BCHS-4361-09-GAUCHER_39324

BCHS-4361-09-GAUCHER - GAUCHER DISEASE A SPHINGOLIPIDOSIS Sphingolipidoses are inherited lysosomal storage diseases that are caused by impaired

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GAUCHER DISEASE: A SPHINGOLIPIDOSIS Sphingolipidoses are inherited lysosomal storage diseases that are caused by impaired function of various lysosomal enzymes and which result in massive accumulation of an intermediate in sphingolipid metabolism. The enzyme deficiency usually affects a step in the catabolism of the sphingolipid. Sphingolipids contain a long chain-nitrogen-containing base: sphingosine CH 3 (CH 2 ) 12 CH=CH-CHOH-CHNH 2 -CH 2 OH Sphingosine is the trivial name of a member of the family of sphinganines and is the most common.
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Four major phospholipids in mammalian cell membranes
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I. SPHINGOLIPID STRUCTURE AND METABOLISM Other sphinganines include dihydrosphingosine and the saturated and unsaturated C 20 homologs. Ceramides consist of a sphingosine to which is attached an acyl chain through the amino group. Also known as N- acylsphingosines. CH 3 (CH 2 ) 12 -CH=CH-CHOH-CH-CH 2 OH NH C=O R where R is often, but not always a VLCFA. These VLCFA are usually saturated and may be hydroxylated on the α - carbon.
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Structure of a ceramide (N-acylsphingosine) Structure of sphingomyelin Sphingosine
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II. SPHINGOLIPID STRUCTURE AND METABOLISM The synthesis of sphingosine starts with palmitoyl CoA and serine (see next slides). Ceramide is then formed from sphingosine by addition of the acyl chain. It is usually present in cells at low levels, but when its concentration rises, a pathway is activated that results in programmed cell death (apoptosis). Naturally occurring sphingolipids have groups linked to the -CH 2 OH moiety (at C-1 of ceramide). Sphingomyelin, the most abundant sphingolipid, has a phosphocholine group attached at C-1. Glycosphingolipids are compounds in which one or more carbohydrate groups are attached at C-1. They include glycosylceramides (sometimes called cerebrosides ) and gangliosides.
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Sphingolipid Structures Sphingolipids (phospho- or glycolipids) CH HC H 2 C N H O C(CH 2 ) 22 CH 3 X O HO CH=CH(CH 2 ) 12 CH 3 CH HC H 2 C N H O C(CH 2 ) 22 CH 3 H O HO CH=CH(CH 2 ) 12 CH 3 CH HC H 2 C N H O C(CH 2 ) 22 CH 3 Glc O HO CH=CH(CH 2 ) 12 CH 3 CH HC H 2 C N H O C(CH 2 ) 22 CH 3 Glc-Gal O HO CH=CH(CH 2 ) 12 CH 3 CH HC H 2 C N H O C(CH 2 ) 22 CH 3 O HO CH=CH(CH 2 ) 12 CH 3 Glc Gal Neu5Ac GalNAc S General Structure Ceramide Sphingomyelin PC Glucocerebroside LactosylCeramide Ganglioside CH HC H 2 C N H O C(CH 2 ) 22 CH 3 PO 3 CH 2 CH 2 N(CH 3 ) 2 O HO CH=CH(CH 2 ) 12 CH 3
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R is often a very long chain fatty acid (>20 carbons)
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III. SPHINGOLIPID STRUCTURE AND METABOLISM Sphingomyelin is the only common sphingo- phospholipid. The synthesis of sphingomyelin occurs as folllows: Ceramide + phosphatidylcholine sphingomyelin + 1,2-diacylglycerol In membrane bilayers, the hydrophobic chain of sphingosine may be thought of as equivalent to a fatty acyl chain. Both are highly hydrophobic.
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IV. SPHINGOLIPID STRUCTURE AND METABOLISM Cerebrosides contain either a glucose or a galactose group that form a glycosidic bond at
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This note was uploaded on 01/23/2011 for the course BCHS 4361 taught by Professor Echberg during the Spring '09 term at University of Houston.

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BCHS-4361-09-GAUCHER - GAUCHER DISEASE A SPHINGOLIPIDOSIS Sphingolipidoses are inherited lysosomal storage diseases that are caused by impaired

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