{{short description|Class of chemical compounds}} {{Distinguish|Keratin}} thumb|right|Chemical structure of keratan sulfate '''Keratan sulfate''' ('''KS'''), also called '''keratosulfate''', is any of several sulfated glycosaminoglycans (structural carbohydrates) that have been found especially in the cornea, cartilage, and bone. It is also synthesized in the central nervous system where it participates both in development<ref name="pmid9087531">{{cite journal |vauthors=Miller B, Sheppard AM, Pearlman AL |title=Developmental expression of keratan sulfate-like immunoreactivity distinguishes thalamic nuclei and cortical domains |journal=J. Comp. Neurol. |volume=380 |issue=4 |pages=533–52 |date=April 1997 |pmid=9087531|doi=10.1002/(SICI)1096-9861(19970421)380:4<533::AID-CNE9>3.0.CO;2-2}}</ref> and in the glial scar formation following an injury.<ref name="pmid17185507">{{cite journal |vauthors=Zhang H, Uchimura K, Kadomatsu K |title=Brain keratan sulfate and glial scar formation |journal=Ann. N. Y. Acad. Sci. |volume=1086 |issue= 1|pages=81–90 |date=November 2006 |pmid=17185507 |doi=10.1196/annals.1377.014 |bibcode = 2006NYASA1086...81Z }}</ref> Keratan sulfates are large, highly hydrated molecules which in joints can act as a cushion to absorb mechanical shock.
==Structure== Like other glycosaminoglycans keratan sulfate is a linear polymer that consists of a repeating disaccharide unit. Keratan sulfate occurs as a proteoglycan (PG) in which KS chains are attached to cell-surface or extracellular matrix proteins, termed core proteins. KS core proteins include lumican, keratocan, mimecan, fibromodulin, PRELP, osteoadherin, and aggrecan.
The basic repeating disaccharide unit within keratan sulfate is -3Galβ1-4GlcNAc6Sβ1-. This can be sulfated at carbon position 6 (C6) of either or both the Gal or GlcNAc monosaccharides. However, the detailed primary structure of specific KS types are best considered to be composed of three regions:<ref name=tai>{{cite journal |vauthors=Tai GH, Huckerby TN, Nieduszynski IA | title = Multiple non-reducing chain termini isolated from bovine corneal keratan sulfates | journal = J. Biol. Chem. | year=1996 | volume=271 | issue =38 | pages=23535–23546 | pmid = 8798563 | doi = 10.1074/jbc.271.38.23535| doi-access =free }}</ref>
*A linkage region, at one end of which the KS chain is linked to the core protein. *A repeat region, composed of the -3Galβ1-4GlcNAcβ1- repeating disaccharide unit and *A chain capping region, occurring at the opposite end of the KS chain to the protein linkage region.
The monosaccharide mannose is found within the linkage region of keratan sulfate type I (KSI). Disaccharides within the repeating region of KSII may be fucosylated and N-Acetylneuraminic acid caps the end of all keratan sulfate type II (KSII) chains and up to 70% of KSI type chains.<ref name=funderburgh>{{cite journal | author = Funderburgh JL. | title = Keratan sulfate: structure, biosynthesis, and function | journal = Glycobiology | year=2000 | volume=10 | issue =10 | pages=951–958 | pmid = 11030741 | doi = 10.1093/glycob/10.10.951| doi-access = free }}</ref>
===KS classes=== The designations KSI and KSII were originally assigned on the basis of the tissue type from which the keratan sulfate was isolated. KSI was isolated from corneal tissue and KSII from skeletal tissue.<ref>{{cite journal | vauthors = Meyer K, Linker A, etal | title = The mucopolysaccharides of bovine cornea | journal = J. Biol. Chem. | date = 1 December 1953 | volume = 205 | issue = 2 | pages = 611–616 | doi = 10.1016/S0021-9258(18)49203-4 | doi-access = free | pmid = 13129238 }}</ref><ref>{{cite journal |author1=Meyer K |author2=Hoffman P. |author3=Linker A. | title = Mucopolysaccharides of Costal Cartilage | journal = Science | year=1958 | volume=128 | issue=3329 | pages=896 | pmid = 13592269 | doi = 10.1126/science.128.3329.896|bibcode = 1958Sci...128..896M }}</ref> Minor monosaccharide compositional differences exist between KS extracted from both sources and even KS extracted from the same source. However, major differences occur in the way each KS type is joined to its core protein.