PS on the outer cell membrane
leaflet is a marker of cell apoptosis that is
recognized by macrophages (that engulf the
cell)
PI accounts for _ of the total PL in
mammalian cells
up to 10%
how essential is PI
PI is essential for all species
– ie. Deletion of PI synthase in yeast is lethal
What is PI
phosphatidylinositol
where does inositol come from
Inositol comes from either diet or de novo synthesis
– Inositol is synthesized from glucose-6- phosphate
what are the functions of PI
- PI is a precursor to several fast-acting
intracellular signaling molecules,
collectively called phosphatidylinositides - Phosphatidylinositides are derived via the
phosphorylation of the –OH groups on the
inositol head group
PG and its derivatives account for _ of
the total PL in most mammalian cells
<1%
– Exceptions: PG and its derivatives account for
2-18% of total PL in various cell types within the lung – it is a component of lung surfactant
– Cardiolipin is ~15% of PL in cardiomyocytes
what is DPG
The derivative diphosphatidylglycerol
(DPG), also known as cardiolipin, was first
identified in the 1950s, followed by PG and
bis(monoacylglycero)phosphate
where is cadiolipin found
Cardiolipin is found in all tissues, but it is
highly abundant in cardiomyocytes (~15%
of total PL)
what is used to make cardiolipin
most of PG
what is PG
phosphatidulglycerol
where is cardiolipin synthase found
Cardiolipin synthase is exclusively found in
the mitochondrial matrix
– …and so is cardiolipin
what are the functinos of cardiolipin
-required as a structual component
-cardiolipin is an initiator of cell death
-acts as an anticoagulant when found in plasma
cardiolipin as a structural component
Cardiolipin is required as a structural
component to hold together complexes III,
IV, and V of the electron transport system
within mitochondria
cardiolipin as an initiator of cell death
Cardiolipin is an initiator of cell death: its
oxidation ‘flips’ cardiolipin from the inner
mitochondrial membrane to the outer
membrane, leading to the release of Cyt-c
from complex IV
– Raises cytosolic [Ca ++ ]
cardiolipin as an anticoagulant
Acts as an anticoagulant when found in
plasma
– Since cardiolipin is foreign to the bloodsteam,
antibodies are generated
– Titers of antibodies against cardiolipin are
directly associated with lupus
Cardiolipin and Barth syndrome
Injections of cardiolipin alleviate the
disease symptoms
how is cardiolipin remodelled
- Cardiolipin is usually remodeled by the
removal of a fatty acid by a PLA 2, and the
re-addition of a fatty acid (almost always
linoleate) by an enzyme known as tafazzin - Tafazzin is a phospholipid transacylase
what is barth syndrome
- Barth syndrome is a rare X-chromosome
linked disorder leading to dysfunctional
tafazzin, characterized by cardiomyopathy,
growth retardation, and infantile death - At the cellular and biochemical levels,
mitochondria are deformed and exhibit
very low ATP generation, a decrease of
cardiolipin, and an accumulation of lyso-
DPG
