intro to sphignolipids and lipid rafts Flashcards
how do sphignolipids differ from phospholipids
they dont have a glycerol backbone
how are sphignolipids similar to phospholipids
theyy have a polar head group and two non polar tails
what are the functions of sphignolipids
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
how many classes of sphignolipids are there in mammals
In mammals, there are 6 major classes of
sphingolipids and to date 13 diseases
directly associated with sphingolipids
what are lipid rafts
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
what is sphignosine
it is the core moleculle for all sphignolipids analagous to glycerol
how is sphignosine synthesized
It is synthesized, together with other
sphingoid bases (the collective
components of the pathway), along the
cytosolic side of the endoplasmic reticulum membrane
how are sphignoid bases synthesized
The synthesis of sphingoid bases starts
with the condensation of palmitoyl-CoA (or “activated” palmitate) with serine
how are ceramides synthesized
During the synthesis of sphingosine,
ceramides are synthesized via
dihydrosphingosine
how many caramide synthases are there
To date, 6 ceramide synthases (CerS)
have been identified
– CerS1, CerS2… CerS6
what differentiates ceramide synthases
Ceramide synthases exhibit specificities
for fatty acyl chain length and for tissue
distribution
CerS1
CerS1: stearoyl-CoA; brain, skeletal
muscle, testis
cerS2
CerS2: C 20-C26 fatty acyl-CoAs; liver,
kidney
cers3
CerS3: C 22-C26 fatty acyl-CoAs; skin, testis
cers4
CerS4: C 18-C20 fatty acyl-CoAs; ubiquitous
cers5
CerS5: palmitoyl-CoA; ubiquitous
cers6
CerS6: myristoyl-CoA and palmitoyl-CoA;
ubiquitous
why are ceramides good for skin
- Ceramides are extremely water insoluble
and this property primarily provides the
water barrier for skin
– 1/3 of total lipids in skin are ceramides
where are ceramides found in cell membranes
In cell membranes, ceramides localize in
rafts and also influence membrane
curvature
what are some of the minute but important functions of ceramides
– 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)
what are sphignomyelinis derived from
SM are dervied from ceramides
what are sphignomyelins and what type of molecule are they
While also sphingolipids, SMs belong to a
unique class of PLs that is not derived with
a glycerol backbone
SM proportion of sphingolipids in mammales
80%
what are the functions of sphingolipids
- 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
what are the components in the sphingolipid rheostat
Sphingosine acts as an intermediate in the
balance between ceramides and
sphingosine-1-phosphate
what are the functinos of sphingosine-1-phosphate
Sphingosine-1-phosphate opposes some
of the roles of ceramides:
– Inhibition of apoptosis
– Increases cell proliferation
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
what happens wen Ceramides > sphingosine1-phosphate
– Observed in cystic fibrosis
– Observed in irritable bowel syndrome
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
what is the structure of complex sphingolipids
Complex sphingolipids contain a ceramide
or dihydroceramide backbone with
carbohydrate chains linked to carbon #1 of sphingosine
Glycosphingolipids (or glycolipids) derived
from ceramides include:
Cerebrosides, lactosides, sulfatides,
globosides, gangliosides
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
how are cerebrosides made
Galactose or glucose, linked to uridine
diphosphate (UDP), are enzymatically
transferred to ceramide, while leaving
behind UDP
what are cerebrosides made of
Cerebrosides are the precursors for much
more complex sphingolipids
– Primarily derived from glucocerebrosides
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
