Exam 4 L4: Spingolipids

Question 1

Sphingolipids are identified structurally by having a core structure of _______ attached to either phosphocholine (called ______) or sugars (called ________)

Gangliosides are basically glycosphingolipids with an acidic _____

Answer 1

Spingolipids are identified structurally by having a core structure of ceramide attached to either phosphocholine (called sphingomyelin) or sugars (called glycosphingolipids).

Gangliosides are glycosphingolipids with an attached salic acid.

Question 2

Sphingolipids are located in the ___________

Answer 2

Sphingolipids are located in the plasma membrane

Question 3

The most simple sphingolipid is _______

Answer 3

Sphingosine

Question 4

What is the fundamental structural unit common to all sphingolipids?

What is it composed of?

What are the three main types of sphingolipids?

Answer 4

Fundamental structural unit common to all sphingolipids is ceramide

Ceramide is composed of sphingosine and a fatty acid

Three main types of sphingolipids:

1. Sphingomyelins
2. Glycosphingolipids
3. Gangliosides

Question 5

Explain the structures of the following:
Spingosine

Ceramide

Sphingomyelin

Answer 5

Spingosine is most basic sphingolipid

Ceramide has a spingoside backbone with a fatty acid reside

Sphingomyelin has ceramide and a phosphocholine group

Question 6

How many sugars does a cerebroside have?

What about a ganglioside?

Answer 6

Cerebroside has 1 sugar

Ganglioside has more than one sugar plus sialic acid

Question 7

What is important in blood typing?

Answer 7

Blood Typing: Cerebroside

Question 8

______ the backbone for spingolipids has a long alkyl group connected at C1, and a free amine at C2, as a backbone

Answer 8

Spingosine, the backbone for spingolipids, has a long alkyl group connected at C1, and a free amine at C2

Question 9

Sphingolipids occur in the _____ and ____ of nearly all cells

The highest concentration of sphingolipids is found in the _________

Answer 9

Sphingolipids occur in the blood and plasma membrane of nearly all cells

The highest concentration of sphingolipids is found in the white matter of the central nervous system

Question 10

What are the precursors of sphingolipids?

What enzyme takes those precursors and starts making them into sphingolipids?

What is the cofactor of that enzyme

Answer 10

Precursors of Sphingolipids: Serine and Palmityl CoA

Condensation of serine and palmitoyl coA is catalyzed by Serine palmitoyltransferase

Cofactor is pyridoxal phosphate

Question 11

De novo synthesis of ceramide occurs in the ____

It is then transported to the ____- where it can be further metabolized to other sphingolipids

Where does it get degraded?

Answer 11

Ceramide synthesis occurs in the ER

It is then transported to the golgi where it can be turned into other sphingolipids

It is degraded by lysozomes

Question 12

Sphingolipids are commonly believed to protect the cell surface against harmful enviornmental factors by forming a _________ & ______outer leaflet of the plasma membrane lipid bilayer.

Sphingolipids are important in cell recognition and signal ___________

Sphingolipids form the myelin sheath around the nerves in the CNS. The highest concentration are found in the __________.

Answer 12

Sphingolipids are commonly believed to protect the cell surface against harmful enviornmental factors by forming a mechanically stable and chemically resistant outer leaflet of the pm lipid bilayer.

Sphingolipids are important in cell recognition and signal transmission/transduction.

Sphingolipids form the myelin sheath around the nerves in the CNS. The highest concentration are found in the white matter of the CNS.

Question 13

Both _____ & _____ are important in second messenger systems

Explain what they both do

Answer 13

Ceramide and sphingosine are important in second messenger systems

Ceramide is a second messenger for apoptosis

Sphingosine is an inhibitor of protein kinase C

Question 14

Some of the most devastating inborn errors in metabolism are those associated with defects in the enzymes responsible for the __________ which are particularly abundant in the membranes of neural cells

Many of these disorders lead to ___________

Answer 14

Some of the most devastating inborn errors in metabolism are those associated with defects in the enzymes responsible for the lysosomal degradation of membrane glycosphingolipids, which are particularly abundant in the membrane of neural cells

Many of these disorders lead to severe psychomotor retardation and early lethality.

Question 15

What is another name of Sphingolipid Storage Diseases?

Answer 15

“Sphingolipidoses” means sphingolipid storage disease

Question 16

For each sphingolipidose, explain the messed up enzyme and what lipid that accumulates:

1. Tay-Sachs
2. Gaucher’s Disease
3. Faubry’s Disease
4. NiemannPick Disease

Answer 16

1. Tay Sachs: deficient Hexosaminidase A, accumulation of Ganglioside GM2

2. Gaucher’s Disease: Deficient Glucocerebrosidase, accumulation of glucocerebroside
3. Fabry’s Disease: defective a-Galactosidase A, accumulation of ceremide trihexoside
4. Niemann Pick: deficient sphingomyelinase, accumulation of sphingomeylin

Question 17

Sphingolipids are degraded within ______

Important features of the catabolic pathway are:

• all the rxn occur within the ___
• the enzymes are ____

Due to genetic error, the substrate for that enzyme accumulates and is deposited within the lysosome of the tissue. These disorders are called _____

Answer 17

Sphingolipids are degraded within lysosomes

• All rxn occur within lysosomes
• All of the enzymes are hydrolases

Due to genetic error, substrate for the enzyme accumulates and is deposited within the lysosome of the tissue. These disorders are called sphingolipidoses

Question 18

Top Hat Questions:

Lysosomal storage diseases are most of the time due to defects in……

The heaviest sphingolipid is…..

Ceramide structure can be found in….

Answer 18

Lysosomal storage diseases are most of the time due to defects in the lysosomal degradation enzyme

The heaviest sphingolipid is ganglioside

Ceramide structure can be found in spingomyelin AND glycosphingolipid

Question 19

Precursor of prostaglandin is_______

Most important dietary precursor of prostaglandins is _____

Prostaglandings have ____ carbon skeleton and a five member ring and are based upon the fatty acid____

Answer 19

Precursor of prostaglandins: arachidonic acid

Most important dietary precursor of prostaglandins is linoleic acid

Prostaglandins have 20 carbons with a five member ring and are based on the fatty acid arachidonic acid

Question 20

Prostaglandins are _____ and ____ lipid mediators

Answer 20

Autocrine and paracrine

Question 21

What do prostaglandins have to do with inflammation?

Which prostaglandin is important with:

Blood clotting?

Child labor?

Answer 21

Prostaglandins are natural mediations of inflammation

Thromboxane stimulates constriction and clotting of plateles

Child Labor: PGE2

Question 22

Aspirin blocks an enzyme called ______

By inhibiting this enzyme, the synthesis of prostaglaninds is ______

Answer 22

Aspirin blocks an enzyme called cyclooxygenase, or COX1 and COX2, which add oxygen to arachidonic acid to convert to PGEs.

By inhibiting this enzyme, the synthesis of prostaglandins is blocked, which releaves some of the effects of pain and fever.

Aspirin is also an anti-coagulant because it inhibits prostaglandin synthesis

Question 23

Thromboxane:

The two major thromboxanes are ______ (active) and ______ (inactive)

What is the function of thromboxane?

Effects of aspirin?

Answer 23

Thromboxane:

The two major thromboxanes are Thromboxane A2 (active) and Thromboxane B2 (inactive)

Function: Thromboxane A2 is a vasoconstrictor and facilitates platelet aggregation.

Aspirin prevents the formation of PGEs, therefore preventing the formation of thromboxane A2