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Metabolism of Sphingolipids

Sphingophospholipids

Glycosphingolipids

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

Sphingosine; Amino Alchol

Sphingosine; Amino Alchol
Sphingosine; Amino Alchol

Sphingosine; Amino Alchol

Sphingosine; Amino Alchol HO- C H- C H= C H-( C H 2 ) 1 2

HO-CH-CH=CH-(CH 2 ) 12 CH 3

CH-NH 2

I

CH 2 -OH

Ceramide is Produced by Linking Fatty Acid to Sphingosine

HO-CH-CH=CH-(CH 2 ) 12 CH 3

O

CH-NH-C-(CH 2 ) n

I

-CH 3

CH 2 -OH

Sphingomyelin is Phosphocholine Ester of Ceramide HO-CH-CH=CH-(CH O ║ 2 ) 12 CH 3 CH-NH-C-(CH
Sphingomyelin is Phosphocholine
Ester of Ceramide
HO-CH-CH=CH-(CH
O ║
2 ) 12 CH 3
CH-NH-C-(CH
-CH 3
2
) n
I
+
CH 2 -O
P
-CH
-CH 2 -N(CH 3 ) 3
2
FATTYACID G L Y C FATTYACID E R O L PHOSPHATE ALCOHOL PHOSPHOACYLGLYCEROL
FATTYACID
G
L
Y
C
FATTYACID
E
R
O
L
PHOSPHATE
ALCOHOL
PHOSPHOACYLGLYCEROL
FATTYACID G L Y C FATTYACID E R O L PHOSPHATE ALCOHOL PHOSPHOACYLGLYCEROL Sphingophospholipids

Sphingophospholipids

4
4
+ CO 2

+ CO 2

+ CO 2 5

Transfer Of Phosphocholine to Ceramide

Produces

Sphingomylein

Ceramide

Phosphocholine to Ceramide Produces Sphingomylein Ceramide S p h i n g o m y l
Phosphocholine to Ceramide Produces Sphingomylein Ceramide S p h i n g o m y l

Sphingomylein

Phospatidyl Choline

Diacyl Glycerol

Produces Sphingomylein Ceramide S p h i n g o m y l e i n

Ceramide is Produced by Linking Fatty Acid to Sphingosine

HO-CH-CH=CH-(CH 2 ) 12 CH 3

CH-NH

I

O

-C-(CH 2 2 ) n -CH 3

CH 2 -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)

N - A cetyl n euraminic A cid ( NANA )
N - A cetyl n euraminic A cid ( NANA ) 8
Galactocerbroside Gluco cerbroside 9
Galactocerbroside
Galactocerbroside
Galactocerbroside Gluco cerbroside

Glucocerbroside

Activated Donors in Glycolipids Synthesis

• UDP-Glucose

• UDP-Galactose

• UDP-N-Acetylgaalctoseamine

• CMP- N-Acetylneuraminic Acid

Synthesis • UDP- Glucose • UDP- Galactose • UDP- N-Acetylgaalctoseamine • CMP- N-Acetylneuraminic Acid 10

Transfer of Sulfate Group to Galactocerbroside Produces Sulfogalatocerbroside (Sulfatide)

Transfer of Sulfate Group to Galactocerbroside Produces Sulfogalatocerbroside (Sulfatide)

Sulfate Group Donor

Sulfate Group Donor 3 P hospho a denosine 5 P hospho s ulfate PAPS

3 Phosphoadenosine 5 Phosphosulfate

PAPS

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

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 NAcGal Gal NANA Cer
Glc
Gal
NAcGal
Gal
NANA
Cer
Glc Gal NAcGal NANA Cer
Glc
Gal
NAcGal
NANA
Cer
Glc Gal Cer NANA
Glc
Gal
Cer
NANA
Glc Gal Cer
Glc
Gal
Cer

βGalactosidase

βHexoseaminidase

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.

Degradation of Sphingomyelin

Sphingomyelin

Degradation of Sphingomyelin Sphingomyelin Ceramide S p h i n g o s i n e

Ceramide

Degradation of Sphingomyelin Sphingomyelin Ceramide S p h i n g o s i n e

Sphingosine

Sphingomyelinase

Ceramidase

of Sphingomyelin Sphingomyelin Ceramide S p h i n g o s i n e Sphingomyelinase