Dermatan sulfate is a glycosaminoglycan (formerly called a mucopolysaccharide) found mostly in skin, but also in blood vessels, heart valves, tendons, and lungs.

It is also referred to as chondroitin sulfate B, although it is no longer classified as a form of chondroitin sulfate by most sources. The formula is C₁₄H₂₁NO₁₅S. This carbohydrate is composed of linear polymers of disaccharide units that contain, N-acetyl galactosamine (GalNAc) and iduronic acid (IdoA). These repeating units are sulfated at a variety of positions. Dermatan sulfate is a component of the compound sulodexide.

• Trowbridge JM, Gallo RL (September 2002). “Dermatan sulfate: new functions from an old glycosaminoglycan”. Glycobiology. 12 (9): 117R–125R. doi:10.1093/glycob/cwf066. PMID 12213784.
• “Dermatan sulfate”.
• Lasierra-Cirujeda J, Coronel P, Aza M, Gimeno M (2010). “Use of sulodexide in patients with peripheral vascular disease”. Journal of Blood Medicine. 1: 105–115. doi:10.2147/JBM.S10558. PMC 3262318. PMID 22282689. Sulodexide is a highly purified glycosaminoglycan (GAG) obtained from porcine digestive mucosa and is composed of a mixture of 80% heparan sulfate (an electrophoretically fast moving fraction with a low molecular weight of 7000 Da and affinity for antithrombin III) and 20% dermatan sulfate with a high molecular weight (25,000 Da) and affinity for the heparin II cofactor.

Function

Dermatan sulfate may have roles in coagulation, cardiovascular disease, carcinogenesis, infection, wound repair, maintaining the shape of galactosamine 4-sulfate, skin, and fibrosis.

• Trowbridge JM, Gallo RL (September 2002). “Dermatan sulfate: new functions from an old glycosaminoglycan”. Glycobiology. 12 (9): 117R–125R. doi:10.1093/glycob/cwf066. PMID 12213784.

Pathology

Dermatan sulfate accumulates abnormally in several of the mucopolysaccharidosis disorders.

An excess of dermatan sulfate in the mitral valve is characteristic of myxomatous degeneration of the leaflets leading to redundancy of valve tissue and ultimately, mitral valve prolapse (into the left atrium) and insufficiency. This chronic prolapse occurs mainly in women over the age of 60, and can predispose the patient to mitral annular calcification. Mitral valve insufficiency can lead to eccentric (volume dependent or dilated) hypertrophy and eventually left heart failure if untreated.

