Biochem- Sphingolipids and Sphingolipidoses Flashcards
What alcohol are sphingolipids derived from?
-Sphingosine and contain ceramide
Wha are the two types of sphingolipids?
Sphingomyelin and Glycosphingolipds
What is the main difference between spingomyelin and glycosphingolipids?
-Sphingomyelin contains no sugar units, glycosphingolipids do
Niemann-Pick disease is characterized by _________________.
-The accumilation of sphingomyelin and cholesterol
What are the four types of Niemann-Pick?
-Type A, B, C, and D
What is defective in both Type A and B Neimann-Pick?
Sphingomyelinase
What is the result of the sphingomyelinase deficiency in Neimann-Pick?
-No sphingomyelin breakdown, and therefore an accumilation of sphingomyelin in the brain, liver and spleen.
What population is at highest risk for Type A Neimann-Pick?
Ashkenazi Jews: severe form–> death within a few years of birth
What distinguishes Type A from Type B?
Type A: <1% Sphingomyelinase activity, early death
Type B: ~10% sphingomyelinase activity, may live to adulthood
What is the main defec in type C and D Neimann-Pick?
-defect in cholesterol transport resulting in accumilation of cholesterol
What are cerebrosides?
-Glycosphingolipids that contain at least one sugar residue (aka ceremide monosaccharides)
Where are cerebrocides particularly prominent?
in the myelin sheath
What are the two mst important cerebrocides?
Galactocerebrocide
Glucocerebrocide
A deficiency of what enzyme will cause an accumilation of glucocerebroside?
-ß-glucosidase
What diesase is characterized by a deficiency of ß-glucosidase?
Gaucher disease
Where does glucocerebroside accumilate in Gaucher disease?
Bone Marrow, liver and spleen (Gaucher cells)
What are the three types of gaucher disease?
Type 1: Chronic non-neuropathic
Type 2: Acute neuropathic
Type 3: subacute neuropathic
Which of the gaucher disease types is most severe? How about the most mild?
- Type 2 is the most sever and affects the brain the most (death withen the first 2 years of life)
- Type 1 is the most mild
Which gaucher disease ype is the most common? Which ones are treatable?
- Type 1 (chronic non-neuropathic) is the most common.
- Type1 and Type3 are both treatable with enzyme replacement therapy
What is Krabb disease?
an accumilation of galactocerebroside caused by a deficiency of ß-galactosidase
What is a characteristic accumilation in Krabb disease?
-Accumilations of macrophages around blood vesels call globoid cells
Is there demyelination in Krabb disease?
Yes
What disease is characterized by a deficiency of alpha-galactosidase?
-Fabry disease
What accumilates due to a deficiency of alpha-galactosidase?
Ceremide trihexoside
What is sulphatide?
-a galactocerebroside with a sulfate moiety attached
(ß-sulphogalactocerebroside)
If there is a lack of brakdown of sulftide by lysosomal sulphatase, what disease results?
Metachromatic leukodystrophy
What accumilates in Tay-Sachs disease?
-Ganglioside GM2
What enzyme is deficient in Tay-Sachs?
Hexosamidase A
What is the mode of inheritance of all of these sphingolipidoses? Which one is the only exception?
- Autosomal recessive
- Fabry’s which is X-linked
What are currently the only treatable sphingolipidoses?
-Gaucher disease and fabry disease
What is the most prevelent sphingolipidosis?
-Gaucher followed by Tay-Sachs
