intro to sphignolipids and lipid rafts

Question 1

how do sphignolipids differ from phospholipids

Answer 1

they dont have a glycerol backbone

Question 2

how are sphignolipids similar to phospholipids

Answer 2

theyy have a polar head group and two non polar tails

Question 3

what are the functions of sphignolipids

Answer 3

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

Question 4

how many classes of sphignolipids are there in mammals

Answer 4

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

Question 5

what are lipid rafts

Answer 5

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

Question 6

what is sphignosine

Answer 6

it is the core moleculle for all sphignolipids analagous to glycerol

Question 7

how is sphignosine synthesized

Answer 7

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

Question 8

how are sphignoid bases synthesized

Answer 8

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

Question 9

how are ceramides synthesized

Answer 9

During the synthesis of sphingosine,
ceramides are synthesized via
dihydrosphingosine

Question 10

how many caramide synthases are there

Answer 10

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

Question 11

what differentiates ceramide synthases

Answer 11

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

Question 12

CerS1

Answer 12

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

Question 13

cerS2

Answer 13

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

Question 14

cers3

Answer 14

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

Question 15

cers4

Answer 15

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

Question 16

cers5

Answer 16

CerS5: palmitoyl-CoA; ubiquitous

Question 17

cers6

Answer 17

CerS6: myristoyl-CoA and palmitoyl-CoA;
ubiquitous

Question 18

why are ceramides good for skin

Answer 18

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

Question 19

where are ceramides found in cell membranes

Answer 19

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

Question 20

what are some of the minute but important functions of ceramides

Answer 20

– 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)

Question 21

what are sphignomyelinis derived from

Answer 21

SM are dervied from ceramides

Question 22

what are sphignomyelins and what type of molecule are they

Answer 22

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

Question 23

SM proportion of sphingolipids in mammales

Answer 23

80%

Question 24

what are the functions of sphingolipids

Answer 24

• 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

Question 25

what are the components in the sphingolipid rheostat

Answer 25

Sphingosine acts as an intermediate in the
balance between ceramides and
sphingosine-1-phosphate

Question 26

what are the functinos of sphingosine-1-phosphate

Answer 26

Sphingosine-1-phosphate opposes some
of the roles of ceramides:
– Inhibition of apoptosis
– Increases cell proliferation

Question 27

what happens when Sphingosine-1-phosphate > ceramides

Answer 27

Observed in proliferation and metastasis of various cancers
* Short chained (C2, C6, and C8) ceramides are in
trials to treat select cancers

Question 28

what happens wen Ceramides > sphingosine1-phosphate

Answer 28

– Observed in cystic fibrosis
– Observed in irritable bowel syndrome

Question 29

what are some functions of ceramide-1-phosphates

Answer 29

• 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

Question 30

what is the structure of complex sphingolipids

Answer 30

Complex sphingolipids contain a ceramide
or dihydroceramide backbone with
carbohydrate chains linked to carbon #1 of sphingosine

Question 31

Glycosphingolipids (or glycolipids) derived
from ceramides include:

Answer 31

Cerebrosides, lactosides, sulfatides,
globosides, gangliosides

Question 32

what are cerebrosides

Answer 32

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

Question 33

how are cerebrosides made

Answer 33

Galactose or glucose, linked to uridine
diphosphate (UDP), are enzymatically
transferred to ceramide, while leaving
behind UDP

Question 34

what are cerebrosides made of

Answer 34

Cerebrosides are the precursors for much
more complex sphingolipids
– Primarily derived from glucocerebrosides

Question 35

functions of complex sphingolipids

Answer 35

Complex sphingolipids have a variety of
functions
– Primarily they act as molecules to recognize
(or be recognized by) extracellular proteins
and cells