See also

• Iduronic acid
  • l-Iduronic acid (IUPAC abbr.: IdoA) is the major uronic acid component of the glycosaminoglycans (GAGs) dermatan sulfate, and heparin. It is also present in heparan sulfate, although here in a minor amount relative to its carbon-5 epimer glucuronic acid.
  • IdoA is a hexapyranose sugar. Most hexapyranoses are stable in one of two chair conformations ¹C₄ or ⁴C₁. l-iduronate is different and adopts more than one solution conformation, with an equilibrium existing between three low-energy conformers. These are the ¹C₄ and ⁴C₁ chair forms and an additional ²S₀ skew-boat conformation.
  • IdoA may be modified by the addition of an O-sulfate group at carbon position 2 to form 2-O-sulfo-l-iduronic acid (IdoA2S).
  • In 2000, LK Hallak described the importance of this sugar in respiratory syncytial virus (RSV) infection. Dermatan sulfate and heparan sulfate were the only GAGs containing IdoA, and they were the only ones that inhibited RSV infection in cell culture.
    • Hallak LK, Collins PL, Knudson W, Peeples ME (2000). “Iduronic acid-containing glycosaminoglycans on target cells are required for efficient respiratory syncytial virus infection”. Virology. 271 (2): 264–75. doi:10.1006/viro.2000.0293. PMID 10860881.
  • When internally positioned within an oligosaccharide, the ¹C₄ and ²S₀ conformations (shown below for IdoA2S) predominate.
  • Proton NMR spectroscopy can be used to track changes in the balance of this equilibrium.
    • Ferro, D. R. Provasoli, A. (1990). “Conformer populations of L-iduronic acid residues in glycosaminoglycan sequences”. Carbohydr. Res. 195 (2): 157–167. doi:10.1016/0008-6215(90)84164-P. PMID 2331699.
• N-Acetylgalactosamine
  • N-Acetylgalactosamin (GalNAc), is an amino sugar derivative of galactose.
    • Function – In humans it is the terminal carbohydrate forming the antigen of blood group A. It is typically the first monosaccharide that connects serine or threonine in particular forms of protein O-glycosylation. N-Acetylgalactosamine is necessary for intercellular communication, and is concentrated in sensory nerve structures of both humans and animals. GalNAc is also used as a targeting ligand in investigational antisense oligonucleotides and siRNA therapies targeted to the liver, where it binds to the asialoglycoprotein receptors on hepatocytes. 
      • Donald M. Marcus; Elvin A. Kabat; Gerald Schiffman (1964). “Immunochemical Studies on Blood Groups. XXXI. Destruction of Blood Group A Activity by an Enzyme from Clostridium tertium Which Deacetylates N-Acetylgalactosamine in Intact Blood Group Substances”. Biochemistry. 3 (3): 437–443. doi:10.1021/bi00891a023.
      • Nair, Jayaprakash K; Willoughby, Jennifer L. S; Chan, Amy; Charisse, Klaus; Alam, Md. Rowshon; Wang, Qianfan; Hoekstra, Menno; Kandasamy, Pachamuthu; Kel’In, Alexander V; Milstein, Stuart; Taneja, Nate; o’Shea, Jonathan; Shaikh, Sarfraz; Zhang, Ligang; Van Der Sluis, Ronald J; Jung, Michael E; Akinc, Akin; Hutabarat, Renta; Kuchimanchi, Satya; Fitzgerald, Kevin; Zimmermann, Tracy; Van Berkel, Theo J. C; Maier, Martin A; Rajeev, Kallanthottathil G; Manoharan, Muthiah (2014). “Multivalent N-Acetylgalactosamine-Conjugated siRNA Localizes in Hepatocytes and Elicits Robust RNAi-Mediated Gene Silencing”. Journal of the American Chemical Society. 136 (49): 16958–16961. doi:10.1021/ja505986a. PMID 25434769
    • See also
      • Galactosamine
      • Globoside
      • N-Acetylglucosamine (local links)
