MetaCyc Pathway: chondroitin sulfate and dermatan sulfate degradation I (bacterial)

Pathway diagram: chondroitin sulfate and dermatan sulfate degradation I (bacterial)

If an enzyme name is shown in bold, there is experimental evidence for this enzymatic activity.

Superclasses: Degradation/Utilization/Assimilation Carbohydrates Degradation Polysaccharides Degradation Glycosaminoglycan Degradation
Degradation/Utilization/Assimilation Polymeric Compounds Degradation Polysaccharides Degradation Glycosaminoglycan Degradation

Some taxa known to possess this pathway include ? : Bacteroides thetaiotaomicron , Pedobacter heparinus , Proteus vulgaris , Streptococcus agalactiae serogroup III

Expected Taxonomic Range: Bacteria

Chondroitin sulfate and dermatan sulfate are major components of connective tissue matrix (such as skin and cartilage) in animals.

They are both glycosaminoglycan polymers composed of repeating disaccharide units, each containing N-acetyl-β-D-galactosamine linked by a (1,3) or (1,4) linkage to a uronic acid, β-D-glucuronate or α-L-iduronate, with extensive N and O-sulfation. Sulfation occurs to various degrees at position 2 of uronic acid and at positions 4 or 6, or both, of galactosamine. In addition, the amino group of galactosamine is acetylated

Many microorganisms have enzymes that enable them to degrade glycosaminoglycans [Sutherland95]. This ability is particularly important for soil bacteria, which may depend on connective tissues in animal carcasses as a nutrient source.

There are several steps in the degradation process. It starts with the cleavage of the polymer into smaller fragments, initially tetra- and hexasaccharides, but ultimately disaccharides. The process continues with the removal of the sulfate groups, and ends with the final degradation of the disaccharides into individual sugars, a step that has not been characterized yet.

The lyases that break the polymer to smaller fragments are classified based on the position of cleavage as either endo-lyases or exo-lyases. The endolytic enzyme can produce products of several sizes, although the final product tends to be disaccharides. The exo-lyases cleave dissaccharide molecules from the non-reducing end of the polymer chain [Hamai97]. Some lyases, known as chondroitinase AC, can act only on chondroitin sulfate A and chondroitin sulfate C (that contain β-D-glucuronate), some, known as chondroitinase B, can act only on dermatan sulfate (that contains α-L-iduronate), and some, known as condroitinase ABC, can act on both [Tkalec00, Hamai97].

The lyases act by the removal of a relatively acidic C5 proton of the uronic acid (C5 is the carbon linked to the carboxylic group) followed by the elimination of the hexosamine linked to C4, resulting in the formation of an unsaturated C4-C5 bond on the hexuronic acid moiety of the resulting disacchrides.

Chondroitin ABC lyases may help in the regeneration of spinal cord injuries that were thought for a long time to be incurable. Injection of chondroitinase ABC at sites of central nervous system injury, where a glial scar develops, removes the GAG components of ECM chondroitin sulfate proteoglycans and attenuates the inhibitory effects to axon growth [Bradbury02, Bradbury02, Olson02].

The removal of the sulfate groups is catalyzed by specialized sulfatases that can remove the sulfate groups at either the 4 or 6 positions. The sulfatases have been purified from Proteus vulgaris but the genes that encode them have not been identified [Yamagata68].

Created 10-Aug-2010 by Caspi R , SRI International


Bradbury02: Bradbury EJ, Moon LD, Popat RJ, King VR, Bennett GS, Patel PN, Fawcett JW, McMahon SB (2002). "Chondroitinase ABC promotes functional recovery after spinal cord injury." Nature 416(6881);636-40. PMID: 11948352

Hamai97: Hamai A, Hashimoto N, Mochizuki H, Kato F, Makiguchi Y, Horie K, Suzuki S (1997). "Two distinct chondroitin sulfate ABC lyases. An endoeliminase yielding tetrasaccharides and an exoeliminase preferentially acting on oligosaccharides." J Biol Chem 272(14);9123-30. PMID: 9083041

Olson02: Olson L (2002). "Medicine: clearing a path for nerve growth." Nature 416(6881);589-90. PMID: 11948332

Sutherland95: Sutherland IW (1995). "Polysaccharide lyases." FEMS Microbiol Rev 16(4);323-47. PMID: 7654407

Tkalec00: Tkalec AL, Fink D, Blain F, Zhang-Sun G, Laliberte M, Bennett DC, Gu K, Zimmermann JJ, Su H (2000). "Isolation and expression in Escherichia coli of cslA and cslB, genes coding for the chondroitin sulfate-degrading enzymes chondroitinase AC and chondroitinase B, respectively, from Flavobacterium heparinum." Appl Environ Microbiol 66(1);29-35. PMID: 10618199

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

Yamagata68: Yamagata T, Saito H, Habuchi O, Suzuki S (1968). "Purification and properties of bacterial chondroitinases and chondrosulfatases." J Biol Chem 243(7);1523-35. PMID: 5647268

