metabolism of sphingolipids - ju medicine...sphingolipidoses • lipid storage diseases • defect...
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Metabolism of SphingolipidsSphingophospholipids
Glycosphingolipids
Faisal Khatib MD; PhD
Faculty of Medicine, University of Jordan
Sphingosine; Amino Alchol
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Sphingosine; Amino Alchol
HO-CH-CH=CH-(CH2)12CH3
CH-NH2ICH2-OH
Ceramide: Fatty Acid to joined to Sphingosine
HO-CH-CH=CH-(CH2)12CH3O║
CH-NH-C-(CH2)n-CH3ICH2-OH
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Sphingomyelin is Phosphocholine Ester of Ceramide
HO-CH-CH=CH-(CH2)12CH3O║
CH-NH-C-(CH2)n-CH3ICH2-O -CH2-CH2-N(CH3)3
+P
GLYCEROL
FATTY ACID
FATTY ACID
PHOSPHOACYLGLYCEROL
PHOSPHATE
ALCOHOL
Sphingophospholipids
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+ CO2
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Transfer Of Phosphocholine to Ceramide Produces
Ceramide Phosphatidyl Choline
Sphingomylein Diacyl Glycerol
Sphingomylein
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Glycolipids are Formed by Linking one or More Sugars to Ceramide
Ceramide +
-Glucose or Galactose => Cerebroside
-Sulfated Galactose => Sulfoglycosphingolipids
-Oligosaccharide => Globoside
-Oligosaccharide with NANA => Gangliosides
N-Acetylneuraminic Acid (NANA)
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Activated Donors in Glycolipids Synthesis
• UDP-Glucose
• UDP-Galactose
• UDP-N-Acetylgalctoseamine
• CMP- N-Acetylneuraminic Acid
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Galactocerbroside
Glucocerbroside
Transfer of Sulfate Group to Galactocerbroside Produces Sulfogalatocerbroside (Sulfatide)
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3 Phosphoadenosine 5 Phosphosulfate PAPS
Sulfate Group Donor
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Degradation of Sphingolipids• Hydrolytic Enzymes, Specific for the Sugar• - α Galactosidase
- β Galactosidase- neuraminidase- Hexoaminidase
• In Lysosomes• Enzymes are firmly Bound to Lysosomal
Membrane. • The pH Optimum 3.5-5.5• Stepwise Sequential Process• “Last on, First off”
Glc Gal
Gal
GalNAcGal
NAcGal
NANA
NANA
NANA
Glc
Glc Gal
Glc Gal
βGalactosidase
βHexoseaminidase
neuraminidase
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Sphingolipidoses
• Lipid Storage Diseases
• Defect in one of the Enzyme
• Inherited as Autosomal RecessiveDisease
• Accumalation of Specific Lipid
Substrate of the Defective Enzyme
• Brain is Mostly Affected.
• Extent of Enzyme deficiency is the same in Different Tissues.
Degradation of Sphingomyelin
Sphingomyelin
Ceramide
SphingosineSphingomyelinase
Ceramidase
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