Metabolism of Sphingolipids

Sphingophospholipids Glycosphingolipids
Faisal Khatib MD; PhD Faculty of Medicine, University of Jordan

Sphingosine; Amino Alchol

Sphingosine; Amino Alchol

HO-CH-CH=CH-(CH2)12CH3 CH-NH2 I CH2-OH

Ceramide is Produced by Linking Fatty Acid to Sphingosine

HO-CH-CH=CH-(CH2)12CH3 O CH-NH-C-(CH2)n-CH3 I CH2-OH

Sphingomyelin is Phosphocholine Ester of Ceramide

HO-CH-CH=CH-(CH2)12CH3 O CH-NH-C-(CH2)n-CH3 I CH2-O P -CH2-CH2-N(CH3)3+

F T A ID A TY C

G L Y C E R O L

F T A ID A TY C

P OP A H S H TE

AC H L LOO

P O P O C L LY E O H SH A YG CR L

Sphingophospholipids

+ CO2

Transfer Of Phosphocholine to Ceramide Produces Sphingomylein

Ceramide Phospatidyl Choline

Sphingomylein

Diacyl Glycerol

Ceramide is Produced by Linking Fatty Acid to Sphingosine

HO-CH-CH=CH-(CH2)12CH3 O CH-NH-C-(CH2)n-CH3 2 I CH2-OH

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)

Galactocerbroside

Glucocerbroside

Activated Donors in Glycolipids Synthesis

UDP-Glucose UDP-Galactose UDP-N-Acetylgaalctoseamine CMP- N-Acetylneuraminic Acid

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Transfer of Sulfate Group to Galactocerbroside Produces Sulfogalatocerbroside (Sulfatide)

Sulfate Group Donor

3 Phosphoadenosine 5 Phosphosulfate

PAPS

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Degradation of Sphingolipids
Hydrolytic Enzymes, Specific for the Sugar - Galactosidase - 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

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Ce

Glc

Gal
NANA

NAcGal

Gal

Ce r

Glc

Gal
NANA

NAcGal

Ce r

Glc

Gal
NANA

Galactosidase
Hexoseaminidase

Ce r

Glc

Gal

neuraminidase

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.

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Degradation of Sphingomyelin
Sphingomyelin

Ceramide

Sphingosine

Sphingomyelinase Ceramidase

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