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

Fethiere99: Fethiere J, Eggimann B, Cygler M (1999). "Crystal structure of chondroitin AC lyase, a representative of a family of glycosaminoglycan degrading enzymes." J Mol Biol 288(4);635-47. PMID: 10329169

Hashimoto99: Hashimoto W, Kobayashi E, Nankai H, Sato N, Miya T, Kawai S, Murata K (1999). "Unsaturated glucuronyl hydrolase of Bacillus sp. GL1: novel enzyme prerequisite for metabolism of unsaturated oligosaccharides produced by polysaccharide lyases." Arch Biochem Biophys 368(2);367-74. PMID: 10441389

Huang01a: Huang W, Boju L, Tkalec L, Su H, Yang HO, Gunay NS, Linhardt RJ, Kim YS, Matte A, Cygler M (2001). "Active site of chondroitin AC lyase revealed by the structure of enzyme-oligosaccharide complexes and mutagenesis." Biochemistry 40(8);2359-72. PMID: 11327856

Huang03: Huang W, Lunin VV, Li Y, Suzuki S, Sugiura N, Miyazono H, Cygler M (2003). "Crystal structure of Proteus vulgaris chondroitin sulfate ABC lyase I at 1.9A resolution." J Mol Biol 328(3);623-34. PMID: 12706721

Huang99c: Huang W, Matte A, Li Y, Kim YS, Linhardt RJ, Su H, Cygler M (1999). "Crystal structure of chondroitinase B from Flavobacterium heparinum and its complex with a disaccharide product at 1.7 A resolution." J Mol Biol 294(5);1257-69. PMID: 10600383

Huckerby05: Huckerby TN, Nieduszynski IA, Giannopoulos M, Weeks SD, Sadler IH, Lauder RM (2005). "Characterization of oligosaccharides from the chondroitin/dermatan sulfates. 1H-NMR and 13C-NMR studies of reduced trisaccharides and hexasaccharides." FEBS J 272(24);6276-86. PMID: 16336265

Itoh04a: Itoh T, Akao S, Hashimoto W, Mikami B, Murata K (2004). "Crystal structure of unsaturated glucuronyl hydrolase, responsible for the degradation of glycosaminoglycan, from Bacillus sp. GL1 at 1.8 A resolution." J Biol Chem 279(30);31804-12. PMID: 15148314

Itoh06: Itoh T, Hashimoto W, Mikami B, Murata K (2006). "Substrate recognition by unsaturated glucuronyl hydrolase from Bacillus sp. GL1." Biochem Biophys Res Commun 344(1);253-62. PMID: 16630576

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

Linhardt95: Linhardt RJ, Laliberte M, Gu K, Zimmermann J (1995). "Purification, characterization and specificity of chondroitin lyases and glycuronidase from Flavobacterium heparinum." Biochem J 312 ( Pt 2);569-77. PMID: 8526872

Maruyama09: Maruyama Y, Nakamichi Y, Itoh T, Mikami B, Hashimoto W, Murata K (2009). "Substrate specificity of streptococcal unsaturated glucuronyl hydrolases for sulfated glycosaminoglycan." J Biol Chem 284(27);18059-69. PMID: 19416976

Pojasek01: Pojasek K, Shriver Z, Kiley P, Venkataraman G, Sasisekharan R (2001). "Recombinant expression, purification, and kinetic characterization of chondroitinase AC and chondroitinase B from Flavobacterium heparinum." Biochem Biophys Res Commun 286(2);343-51. PMID: 11500043

Pojasek02: Pojasek K, Raman R, Kiley P, Venkataraman G, Sasisekharan R (2002). "Biochemical characterization of the chondroitinase B active site." J Biol Chem 277(34);31179-86. PMID: 12063249

Saito68: Saito H, Yamagata T, Suzuki S (1968). "Enzymatic methods for the determination of small quantities of isomeric chondroitin sulfates." J Biol Chem 243(7);1536-42. PMID: 4231029

Sato94a: Sato N, Shimada M, Nakajima H, Oda H, Kimura S (1994). "Cloning and expression in Escherichia coli of the gene encoding the Proteus vulgaris chondroitin ABC lyase." Appl Microbiol Biotechnol 41(1);39-46. PMID: 7512814

Shaya08: Shaya D, Hahn BS, Bjerkan TM, Kim WS, Park NY, Sim JS, Kim YS, Cygler M (2008). "Composite active site of chondroitin lyase ABC accepting both epimers of uronic acid." Glycobiology 18(3);270-7. PMID: 18227125

Suzuki68a: Suzuki S, Saito H, Yamagata T, Anno K, Seno N, Kawai Y, Furuhashi T (1968). "Formation of three types of disulfated disaccharides from chondroitin sulfates by chondroitinase digestion." J Biol Chem 243(7);1543-50. PMID: 5647269

Zhang09c: Zhang Z, Park Y, Kemp MM, Zhao W, Im AR, Shaya D, Cygler M, Kim YS, Linhardt RJ (2009). "Liquid chromatography-mass spectrometry to study chondroitin lyase action pattern." Anal Biochem 385(1);57-64. PMID: 18992215

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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 SRI International Pathway Tools version 19.0 on Fri Mar 27, 2015, biocyc14.