Keratan sulfate (KS), also called keratosulfate, is any of several

sulfated Sulfation is the chemical reaction that entails the addition of SO3 group. In principle, many sulfations would involve reactions of sulfur trioxide (SO3). In practice, most sulfations are effected less directly. Regardless of the mechanism, the ...

glycosaminoglycans Glycosaminoglycans (GAGs) or mucopolysaccharides are long, linear polysaccharides consisting of repeating disaccharide units (i.e. two-sugar units). The repeating two-sugar unit consists of a uronic sugar and an amino sugar, except in the case ...

(structural carbohydrates) that have been found especially in the cornea,

cartilage Cartilage is a resilient and smooth type of connective tissue. In tetrapods, it covers and protects the ends of long bones at the joints as articular cartilage, and is a structural component of many body parts including the rib cage, the neck an ...

, and bone. It is also synthesized in the central nervous system where it participates both in development and in the glial scar formation following an injury. Keratan sulfates are large, highly hydrated molecules which in joints can act as a cushion to absorb

mechanical shock A mechanical or physical shock is a sudden acceleration caused, for example, by impact, drop, kick, earthquake, or explosion. Shock is a transient physical excitation. Shock describes matter subject to extreme rates of force with respect to ti ...

Structure

Like other glycosaminoglycans keratan sulfate is a linear polymer that consists of a repeating disaccharide unit. Keratan sulfate occurs as a

proteoglycan Proteoglycans are proteins that are heavily glycosylated. The basic proteoglycan unit consists of a "core protein" with one or more covalently attached glycosaminoglycan (GAG) chain(s). The point of attachment is a serine (Ser) residue to whic ...

(PG) in which KS chains are attached to

cell-surface The cell membrane (also known as the plasma membrane (PM) or cytoplasmic membrane, and historically referred to as the plasmalemma) is a biological membrane that separates and protects the interior of all cells from the outside environment ( ...

or extracellular matrix proteins, termed core proteins. KS core proteins include lumican, keratocan, mimecan, fibromodulin,

PRELP Prolargin is a protein that in humans is encoded by the ''PRELP'' gene. The protein encoded by this gene is a leucine-rich repeat protein present in connective tissue extracellular matrix. This protein functions as a molecule anchoring basemen ...

osteoadherin Osteomodulin (also called osteoadherin or osteoadherin proteoglycan) is a protein that in humans is encoded by the ''OMD'' gene In biology, the word gene (from , ; "... Wilhelm Johannsen coined the word gene to describe the Mendelian units ...

, and

aggrecan Aggrecan (ACAN), also known as cartilage-specific proteoglycan core protein (CSPCP) or chondroitin sulfate proteoglycan 1, is a protein that in humans is encoded by the ''ACAN'' gene. This gene is a member of the lectican (chondroitin sulfate prote ...

. The basic repeating disaccharide unit within keratan sulfate is -3 Galβ1-4 GlcNAc6Sβ1-. This can be sulfated at carbon position 6 (C6) of either or both the Gal or GlcNAc

monosaccharide Monosaccharides (from Greek ''monos'': single, '' sacchar'': sugar), also called simple sugars, are the simplest forms of sugar and the most basic units (monomers) from which all carbohydrates are built. They are usually colorless, water-solub ...

s. However, the detailed

primary structure Protein primary structure is the linear sequence of amino acids in a peptide or protein. By convention, the primary structure of a protein is reported starting from the amino-terminal (N) end to the carboxyl-terminal (C) end. Protein biosynthes ...

of specific KS types are best considered to be composed of three regions: *A linkage region, at one end of which the KS chain is linked to the core protein. *A repeat region, composed of the -3 Galβ1-4 GlcNAcβ1- 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.

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 A skeleton is the structural frame that supports the body of an animal. There are several types of skeletons, including the exoskeleton, which is the stable outer shell of an organism, the endoskeleton, which forms the support structure inside ...

tissue. 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. 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 Serine (symbol Ser or S) is an α-amino acid that is used in the biosynthesis of proteins. It contains an α-amino group (which is in the protonated − form under biological conditions), a carboxyl group (which is in the deprotonated − form un ...

threonine Threonine (symbol Thr or T) is an amino acid that is used in the biosynthesis of proteins. It contains an α-amino group (which is in the protonated −NH form under biological conditions), a carboxyl group (which is in the deprotonated −COO� ...

amino acids via ''N''-acetylgalactosamine. The tissue based classification of KS no longer exists as KS types have been shown to be non tissue specific. 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.

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. It is produced by corneal keratocytes 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).Macular dystrophy, corneal, 1
- OMIM

Non-corneal KSI

Osteoadherin Osteomodulin (also called osteoadherin or osteoadherin proteoglycan) is a protein that in humans is encoded by the ''OMD'' gene In biology, the word gene (from , ; "... Wilhelm Johannsen coined the word gene to describe the Mendelian units ...

, fibromodulin, and

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. 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.

KSII

Cartilage Cartilage is a resilient and smooth type of connective tissue. In tetrapods, it covers and protects the ends of long bones at the joints as articular cartilage, and is a structural component of many body parts including the rib cage, the neck an ...

KSII is almost entirely sulphated, consisting of disulphated monomers interrupted occasionally by a single monosulphated lactosamine monomer. 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.

References

External links

* * {{DEFAULTSORT:Keratan Sulfate Glycosaminoglycans Sulfate esters