        • N-Acetylglucosamine (GlcNAc) is an amide derivative of the monosaccharide glucose. It is a secondary amide between glucosamine and acetic acid. It is significant in several biological systems. It is part of a biopolymer in the bacterial cell wall, which is built from alternating units of GlcNAc and N-acetylmuramic acid (MurNAc), cross-linked with oligopeptides at the lactic acid residue of MurNAc. This layered structure is called peptidoglycan (formerly called murein). GlcNAc is the monomeric unit of the polymer chitin, which forms the exoskeletons of arthropods like insects and crustaceans. It is the main component of the radulas of mollusks, the beaks of cephalopods, and a major component of the cell walls of most fungi. Polymerized with glucuronic acid, it forms hyaluronan. GlcNAc has been reported to be an inhibitor of elastase release from human polymorphonuclear leukocytes (range 8–17% inhibition), however this is much weaker than the inhibition seen with N-acetylgalactosamine (range 92–100%).
          • Kamel M, Hanafi M, Bassiouni M (1991). “Inhibition of elastase enzyme release from human polymorphonuclear leukocytes by N-acetyl-galactosamine and N-acetyl-glucosamine”. Clinical and Experimental Rheumatology. 9 (1): 17–21. PMID 2054963.
        • Medical uses – It has been proposed as a treatment for autoimmune diseases and recent tests have claimed some success.
          • Grigorian A, Araujo L, Naidu NN, Place DJ, Choudhury B, Demetriou M (November 2011). “N-acetylglucosamine inhibits T-helper 1 (Th1)/T-helper 17 (Th17) cell responses and treats experimental autoimmune encephalomyelitis”. The Journal of Biological Chemistry. 286 (46): 40133–40141. doi:10.1074/jbc.M111.277814. PMC 3220534. PMID 21965673.
          • Sy M, Newton BL, Pawling J, Hayama KL, Cordon A, Yu Z, et al. (September 2023). “N-acetylglucosamine inhibits inflammation and neurodegeneration markers in multiple sclerosis: a mechanistic trial”. Journal of Neuroinflammation. 20 (1): 209. doi:10.1186/s12974-023-02893-9. PMC 10498575. PMID 37705084.
        • O-GlcNAc – O-GlcNAcylation is the process of adding a single N-acetylglucosamine sugar to the serine or threonine of a protein. Comparable to phosphorylation, addition or removal of N-acetylglucosamine is a means of activating or deactivating enzymes or transcription factors. In fact, O-GlcNAcylation and phosphorylation often compete for the same serine/threonine sites. O-GlcNAcylation most often occurs on chromatin proteins, and is often seen as a response to stress.
          • Hart GW, Slawson C, Ramirez-Correa G, Lagerlof O (2011). “Cross talk between O-GlcNAcylation and phosphorylation: roles in signaling, transcription, and chronic disease”. Annual Review of Biochemistry. 80: 825–858. doi:10.1146/annurev-biochem-060608-102511. PMC 3294376. PMID 21391816.
        • Hyperglycemia increases O-GlcNAcylation, leading to insulin resistance. Increased O-GlcNAcylation due to hyperglycemia is evidently a dysfunctional form of O-GlcNAcylation. O-GlcNAcylation decline in the brain with age is associated with cognitive decline. When O-GlcNAcylation was increased in the hippocampus of aged mice, spatial learning and memory improved.
          • Ma J, Hart GW (August 2013). “Protein O-GlcNAcylation in diabetes and diabetic complications”. Expert Review of Proteomics. 10 (4): 365–380. doi:10.1586/14789450.2013.820536. PMC 3985334. PMID 23992419.
          • Wheatley EG, Albarran E, White CW, Bieri G, Sanchez-Diaz C, Pratt K, et al. (October 2019). “Neuronal O-GlcNAcylation Improves Cognitive Function in the Aged Mouse Brain”. Current Biology. 29 (20): 3359–3369.e4. doi:10.1016/j.cub.2019.08.003. PMC 7199460. PMID 31588002.
        • See also
          • Keratan sulfate (local links)
          • N-Acetylgalactosamine (GalNAc)
          • N-Acetyllactosamine synthase
          • Wheat germ agglutinin, a plant lectin that binds to this substrate
        •  

