GLYCOLIPIDS .

Why should I care? Your brain is like a computer with one REALLY big difference. You can back up all the information on your computer and if it crashes you can restore all the information. Well we DO NOT have a restore button. Once the neurons in our brains that held a particular memory or knew how to speak are gone we can’t get them back. There is no restore button. So treat your brain well, you only get one. Image from: http://www.wonderquest.com/images/2004-04-09-brain.jpg

Glycolipids Glycolipids are derivatives of ceramides with carbohydrate directly attached to ceramide In contrast to sphingomyelin they do not have a phosphocholine group .

Glycolipids Are essential components of cell plasma membranes (outer leaflet), but are most abundant in nervous tissues Outside Inside

Glycolipid structure — cerebrosides The carbohydrate component is linked by an O-glycosidic bond to ceramide Cerebrosides contain a single sugar (Glu or Gal) or few sugars; they are abundant in brain and myeline sheath

Glycolipid structure — gangliosides Gangliosides are acidic glycosphingolipids They contain oligosaccharides with terminal, charged N-acetyl neuraminic acids (NANA) Depending on the number of NANA sugars, gangliosides are designated M, D, T, Q (e.g., GM) Ganglioside GM2

Roles of glycolipids Glycolipids have important roles in cell interactions, growth, and development They are very antigenic (e.g., blood group antigens); act as surface receptors for some toxins and viruses; and undergo major changes during cell transformation

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

GLYCOSPHINGOLIPIDS AS DETERMINANTS OF BLOOD GROUPS The human blood groups (O, A, B) are determined in part by the oligosaccharide head groups of these glycosphingolipids. Glc:D-glucose Gal:D-galactose GalNAc:N-acetyl-D-galactosamine Fuc:fucose

Glycolipid degradation Degradation of glycosphingolipids occurs in lysosomes after endocytosis of membrane portions A series of acid hydrolases participate in the degradation Degradation is sequential in the order: last on, first off

Glycolipid degradation Sphingolipidoses result from deficiencies of specific degradative enzymes They are diagnosed by accumulation of specific sphingolipid, enzyme activity measurements, and histologic examination of affected tissue

Biosynthesis of membrane lipids and steroids 1 Gaucher’s - disease Accumulation of glucocerebrosides in reticuloendothelial cells of spleen, liver, and bone marrow the most common of lysosomal storage disease Mental retardation / Glu Gaucher Ceramid b-glukozidáz Biosynthesis of membrane lipids and steroids 1

Biosynthesis of membrane lipids and steroids 1 Krabbe disease Accumulation of Galactosyl ceramide . Gal Ceramid b-galaktosidase Biosynthesis of membrane lipids and steroids 1

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