PS, PI, and PG synth and fn Flashcards

1
Q

What does PS mean

A

phosphatidylserine

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2
Q

PS accounts for _ of the total PS in mamalina cells

A

PS accounts for 3-10% of the total PL in
mammalian cells
– PC (60-85%); PE (10-30%)

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3
Q

what are the precursors for PS synth

A

In mammals, PC & PE are the precursors
for PS synthesis

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4
Q

PS synthesis from PC & PE requires

A

PS synthesis from PC & PE requires Ca ++
and phosphatidylserine synthase (PSS)

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5
Q

PSS- phosphatidylserine synthases

how many exist in mammals

A

Two PSS exist in mammals: PSS1 and
PSS2

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6
Q

PSS1 and PSS2 uses

A

PSS1
uses only PC for PS synthesis, and that
PSS2 uses only PE for PS synthesis

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7
Q

AA sequences bw PSS1 and PSS2

A

The amino acid sequences between PSS1
and PSS2 are 30% identical, but little is
known about their protein structures and
how they function

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8
Q

where is PSS1 expressed

A

PSS1 is ubiquitously expressed in vivo

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9
Q

where is PSS2 found

A

PSS2 is in most PSS1 tissues but highly
expressed in Sertoli cells within testes

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10
Q

PSS1 knockout mice are

A

PSS1 knockout mice are viable and they
appear phenotypically norma

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11
Q

male PSS2 mice

A

Male PSS2 knockout mice have smaller
testes and up to half are infertile

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12
Q

However, tissue levels of PC, PS, and PE in the PSS2 knockout tissues

A

However, tissue levels of PC, PS, and PE
in the PSS2 knockout tissues are normal

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13
Q

The mechanisms that regulate PS synthesis

A

The mechanisms that regulate PS
synthesis are unknown:

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14
Q

DHA and PS

A

DHA (22:6n-3) is highly incorporated into PS
within the brain… DHA deficiency reduces
neuronal PS levels

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15
Q

how does PS relate to PSS1 and PSS2 activities

A

PS appears to directly regulate the enzyme
activities of PSS1 and PSS2:
* high levels of PS reduce the rate of PS synthesis

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16
Q

what does PS activate

A

PS is required to activate several intracellular molecules
– ie. protein kinase C, sphingomyelinase, and
Na+ /K+ ATPase

17
Q

where is PS found

A

PS is typically found intracellularly and on
the inner leaflet of cell membranes

18
Q

what is the purpose of PS being on theouter cell membrane leaflet

A

Exposure of PS on the outer cell membrane
leaflet is a marker of cell apoptosis that is
recognized by macrophages (that engulf the
cell)

19
Q

PI accounts for _ of the total PL in
mammalian cells

20
Q

how essential is PI

A

PI is essential for all species
– ie. Deletion of PI synthase in yeast is lethal

21
Q

What is PI

A

phosphatidylinositol

22
Q

where does inositol come from

A

Inositol comes from either diet or de novo synthesis
– Inositol is synthesized from glucose-6- phosphate

23
Q

what are the functions of PI

A
  • 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
24
Q

PG and its derivatives account for _ of
the total PL in most mammalian cells

A

<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

25
what is DPG
The derivative diphosphatidylglycerol (DPG), also known as cardiolipin, was first identified in the 1950s, followed by PG and bis(monoacylglycero)phosphate
26
where is cadiolipin found
Cardiolipin is found in all tissues, but it is highly abundant in cardiomyocytes (~15% of total PL)
27
what is used to make cardiolipin
most of PG
28
what is PG
phosphatidulglycerol
29
where is cardiolipin synthase found
Cardiolipin synthase is exclusively found in the mitochondrial matrix – ...and so is cardiolipin
30
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
31
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
32
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 ++ ]
33
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
34
Cardiolipin and Barth syndrome
Injections of cardiolipin alleviate the disease symptoms
35
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
36
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
37