References

1. Trowbridge JM, Gallo RL (September 2002). “Dermatan sulfate: new functions from an old glycosaminoglycan“. Glycobiology. 12 (9): 117R–125R. doi:10.1093/glycob/cwf066. PMID 12213784.
2. “Dermatan sulfate”.
3. Lasierra-Cirujeda J, Coronel P, Aza M, Gimeno M (2010). “Use of sulodexide in patients with peripheral vascular disease”. Journal of Blood Medicine. 1: 105–115. doi:10.2147/JBM.S10558. PMC 3262318. PMID 22282689. Sulodexide is a highly purified glycosaminoglycan (GAG) obtained from porcine digestive mucosa and is composed of a mixture of 80% heparan sulfate (an electrophoretically fast moving fraction with a low molecular weight of 7000 Da and affinity for antithrombin III) and 20% dermatan sulfate with a high molecular weight (25,000 Da) and affinity for the heparin II cofactor.
4.  Donald M. Marcus; Elvin A. Kabat; Gerald Schiffman (1964). “Immunochemical Studies on Blood Groups. XXXI. Destruction of Blood Group A Activity by an Enzyme from Clostridium tertium Which Deacetylates N-Acetylgalactosamine in Intact Blood Group Substances”. Biochemistry. 3 (3): 437–443. doi:10.1021/bi00891a023.
5. Nair, Jayaprakash K; Willoughby, Jennifer L. S; Chan, Amy; Charisse, Klaus; Alam, Md. Rowshon; Wang, Qianfan; Hoekstra, Menno; Kandasamy, Pachamuthu; Kel’In, Alexander V; Milstein, Stuart; Taneja, Nate; o’Shea, Jonathan; Shaikh, Sarfraz; Zhang, Ligang; Van Der Sluis, Ronald J; Jung, Michael E; Akinc, Akin; Hutabarat, Renta; Kuchimanchi, Satya; Fitzgerald, Kevin; Zimmermann, Tracy; Van Berkel, Theo J. C; Maier, Martin A; Rajeev, Kallanthottathil G; Manoharan, Muthiah (2014). “Multivalent N-Acetylgalactosamine-Conjugated siRNA Localizes in Hepatocytes and Elicits Robust RNAi-Mediated Gene Silencing”. Journal of the American Chemical Society. 136 (49): 16958–16961. doi:10.1021/ja505986a. PMID 25434769.
6. Hallak LK, Collins PL, Knudson W, Peeples ME (2000). “Iduronic acid-containing glycosaminoglycans on target cells are required for efficient respiratory syncytial virus infection”. Virology. 271 (2): 264–75. doi:10.1006/viro.2000.0293. PMID
7. Ferro, D. R. Provasoli, A. (1990). “Conformer populations of L-iduronic acid residues in glycosaminoglycan sequences”. Carbohydr. Res. 195 (2): 157–167. doi:10.1016/0008-6215(90)84164-P. PMID 2331699.
8.  Kamel M, Hanafi M, Bassiouni M (1991). “Inhibition of elastase enzyme release from human polymorphonuclear leukocytes by N-acetyl-galactosamine and N-acetyl-glucosamine”. Clinical and Experimental Rheumatology. 9 (1): 17–21. PMID 2054963.
9. Grigorian A, Araujo L, Naidu NN, Place DJ, Choudhury B, Demetriou M (November 2011). “N-acetylglucosamine inhibits T-helper 1 (Th1)/T-helper 17 (Th17) cell responses and treats experimental autoimmune encephalomyelitis”. The Journal of Biological Chemistry. 286 (46): 40133–40141. doi:10.1074/jbc.M111.277814. PMC 3220534. PMID 21965673.
10. Sy M, Newton BL, Pawling J, Hayama KL, Cordon A, Yu Z, et al. (September 2023). “N-acetylglucosamine inhibits inflammation and neurodegeneration markers in multiple sclerosis: a mechanistic trial”. Journal of Neuroinflammation. 20 (1): 209. doi:10.1186/s12974-023-02893-9. PMC 10498575. PMID 37705084.
11. Hart GW, Slawson C, Ramirez-Correa G, Lagerlof O (2011). “Cross talk between O-GlcNAcylation and phosphorylation: roles in signaling, transcription, and chronic disease”. Annual Review of Biochemistry. 80: 825–858. doi:10.1146/annurev-biochem-060608-102511. PMC 3294376. PMID 21391816.
12. Ma J, Hart GW (August 2013). “Protein O-GlcNAcylation in diabetes and diabetic complications”. Expert Review of Proteomics. 10 (4): 365–380. doi:10.1586/14789450.2013.820536. PMC 3985334. PMID 23992419.
13. Wheatley EG, Albarran E, White CW, Bieri G, Sanchez-Diaz C, Pratt K, et al. (October 2019). “Neuronal O-GlcNAcylation Improves Cognitive Function in the Aged Mouse Brain”. Current Biology. 29 (20): 3359–3369.e4. doi:10.1016/j.cub.2019.08.003. PMC 7199460. PMID 31588002.

External links

• Dermatan+sulfate at the U.S. National Library of Medicine Medical Subject Headings (MeSH)
• Media related to N-Acetylgalactosamine at Wikimedia Commons
• Re Multiple Sclerosis

Antithrombotics (thrombolytics, anticoagulants and antiplatelet drugs) (B01)

Polysaccharides: glycosaminoglycans

Categories: 

• Glycosaminoglycans
• Sulfate esters
• Hexosamines
• Acetamides
• Membrane biology