intro to sphignolipids and lipid rafts Flashcards

(36 cards)

1
Q

how do sphignolipids differ from phospholipids

A

they dont have a glycerol backbone

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2
Q

how are sphignolipids similar to phospholipids

A

theyy have a polar head group and two non polar tails

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3
Q

what are the functions of sphignolipids

A

They are essential structural components
of all cell membranes, and many act as
modulators of cell signaling, cell adhesion,
and as components of protective antigens

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4
Q

how many classes of sphignolipids are there in mammals

A

In mammals, there are 6 major classes of
sphingolipids and to date 13 diseases
directly associated with sphingolipids

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5
Q

what are lipid rafts

A

they are when sphignolipids aggregate together with cholesterol in small compact disctint regions on cell membranes that tend to be “detergent insouble”

-they provide platforms on cell membranes for various biological functions
-they rapidly assemble and dissasemble due to several biophysiological factors

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6
Q

what is sphignosine

A

it is the core moleculle for all sphignolipids analagous to glycerol

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7
Q

how is sphignosine synthesized

A

It is synthesized, together with other
sphingoid bases (the collective
components of the pathway), along the
cytosolic side of the endoplasmic reticulum membrane

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8
Q

how are sphignoid bases synthesized

A

The synthesis of sphingoid bases starts
with the condensation of palmitoyl-CoA (or “activated” palmitate) with serine

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9
Q

how are ceramides synthesized

A

During the synthesis of sphingosine,
ceramides are synthesized via
dihydrosphingosine

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10
Q

how many caramide synthases are there

A

To date, 6 ceramide synthases (CerS)
have been identified
– CerS1, CerS2… CerS6

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11
Q

what differentiates ceramide synthases

A

Ceramide synthases exhibit specificities
for fatty acyl chain length and for tissue
distribution

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12
Q

CerS1

A

CerS1: stearoyl-CoA; brain, skeletal
muscle, testis

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13
Q

cerS2

A

CerS2: C 20-C26 fatty acyl-CoAs; liver,
kidney

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14
Q

cers3

A

CerS3: C 22-C26 fatty acyl-CoAs; skin, testis

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15
Q

cers4

A

CerS4: C 18-C20 fatty acyl-CoAs; ubiquitous

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16
Q

cers5

A

CerS5: palmitoyl-CoA; ubiquitous

17
Q

cers6

A

CerS6: myristoyl-CoA and palmitoyl-CoA;
ubiquitous

18
Q

why are ceramides good for skin

A
  • Ceramides are extremely water insoluble
    and this property primarily provides the
    water barrier for skin
    – 1/3 of total lipids in skin are ceramides
19
Q

where are ceramides found in cell membranes

A

In cell membranes, ceramides localize in
rafts and also influence membrane
curvature

20
Q

what are some of the minute but important functions of ceramides

A

– Directly inhibits protein kinase B (or Akt)
– Inhibits signaling mechanisms for glucose
transporter 4 (GLUT4) translocation
– Limited evidence suggests ceramides act as
intracellular signaling molecules
– Induces inflammatory responses in lung (first
noted in cystic fibrosis)
– Inhibition of cell proliferation
– C18 ceramide levels are linked to increased
apoptosis
* Interestingly, reduced 18:0 ceramide levels are
observed in some types of malignant cancers (due
to a downregulation of CerS1)

21
Q

what are sphignomyelinis derived from

A

SM are dervied from ceramides

22
Q

what are sphignomyelins and what type of molecule are they

A

While also sphingolipids, SMs belong to a
unique class of PLs that is not derived with
a glycerol backbone

23
Q

SM proportion of sphingolipids in mammales

24
Q

what are the functions of sphingolipids

A
  • SMs have a high affinity for cholesterol,
    and together they act as key structural
    components of lipid rafts
  • It exists in the plasma membrane as a
    ‘storage molecule’ for ceramide
  • Acts as a receptor for invading pathogens
    (ie. Helicobactor)
  • SM is also carried by lipoproteins
    – Acts to inhibit Lp oxidation, plus decreased
    SM inversely correlates with atherosclerosis
25
what are the components in the sphingolipid rheostat
Sphingosine acts as an intermediate in the balance between ceramides and sphingosine-1-phosphate
26
what are the functinos of sphingosine-1-phosphate
Sphingosine-1-phosphate opposes some of the roles of ceramides: – Inhibition of apoptosis – Increases cell proliferation
27
what happens when Sphingosine-1-phosphate > ceramides
Observed in proliferation and metastasis of various cancers * Short chained (C2, C6, and C8) ceramides are in trials to treat select cancers
28
what happens wen Ceramides > sphingosine1-phosphate
– Observed in cystic fibrosis – Observed in irritable bowel syndrome
29
what are some functions of ceramide-1-phosphates
* Ceramide-1-phosphates, unlike ceramides, have anti-apoptotic functions similar to sphingosine-1-phosphate * Ceramide-1-phosphates uniquely regulate inflammation by directly activating PLA 2 – Thus hydrolysing PLs to release arachidonic acid that can be used to make inflammatory eicosanoids
30
what is the structure of complex sphingolipids
Complex sphingolipids contain a ceramide or dihydroceramide backbone with carbohydrate chains linked to carbon #1 of sphingosine
31
Glycosphingolipids (or glycolipids) derived from ceramides include:
Cerebrosides, lactosides, sulfatides, globosides, gangliosides
32
what are cerebrosides
Cerebrosides are the simplest of the ‘complex sphingolipids’ – Most have a single galactose, and are called galactocerebrosides – Minor are cerebrosides with a single glucose, called glucocerebrosides
33
how are cerebrosides made
Galactose or glucose, linked to uridine diphosphate (UDP), are enzymatically transferred to ceramide, while leaving behind UDP
34
what are cerebrosides made of
Cerebrosides are the precursors for much more complex sphingolipids – Primarily derived from glucocerebrosides
35
functions of complex sphingolipids
Complex sphingolipids have a variety of functions – Primarily they act as molecules to recognize (or be recognized by) extracellular proteins and cells
36