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MetaCyc Pathway: dermatan sulfate degradation (metazoa)
Inferred from experiment

Pathway diagram: dermatan sulfate degradation (metazoa)

This view shows enzymes only for those organisms listed below, in the list of taxa known to possess the pathway. If an enzyme name is shown in bold, there is experimental evidence for this enzymatic activity.

Superclasses: Degradation/Utilization/AssimilationCarbohydrates DegradationPolysaccharides DegradationGlycans Degradation
Degradation/Utilization/AssimilationCarbohydrates DegradationPolysaccharides DegradationGlycosaminoglycan Degradation
Degradation/Utilization/AssimilationPolymeric Compounds DegradationPolysaccharides DegradationGlycans Degradation
Degradation/Utilization/AssimilationPolymeric Compounds DegradationPolysaccharides DegradationGlycosaminoglycan Degradation

Some taxa known to possess this pathway include : Homo sapiens

Expected Taxonomic Range: Metazoa

Dermatan sulfate is a sulfated glycosaminoglycan composed of repeating disaccharide units of variable composition. Dermatan sulfate is expressed in many mammalian tissues and is the predominant glycan present in the extracellular matrix of skin. Dermatan and dermatan sulfate proteoglycans have also been implicated in cardiovascular disease, tumorigenesis, infection, wound repair, and fibrosis [Trowbridge02]. The most common disaccharide unit in dermatan sulfate is composed of α-L-iduronate and N-acetyl-β-D-galactosamine, which are often sulfated to α-L-iduronate 2-O-sulfate, N-acetyl-β-D-galactosamine 4-sulfate, N-acetyl-D-galactosamine 6-O-sulfate or N-acetyl-D-galactosamine 4,6-bissulfate.Within cells, dermatan sulfate is degraded in two steps.

The initial endohydrolysis is followed by the sequential action of lysosomal exoenzymes to reduce the resulting oligosaccharides to monosaccharides and inorganic sulfate. The first step is catalyzed by a class of human enzymes known as hyaluronidases. This family of enzymes is known to degrade hyaluronan as well as chondroitin sulfate and dermatan sulfate by cleaving internal β-linked (1,4)-glycosidic bonds [Kreil95]. The products of this cleavage vary in size, but fragments of hexa- or tetrasaccharides are often observed.

Following partial catabolism by endoenzymes, dermatan sulfate is degraded from the non-reducing terminus by the sequential action of highly specific lysosomal exoenzymes. These lysosomal exoenzymes include N-acetyl-β-D-galactosaminidases (several forms exist, composed of different combinations of the products of the HEXA and HEXB genes), which remove terminal N-acetyl-β-D-galactosamine residues [Pennybacker96], and α-L-iduronidase, which remove terminal α-L-iduronate residues [Rome78].

A crucial step in the process is the removal of inorganic sulfate from α-L-iduronate 2-O-sulfate residues, which is necessary to enable exit out of the lysosome. The enzyme that catalyzes this step is the iduronate 2-sulfatase ((EC, encoded by IDS). This enzyme removes the C2-sulfate ester bond of non-reducing terminal α-L-iduronate 2-O-sulfate residues only [Bielicki93]. The combined action of these enzyme acts to reduce dermatan sulfate and similar oligosaccharides to monosaccharides, which exit the lysosome and recycled by the cell [Trowbridge02].

Created 16-Aug-2010 by Caspi R, SRI International
Revised 07-Aug-2013 by Weerasinghe D, SRI International


Bielicki93: Bielicki J, Hopwood JJ, Wilson PJ, Anson DS (1993). "Recombinant human iduronate-2-sulphatase: correction of mucopolysaccharidosis-type II fibroblasts and characterization of the purified enzyme." Biochem J 289 ( Pt 1);241-6. PMID: 8424762

Fraser97a: Fraser JR, Laurent TC, Laurent UB (1997). "Hyaluronan: its nature, distribution, functions and turnover." J Intern Med 242(1);27-33. PMID: 9260563

Girish07: Girish KS, Kemparaju K (2007). "The magic glue hyaluronan and its eraser hyaluronidase: a biological overview." Life Sci 80(21);1921-43. PMID: 17408700

Kreil95: Kreil G (1995). "Hyaluronidases--a group of neglected enzymes." Protein Sci 4(9);1666-9. PMID: 8528065

Lindahl78: Lindahl U, Hook M (1978). "Glycosaminoglycans and their binding to biological macromolecules." Annu Rev Biochem 47;385-417. PMID: 354500

Pennybacker96: Pennybacker M, Liessem B, Moczall H, Tifft CJ, Sandhoff K, Proia RL (1996). "Identification of domains in human beta-hexosaminidase that determine substrate specificity." J Biol Chem 271(29);17377-82. PMID: 8663217

Rome78: Rome LH, Garvin AJ, Neufeld EF (1978). "Human kidney alpha-L-iduronidase: purification and characterization." Arch Biochem Biophys 189(2);344-53. PMID: 30407

Trowbridge02: Trowbridge JM, Gallo RL (2002). "Dermatan sulfate: new functions from an old glycosaminoglycan." Glycobiology 12(9);117R-25R. PMID: 12213784

Other References Related to Enzymes, Genes, Subpathways, and Substrates of this Pathway

Latendresse13: Latendresse M. (2013). "Computing Gibbs Free Energy of Compounds and Reactions in MetaCyc."

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Please cite the following article in publications resulting from the use of MetaCyc: Caspi et al, Nucleic Acids Research 42:D459-D471 2014
Page generated by Pathway Tools version 19.5 (software by SRI International) on Wed May 4, 2016, biocyc13.