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/Assimilation → Carbohydrates Degradation → Polysaccharides Degradation → Glycans Degradation|
|Degradation/Utilization/Assimilation → Carbohydrates Degradation → Polysaccharides Degradation → Glycosaminoglycan Degradation|
|Degradation/Utilization/Assimilation → Polymeric Compounds Degradation → Polysaccharides Degradation → Glycans Degradation|
|Degradation/Utilization/Assimilation → Polymeric Compounds Degradation → Polysaccharides Degradation → Glycosaminoglycan 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-β-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 complex ((EC 126.96.36.199, 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].
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
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
©2014 SRI International, 333 Ravenswood Avenue, Menlo Park, CA 94025-3493