Download
extracellular matrix and glycolipid disorders n.
Skip this Video
Loading SlideShow in 5 Seconds..
Extracellular Matrix and Glycolipid Disorders PowerPoint Presentation
Download Presentation
Extracellular Matrix and Glycolipid Disorders

Extracellular Matrix and Glycolipid Disorders

258 Vues Download Presentation
Télécharger la présentation

Extracellular Matrix and Glycolipid Disorders

- - - - - - - - - - - - - - - - - - - - - - - - - - - E N D - - - - - - - - - - - - - - - - - - - - - - - - - - -
Presentation Transcript

  1. Extracellular Matrix and Glycolipid Disorders Eric Niederhoffer SIU-SOM Proteins conjugated to saccharides lacking a serial repeat unit GP Protein >> carbohydrate Proteins conjugated to polysaccharides with serial repeat units Lysosomal Hydrolases PG Carbohydrate >> protein Repeat unit HexN and HexUA GAGs (MPs) SL (Cb or Gan) Cer (S + FA) with MS or OS

  2. a-Mannosidase b-N-Acetylhexosaminidases A&B 4-L-Aspartylglycosylamine amidohydrolase b-Mannosidase b-Galactosidase a-Fucosidase Sialidase Oligosaccharidoses a-Mannosidosis GM2 gangliosidosis variant O (Sandhoff-Jatzkewitz disease) Aspartylglycosylaminuria 5 6 4 NANA Gal GlcNAc a b Man b 6 5 3 NANA Gal GlcNAc 4 b a a 7 2 1 Man GlcNAc GlcNAc Asn 5 6 a NANA Gal GlcNAc 4 3 b b 8 b a Man b GlcNAc Fuc 5 6 NANA Gal GlcNAc 4 a b Typical Asn-GlcNAc OS structure b-Mannosidosis GM1 gangliosidosis Fucosidosis Mucolipidosis I (Sialidosis) What’s 1?

  3. b-glucuronidase iduronate sulfatase heparan N-sulfatase a-L-iduronidase Acetyl-CoA: a-glucosaminide acetyltransferase N-acetylgalactosamine sulfatase N-acetylglucosaminidase b-hexosaminidase A,B,S N-acetylgalactose-6-sulfatase N-acetylglucosamine-6-sulfatase b-galactosidase Glycosaminoglycoses(mucopolysaccharidoses) Mucolipodosis VII Sanfilippo’s A Hunter’s Hurler-Scheie Aldurazyme® (laronidase) Sanfilippo’s C Maroteaux-Lamy 2 4 5 GalNAc GlcUA GalNAc DS IdUA a b b b 1 3 OSO3H OSO3H OSO3H 2 7,9 5 9 GlcNAc HS GlcN GlcUA IdUA a a a b 1 6 8 OSO3H OSO3H OSO3H Sandhoff/Tay-Sachs Sanfilippo’s B 11 4 Gal KS Gal GlcNAc GlcNAc b b b b 10 8 OSO3H OSO3H OSO3H Morquio’s A Sanfilippo’s D Morquio’s B

  4. neuraminidase (sialidase) NANA NANA b-galactosidase b b b b Gal GalNAc Gal Cer Glu NANA b b b b Cer Glu Gal GalNAc Gal NANA b-hexosaminidase A GM2 activator b b b Cer Glu Gal GalNAc NANA neuraminidase (sialidase) SAP-B b b Cer Glu Gal a-galactosidase A SAP-B b b b b a Cer Glu Gal Cer Glu Gal Gal b-galactosidase SAP-B, SAP-C b Cer Glu b-hexosaminidase A&B b b b a Cer Glu Gal Gal GalNAc b-glucosylceramidase SAP-C b-galactosylceramidase SAP-A, SAP-C b Cer PC Cer Cer Gal arylsulfatase A SAP-B sphingomyelinase b Cer Gal SO3H S + FA Gangliosidoses Generalized gangliosidosis GD1 GM1 Tay-Sachs disease GM2 Sialidosis GM3 Fabry’s disease Sandhoff’s disease Gaucher’s disease Krabbe’s disease Cerezyme Metachromatic leukodystrophy Niemann-Pick disease

  5. Targeting of Lysosomal Enzymes to Lysosomes Addition of M6P to lysosomal enzymes Recognition by MPRs M6P independent pathways