Sphingophospholipid Phospholipids

By: Zelle Humma

PHOSPHOLIPIDS
Two classes of phospholipids:
A.have glycerol (from glucose) as a
backbone 
Glycerophospholipids or
Phosphoglycerides
B.have sphingosine (from serine and
palmitate)  Sphingolipids and
Sphingophospholipids
Both glycerol/sphingo phospholipids
• Structural components of
membranes
• Role in lipid-signaling molecules
All cells except mature RBCs synthesize
phospholipids, whereas triacylglycerol
synthesis occurs only in liver, adipose tissue,
lactating mammaryBy:glands, and intestinal
Zelle Humma
mucosal cells.
A. Glycerophospholipids (Phosphoglycerides
1. Phosphatadic Acid (Precursor)

Glycerophospholipids
are formed from
phosphatidic acid (PA)

Cephalin

Lecithin
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i. Phosphatidyl Choline (PC) / Dipalmitoyl
Phosphatidyl Choline (DPPC) / Di Palmitoyl
Lecithin (DPL)
(Glycerol + 2 FA (Palmitoyl) + P + Choline)
1. PC is exported by liver in the bile and as a
component of plasma lipoproteins
• In liver Phosphatidyl serine (decarboxylation)
Phosphatidyl ethanolamine (methylation)
Phosphatidyl choline
2. Acts as surfactant in lungs
• Surfactant = Complex mixture of lipids (90%) with
DPPC being the major component for reducing
surface tension + Proteins (10%).
• PC surfactant decrease the surface tension of this
alveolar fluid layer  reducing the pressure to
reinflate alveoli  thereby preventing alveolar
collapse (atelectasis)
• Fetal lung maturity can be gauged by determining
the lecithin/sphingomyelin (L/S) ratio in amniotic
fluid  A value ≥2 represents maturity  reflects
the shift from sphingomyelin to PC synthesis that
occurs in pneumocytes at 32 weeks’ gestation.
• Low PC in fetal lungs  Alveolar collapse 
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Respiratory distress syndrome
 Phosphatidyl Choline (PC)
/ Dipalmitoyl
Phosphatidyl Choline
(DPPC) / Di Palmitoyl
Lecithin (DPL)
Glycerol + 2 FA (Palmitoyl) + P
+ Choline
(Pneumocyte I & II)

By: Zelle Humma

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ii. Unusual Phospholipid:
Phosphatidyl Inositol (PI or PIP2)
Glycerol + 2 FA (C1: Stearic acid, C2:
Arachidonic acid) + P + Inositol

Functions:
a. PI acts as reservoir of arachidonic acid in
membranes  Arachidonic acid is substrate
for prostaglandin synthesis

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b. Anchorage of proteins in plasma
membrane mediated by gulosylated
phosphatidyl inositol (GPI)  Glycosyl
phosphatidylinositol anchor protein (GPI-AP)
• GPI-AP on RBCs membrane  Self RBCs 
Immune protection for RBCs
• Lack of GPI-AP on RBC membrane RBCs
destruction by immune (complement)
system
• This GPI-A protein can be cleaved from its
anchor by the action of phospholipase C on
cell membrane

By: Zelle Humma

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c. PIP2 acts as Cell Signaling mediator:
Phosphatidylinositol 4,5 bisphosphate (PIP2) 
Inositol 1,4,5-trisphosphate (IP3) (releases Ca+2) +
diacylglycerol (DAG)  DAG + Ca+2 stimulates
Protein Kinase C  Cellular response

Stearic
Arachidonic
acid
acid
3 2 1

Phospholipase C

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2. Cardiolipin (2 PA esterified with glycerol)
• Found in both Prokaryotes & Eukaryotes
• Found in inner mitochondrial membrane
in eukaryotes  maintenance of
respiratory complexes and ETC
• Cardiolipin is antigenic. A patient infected
with bacterium Treponema pallidum
(causing Syphils) develops antibodies
against bacterial cardiolipin (antigen).
Wasserman Test identifies Anticardiolipin
Antibodies Syphilis diagnosis

Barth syndrome:
•X-linked disorder
•Defect in cardiolipin
remodeling
•Results in
Cardiomyopathy,
muscle weakness,
and neutropenia

Diphosphatidylglycerol
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3. Plasmalogen/Etherphosphoglyceride
Unsaturated Alkyl Group bound with Ether linkage
(Replaces FA at C-1 of glycerol bound with Ester
linkage in glycerophospholipid)

Plasmalogens have
“al” rather than “yl”
in their names.)

