PS, PI, and PG synth and fn

Question 1

What does PS mean

Answer 1

phosphatidylserine

Question 2

PS accounts for _ of the total PS in mamalina cells

Answer 2

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

Question 3

what are the precursors for PS synth

Answer 3

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

Question 4

PS synthesis from PC & PE requires

Answer 4

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

Question 5

PSS- phosphatidylserine synthases

how many exist in mammals

Answer 5

Two PSS exist in mammals: PSS1 and
PSS2

Question 6

PSS1 and PSS2 uses

Answer 6

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

Question 7

AA sequences bw PSS1 and PSS2

Answer 7

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

Question 8

where is PSS1 expressed

Answer 8

PSS1 is ubiquitously expressed in vivo

Question 9

where is PSS2 found

Answer 9

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

Question 10

PSS1 knockout mice are

Answer 10

PSS1 knockout mice are viable and they
appear phenotypically norma

Question 11

male PSS2 mice

Answer 11

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

Question 12

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

Answer 12

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

Question 13

The mechanisms that regulate PS synthesis

Answer 13

The mechanisms that regulate PS
synthesis are unknown:

Question 14

DHA and PS

Answer 14

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

Question 15

how does PS relate to PSS1 and PSS2 activities

Answer 15

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

Question 16

what does PS activate

Answer 16

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

Question 17

where is PS found

Answer 17

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

Question 18

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

Answer 18

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

Question 19

PI accounts for _ of the total PL in
mammalian cells

Answer 19

up to 10%

Question 20

how essential is PI

Answer 20

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

Question 21

What is PI

Answer 21

phosphatidylinositol

Question 22

where does inositol come from

Answer 22

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

Question 23

what are the functions of PI

Answer 23

• 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

Question 24

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

Answer 24

<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

Question 25

what is DPG

Answer 25

The derivative diphosphatidylglycerol
(DPG), also known as cardiolipin, was first
identified in the 1950s, followed by PG and
bis(monoacylglycero)phosphate

Question 26

where is cadiolipin found

Answer 26

Cardiolipin is found in all tissues, but it is
highly abundant in cardiomyocytes (~15%
of total PL)

Question 27

what is used to make cardiolipin

Answer 27

most of PG

Question 28

what is PG

Answer 28

phosphatidulglycerol

Question 29

where is cardiolipin synthase found

Answer 29

Cardiolipin synthase is exclusively found in
the mitochondrial matrix
– …and so is cardiolipin

Question 30

what are the functinos of cardiolipin

Answer 30

-required as a structual component
-cardiolipin is an initiator of cell death
-acts as an anticoagulant when found in plasma

Question 31

cardiolipin as a structural component

Answer 31

Cardiolipin is required as a structural
component to hold together complexes III,
IV, and V of the electron transport system
within mitochondria

Question 32

cardiolipin as an initiator of cell death

Answer 32

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 ++ ]

Question 33

cardiolipin as an anticoagulant

Answer 33

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

Question 34

Cardiolipin and Barth syndrome

Answer 34

Injections of cardiolipin alleviate the
disease symptoms

Question 35

how is cardiolipin remodelled

Answer 35

• 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

Question 36

what is barth syndrome

Answer 36

• 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