<ref>{{cite journal | vauthors = Seno N, Meyer K, etal | title = Variations in Keratosulfates | journal = J. Biol. Chem. | date = 1 March 1965 | volume = 240 | pages = 1005–1019 | pmid = 14284693 | issue = 3 | doi = 10.1016/S0021-9258(18)97528-9 | doi-access = free }}</ref> The designations KSI and KSII are now based upon these protein linkage differences. KSI is ''N''-linked to specific asparagine amino acids via ''N''-acetylglucosamine and KSII is ''O''-linked to specific serine or threonine amino acids via ''N''-acetylgalactosamine.<ref name=Nieduszynski>{{cite journal |vauthors=Nieduszynski IA, Huckerby TN, etal | title = There are two major types of skeletal keratan sulphates | journal = Biochem. J. | year=1990 | volume=271 | issue=1 | pages=243–245 | pmid = 2222415 | pmc = 1149539| doi = 10.1042/bj2710243 }}</ref> The tissue based classification of KS no longer exists as KS types have been shown to be non tissue specific.<ref name=funderburgh/> A third type of KS (KSIII) has also been isolated from brain tissue that is ''O''-linked to specific serine or threonine amino acids via mannose.<ref>{{cite journal | vauthors = Krusius T, Finne J, etal | title = Identification of an O-glycosidic mannose-linked sialylated tetrasaccharide and keratan sulfate oligosaccharides in the chondroitin sulfate proteoglycan of brain | journal = J. Biol. Chem. | date = 25 June 1986 | volume = 261 | issue = 18 | pages = 8237–8242 | doi = 10.1016/S0021-9258(19)83901-7 | doi-access = free | pmid = 2941416 }}</ref>
===Corneal KSI=== The amount of KS found in the cornea is 10 fold higher than it is in cartilage and 2-4 times higher than it is in other tissues.<ref>{{cite journal |author1=Funderburgh JL |author2=Caterson B. |author3=Conrad GW. | title = Distribution of proteoglycans antigenically related to corneal keratan sulfate proteoglycan | journal = J. Biol. Chem. | year=1987 | volume=262 | issue =24 | pages=11634–11640 |doi=10.1016/S0021-9258(18)60856-7 |doi-access=free | pmid = 2957372}}</ref> It is produced by corneal keratocytes<ref name="pmid12933807">{{cite journal |vauthors=Funderburgh JL, Mann MM, Funderburgh ML |title=Keratocyte phenotype mediates proteoglycan structure: a role for fibroblasts in corneal fibrosis |journal=J. Biol. Chem. |volume=278 |issue=46 |pages=45629–37 |date=November 2003 |pmid=12933807 |doi=10.1074/jbc.M303292200 |doi-access=free |pmc=2877919}}</ref> and is thought to play a role of a dynamic buffer of corneal hydration. In a rare progressive disorder called macular corneal dystrophy (MCDC), the synthesis of keratan sulfate is either absent (MCDC type I) or abnormal (MCDC type II).<ref name="OMIM_MCDC">[https://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=217800 Macular dystrophy, corneal, 1]{{dead link|date=July 2025|bot=medic}}{{cbignore|bot=medic}} - OMIM</ref>
===Non-corneal KSI=== Osteoadherin, fibromodulin, and PRELP are core proteins found in bone and cartilage, that are modified by N-linked KS chains. Osteoadherin and Fibromodulin linked KS chains are shorter than those found in the cornea, typically 8-9 disaccharide units in length.<ref>{{cite journal |vauthors=Lauder RM, Huckerby TN, Nieduszynski IA | title = The structure of the keratan sulphate chains attached to fibromodulin from human articular cartilage | journal = Glycoconj. J. | date= 1997| volume= 14 | issue= 5 | pages= 651–660| pmid = 9298700 | doi = 10.1023/A:1018552913584 }}</ref> Whereas corneal KSI is composed of a number of domains showing variable degrees of sulphation the longest of which may be 8-32 disaccharide units in length. The non-reducing terminal of Fibromodulin KS is more similar in structure to the non-reducing terminal of a KSII type keratan sulphate rather than to corneal KSI. KS structure is therefore believed to be determined by the tissue specific availability of glycosyltransferases rather than linkage type to the core protein.<ref name=funderburgh/>
===KSII=== Cartilage KSII is almost entirely sulphated, consisting of disulphated monomers interrupted occasionally by a single monosulphated lactosamine monomer.<ref name=Nieduszynski/> Fucosylation is also common with alpha-linked fucose present at the carbon 3 position of sulphated GlcNAc, except in the case of tracheal KSII where this feature is absent.
==See also== * N-Acetylglucosamine * Galactose * Lumican * Morquio syndrome is marked by the accumulation of KS * Proteoglycan 4
==References== {{Reflist|2}}
==External links== * {{DukeOrtho|Chondroitin_and_keratin_sulfate}} * {{MeshName|Keratan+sulfate}}
{{Glycosaminoglycans}}
{{DEFAULTSORT:Keratan Sulfate}} Category:Glycosaminoglycans Category:Organosulfates