SHINGOLIPIDS SHINGOPHOSPHOLIPIDS METABOLISM Role of sphingolipids Abundant component

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 longchain 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 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

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 C 3 there is the long chain amino alcohol sphingosine.

SPHINGOLIPIDS At C 2 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 Dihexoside Trihexoside Gal Glu Ceramide Biosynthesis of membrane lipids and steroids 1 15

Galactosyl – ceramide / Galactocerebroside Monohexoside Dihexozid Gal Biosynthesis of membrane lipids and steroids 1 Gal Ceramid 16

ABO blood group system Glu Gal. NAc Gal „O” (H) antigen Fuc Glu Gal Gal. NAc „A” antigen Gal „B” antigen Fuc Glu Gal. NAc Gal Fuc Biosynthesis of membrane lipids and steroids 1 17

Gangliosides GM 3 Gal Glu Ceramide NANA GM 2 Gal. NAc Gal Glu Ceramide NANA GM 1 Gal. NAc Gal Cholera toxin NANA Biosynthesis of membrane lipids and steroids 1 18