Abundant in nerve tissues

Plasmalogen

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Abundant in heart
muscles Phosphatidalcholine
4. Platelet Activating Factor (PAF)
1. Saturated Alkyl Group bound with
Ether linkage (Replaces FA at C-1 of
glycerol bound with Ester linkage in
glycerophospholipid)
2. Acetyl Group bound with Ester linkage
(Replaces FA at C-2 of glycerol bound in
glycerophospholipid)

Ethanolamine

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Functions of Platelet-activating factor (PAF):
•PAF is synthesized by multiple cell types.
•Most potent bioactive molecules known, Effects at
concentrations as low as 10-11 mol/L.)
•Binds to surface receptors, triggering thrombotic
and acute inflammatory events  PAF activates
inflammatory cells and mediates hypersensitivity,
acute inflammatory, and anaphylactic (allergic)
reactions.
•It causes platelets to aggregate and degranulate
•Leads neutrophils and alveolar macrophages to
generate superoxide radicals to kill bacteria.
•Lowers blood pressure

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Degradation of
glycerophospholipids by
phospholipases.

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Overview of sphingolipid synthesis
UDP = uridine diphosphate
CMP = cytidine monophosphate
NANA = N-a ce tylneuraminic acid;
PAPS = 3'-phosphoadenosine-5’phosphosulfate

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B. Sphingolipids (Aminoalcohol
sphingosine)
Types: 1. Sphingophospholipid and
2. Glycosphingolipids / Glycolipids
1. Sphingophospholipid: Sphingomyelin
Sphingosine + FA  Ceramide  + P + Choline
• One and only
SphingoPHOSPHOlipid in body
• Constituent of the myelin
sheath of nerve fibers.
• The myelin sheath is
membranous layer that
insulates and protects neuronal
axons of the central nervous
system [CNS] for rapid neuronal
conduction along axons.

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 (Infantile)

(Non-neuropathic)

•Ashkenazi Jewish population has high frequency of

NP disease
•Mutations in either the NPC1 or NPC2 genes (for
endocytosed cholesterol  both cholesterol and
sphingomyelin accumulation)
By: Zelle Hummaresults in Niemann–
Pick disease Type C [NPC]
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2. Glycolipids / Glycosphingolipids
(Aminoalcohol sphingosine)
Sphingosine + LCFA  Ceramide  +
Sugars (mono/oligosaccharides) 
Glycosphingolipids / Glycolipids
(No Phosphate group)
•Found in nerve tissues
•Found in membranes (outer leaflet of
plasma membrane) of cell  interact
with extracellular environment  Cell
signaling  Cell responses: adhesion
and recognition), growth, and
development
•Membrane glycosphingolipids +
cholesterol + GPI-anchored proteins 
lipid rafts (laterally mobile
microdomains for signaling and
trafficking functions across cell
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membrane)
Glycolipids / Glycosphingolipids
•Show antigenic character (by
carbohydrate portion) for
•ABO blood group antigen
•Embryonic antigen for fetal
development
•Tumor antigen

•Act as cell surface receptors for

cholera and tetanus toxins, viruses and
microbes
•Failure in normal degradation of
glycolipids  Accumulation of
glycolipids in cell  dysregulated
growth in cell

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Glycolipids / Glycosphingolipids
Types: Neutral Glycolipids, Acidic
Glycolipids
i. Neutral Glycolipids (Cerebroside):
Found in peripheral nerves, with high
concentrations in the myelin sheath
Sphingosine + FA
 Ceramide  +
Mono/Oligosacc
harides

By: Zelle Humma

ii. Acidic Glycolipids: Ganglioside
and Sulfatide
• Negatively charged at physiologic pH  N-
acetylneuraminic acid (NANA) a sialic acid in
gangliosides or by sulfate groups in sulfatides.

Neutral Glycolipid

Acidic Glycolipid

By: Zelle Humma

Gangliosides:
Sphingosine + Fatty acid  Ceramide  +
Glucose + Galactose + N-Acetyl
galactosamine + N-Acetyl neuraminic acid
• Found in nerve ending of ganglion cells in CNS

GM2 means
G (for ganglioside) plus a
subscript M, D, T, or Q to
indicate whether there is
one (mono), two (di),
three (tri), or four (quatro)
molecules of NANA in the
ganglioside
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Sulfatides (Sulfoglycosphingolipids):
Galactocerebroside
Sphingosine + Fatty acid  Ceramide  +
Sulfated Galactose
Negatively charged at physiological pH
Found in brain and kidney

Sulfate Donor

By: Zelle Humma

By: Zelle Humma