SHINGOLIPIDS/ SHINGOPHOSPHOLIPIDS METABOLISM

Role of sphingolipids Abundant component of myelin sheath (25% in humans) These lipids are in a continuous state of turnover, defects in this metabolism leads to various diseases

SPHINGOLIPIDS AT CELL SURFACES ARE SITES OF BIOLOGICAL RECOGNITION 1. In humans at least 60 different sphingolipids have been identified. 2. Very prominent in neuronal plasma membranes. 3. Carbohydrate moieties of sphingolipids define the human blood groups. 4. The kinds and amounts of gangliosides vary dramatically during development.

Sphingolipids Sphingomyelin contains sphingosine with a long-chain fatty acid attached in amide linkage ( = ceramide) Ceramide plus a phosphocholine group constitutes a sphingomyelin Ceramide is also the core component of glycosphingolipids

. The backbone of sphingomyelin is the amino alcohol sphingosine, rather than glycerol (Figure 17.4). A long-chain fatty acid is attached to the amino group of sphingosine through an amide linkage, producing a ceramide .The alcohol group at carbon 1 of sphingosine is esterified to phosphorylcholine, producing SPHINGOMYELIN

SIMILARITIES BETWEEN PHOSPHATIDYL CHOLINE (A GLYCEROPHOSPHOLID) AND SPHINGOMYELIN (A SPHINGOLIPID) choline choline Overall structure is very similar. Prominent in myelin sheath that surrounds and insulates neurons

SPHINGOMYELIN Sphingomyelin is present in plasma membranes and in lipoproteins It is very abundant in myelin Sphingomyelin is abundant in specialized plasma membrane microdomains called LIPID RAFTS

LIPID RAFTS Lipid rafts are specialized microdomains in the plasma membrane that are rich in sphingomyelin and cholesterol Lipid rafts appear to function in signaling

The 3-carbon backbone is analogous to the SPHINGOLIPIDS SPHINGOSINE: a long-chain, unsaturated amino alcohol, a major constituent of sphingolipids, including sphingomyelins. The 3-carbon backbone is analogous to the 3-carbons of glycerol. At C3 there is the long chain amino alcohol sphingosine.

SPHINGOLIPIDS At C2 there is a fatty acid which is usually saturated or monounsaturated, and can be either 16,18, 22, or 24 carbons long.

SPHINGOLIPIDS Ceramide is the parent compound. Other polar head groups can be attached at position X.

SPHINGOLIPIDS Glycosphingolipids are a sub-group of sphingolipids that contain sachharide headgroups

Glucosyl-ceramide / Glucocerebroside Monohexoside Glu Ceramide Dihexoside Gal Glu Ceramide Trihexoside Gal Gal Glu Ceramide Biosynthesis of membrane lipids and steroids 1

Galactosyl – ceramide / Galactocerebroside Monohexoside Gal Ceramid Dihexozid Gal Gal Ceramid Biosynthesis of membrane lipids and steroids 1

Biosynthesis of membrane lipids and steroids 1 ABO blood group system Glu Gal GalNAc Gal „O” (H) antigen Fuc Glu Gal GalNAc Gal GalNAc „A” antigen Fuc Glu Gal GalNAc Gal Gal „B” antigen Fuc Biosynthesis of membrane lipids and steroids 1

Biosynthesis of membrane lipids and steroids 1 Gangliosides Glu GM3 Gal Ceramide NANA GM2 GalNAc Gal Glu Ceramide NANA GM1 GalNAc Gal Glu Ceramide Cholera toxin Gal NANA Biosynthesis of membrane lipids and steroids 1