Download Objectives 27 - u.arizona.edu

Summary of key points:
• dipalmitoyl lecithin is the major component of lung surfactant
• surfactant separates water layers of alveolus by breaking the surface tension and requires L:S
(lecithin:sphingomyelin) ratio of 2.0 or greater
• L:S ratio less than 2.0 leads to RDS
• phosphatidylinositol anchors glycoproteins to plasma membrane
• cardiolipin in mitochondrial inner membrane aids function of phosphate transporter and
cytochrome
oxidase
• plasmalogens are lost in multiple sclerosis resulting in demyelination
• sphingolipid classes:
o ceramide - core structure
o sphingomyelin - component of erythrocyte and neuronal membranes
o cerebrosides (glycolipid) – important component of the brain; sulfogalactocerebroside in
myelin;
o globosides (glycolipid) – lactosylceramide in erythrocyte membrane
o gangliosides (glycolipid) –mainly in ganglions
• GM1 ganglioside receptor binds cholera toxin facilitating its uptake by intestinal mucosa cells
• carbohydrate structure of glycolipids on red blood cells distinguishes between types
o O substance is core without modification due to inactive enzymes – universal donor because
lacks
modifications but individuals have antibodies to both A and B
o A substance formed by N-acetylgalactosamine transferase – have antibodies to B only
o B substance formed by galactosyl transferase - have antibodies to A only
o types A and B express both enzymes – universal acceptor because lack antibodies
• Sphingolipidoses
o Fabry's disease: accumulates ceramide trihexoside
o Gaucher’s disease: accumulates glucocerebroside; hepato-splenomegaly
o Krabbe's disease: accumulates galactocerebroside; demyelination
o Niemann-Pick (Types A,B) disease: accumulates sphingomyelin; hepato-splenomegaly
o Tay-Sachs disease: accumulates GM2; blindness; cherry red spot
o Sandhoff's disease: accumulates GM2 and globoside; blindness; cherry red spot
Phosphoglycerides

Most phospholipids have a glycerol backbone. Include Phospholipids include: 1)
phosphatidic acid, 2) phosphatidylcholine,3) phosphatidylethanolamine, 4)
phosphatidylinositol, 5) phosphatidylserine, 6) plasmalogens,and 7) sphingomyelin.

Sphingomyelin backbone is made from sphingosine

Phosphoglycerides 2 fatty acyl groups at C1 and C2, lysophospolipids has one acyl
group
1. Identify the major component of lung surfactant, the mechanism by which it works, and its
relationship to evaluating and treating respiratory distress syndrome.

Lecithin is synthesized primarily by addition of choline to diacylglycerol

Lecithin is the most abundant phospholipids found in cell membranes. It also contains a
large portion of the bodys pool of choline which plays a role in nerve transmission

Dipalmitoyl lecithin is >80% component of lung surfactant. Type II epithelial cells
produce it breaks surface tension

Maturity of the lung prior to birth is estimated by the ratio of lethithin to sphingomyelin
L:S in amino fluid. At about 31 weeks the L:S ratio rises sharply to about 2 or greater

Preterm babies have not had enough time to raise the ratio which leads to RDS

RDS→ 40% if ratio of 1.5 to 1.9 75% for ratio less than 1.5
2. Describe the biological roles of phosphatidylinositol and cardiolipin.

phosphatidylinositol, functions as a anchor for glycoproteins to the plasma membrane

CDP-DAG is also for the synthesis of cardiolipin which is found exclusively in
mitochondrial membranes. It is essential for the functioning of cytochrome oxidase and
the phosphate transporter in the mitochondrial inner membrane, therby facilitating
oxidative phophorylation
3. Discuss the relationship of plasmalogens to multiple sclerosis.

Peroxisomes are the primary site for synthesis of glycerol ether phospholipids

The pathway begins with dihydroxyacetone phosphate → glycolytic intermediate

Plasmalogens product of this pathway comprise much of phospholipids of mitochondrial
membrane in nervous tissue & heart

Ethanolamine in myelin & choline in heart as the polar head groups

MS demyleination occurs b/c loss of plasmalogen, as well as sphingolipids from white
matter therefore lipid comp of white matter resembles grey matter

PAF (platelet activating factor) derived from 3-phosphocholine. Facilates platelet
aggregation & mediates other processes such as inflammation and allergic reactions
4. Discuss the significance of GM1 ganglioside receptor in relation to cholera.

Sphingolipids can also contain carbs instead of phosphocholine

3 sphingolipid that contain carb cerebrosides, globosides & gangliosides

Sugars are either neutral or acidic they also impart an overall negative charge on the cell
surface → important for attachment to connective tissue(+) charge

Gangliosides serve to function as cell surface receptors. GM1 is located in the human
intestinal mucosal cells and is a receptor for cholera toxin.

The toxin works by maintaining adenylyl cyclase in an active state causing cyclic AMP, a
hormonal second messenger, to be overproduced leading to excessive secretion of
chloride into the intestinal lumen.
5. Explain the biochemical basis of ABO blood group antigens.
6. Identify the defective enzyme, accumulated sphingolipid and principal symptom associated
with
Fabry's, Gaucher’s, Krabbe's, Niemann-Pick (Type A), Tay-Sachs, and Sandhoff diseases.

Cerebrosides → simplest glycolipid made up of galactose or glucose.
Galactocerebrosides → mostly found in the brain

Glucocerebrosides → located mostly in extraneural tissue found as intermediates
in the synthesis or degradation of globosides or gangliosides

Globosides & Gangliosides are more complex glycolipids both contain poly sacs

Gangliosides contain terminal silic acid residues whereas globsides do not
Disorder
Fabry's
Defective
Sphingo-
Enzyme
lipid
-galactosidase A ceramide
Symptoms
skin rash; kidney failure
disease
trihexoside
Gaucher's glucocerebro-
gluco-
disease
cerebroside of long bones & pelvis; mental
sidase
hepato-splenomegaly; erosion
retardation
Krabbe's
-galactosidase
disease
galacto-
lack of myelin; retardation.
cerebroside Accumulate in the white matter
Niemann- Sphingomyelinase Sphingo-
hepato-splenomegaly;
Pick
myelin
retardation
Sandhoff's hexosaminidase
globoside
symptoms show more rapid
disease
and GM2
progression than Tay-Sachs
disease
A (22) + B
(4)
Tay-Sachs hexosaminidase A GM2
retardation; blindness; red
disease
cherry spot on macula