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

sulfated Sulfation (sometimes spelled sulphation in British English) 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 ...

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 acid, uronic sugar and an amino sugar, except i ...

(structural carbohydrates) that have been found especially in the

cornea The cornea is the transparency (optics), transparent front part of the eyeball which covers the Iris (anatomy), iris, pupil, and Anterior chamber of eyeball, anterior chamber. Along with the anterior chamber and Lens (anatomy), lens, the cornea ...

cartilage Cartilage is a resilient and smooth type of connective tissue. Semi-transparent and non-porous, it is usually covered by a tough and fibrous membrane called perichondrium. In tetrapods, it covers and protects the ends of long bones at the joints ...

, and

bone A bone is a rigid organ that constitutes part of the skeleton in most vertebrate animals. Bones protect the various other organs of the body, produce red and white blood cells, store minerals, provide structure and support for the body, ...

. It is also synthesized in the

central nervous system The central nervous system (CNS) is the part of the nervous system consisting primarily of the brain, spinal cord and retina. The CNS is so named because the brain integrates the received information and coordinates and influences the activity o ...

where it participates both in

development Development or developing may refer to: Arts *Development (music), the process by which thematic material is reshaped * Photographic development *Filmmaking, development phase, including finance and budgeting * Development hell, when a proje ...

and in the

glial scar A glial scar formation (gliosis) is a reactive cellular process involving astrogliosis that occurs after injury to the central nervous system. As with scarring in other organs and tissues, the glial scar is the body's mechanism to protect and beg ...

formation following an injury. Keratan sulfates are large, highly hydrated molecules which in joints can act as a cushion to absorb

mechanical shock In mechanics and physics, shock is a sudden acceleration caused, for example, by impact (mechanics), impact, drop, kick, earthquake, or explosion. Shock is a transient physical excitation. Shock describes matter subject to extreme rates of for ...

Structure

Like other

glycosaminoglycan 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 o ...

s keratan sulfate is a linear

polymer A polymer () is a chemical substance, substance or material that consists of very large molecules, or macromolecules, that are constituted by many repeat unit, repeating subunits derived from one or more species of monomers. Due to their br ...

that consists of a repeating

disaccharide A disaccharide (also called a double sugar or ''biose'') is the sugar formed when two monosaccharides are joined by glycosidic linkage. Like monosaccharides, disaccharides are simple sugars soluble in water. Three common examples are sucrose, ...

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 w ...

(PG) in which KS chains are attached to

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

extracellular matrix In biology, the extracellular matrix (ECM), also called intercellular matrix (ICM), is a network consisting of extracellular macromolecules and minerals, such as collagen, enzymes, glycoproteins and hydroxyapatite that provide structural and bio ...

proteins, termed core proteins. KS core proteins include

lumican Lumican, also known as LUM, is an extracellular matrix protein that, in humans, is encoded by the ''LUM'' gene on chromosome 12. Structure Lumican is a proteoglycan Class II member of the small leucine-rich proteoglycan (SLRP) family that incl ...

keratocan Keratocan (KTN) also known as keratan sulfate proteoglycan keratocan, is a protein that in humans is encoded by the ''KERA'' gene. Keratan sulfate proteoglycans (KSPGs) are members of the small leucine-rich proteoglycan (SLRP) family. KSPGs, parti ...

mimecan Osteoglycin (also called mimecan), encoded by the OGN gene, is a human protein. This gene encodes a protein which induces ectopic bone formation in conjunction with transforming growth factor beta. This protein is a small keratan sulfate proteogl ...

, fibromodulin, PRELP, osteoadherin, 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 pr ...

. 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. Chemically, monosaccharides are polyhy ...

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 biosynthe ...

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 Mannose is a sugar with the formula , which sometimes is abbreviated Man. It is one of the monomers of the aldohexose series of carbohydrates. It is a C-2 epimer of glucose. Mannose is important in human metabolism, especially in the glycosylatio ...

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 ''N''-Acetylneuraminic acid (Neu5Ac or NANA) is the predominant sialic acid found in human cells, and many mammalian cells. Other forms, such as N-Glycolylneuraminic acid, may also occur in cells. This residue is negatively charged at physiolog ...

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 The cornea is the transparent front part of the eyeball which covers the iris, pupil, and anterior chamber. Along with the anterior chamber and lens, the cornea refracts light, accounting for approximately two-thirds of the eye's total optical ...

tissue and KSII from

skeletal A skeleton is the structural frame that supports the body of most animals. There are several types of skeletons, including the exoskeleton, which is a rigid outer shell that holds up an organism's shape; the endoskeleton, a rigid internal fram ...

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 Asparagine (symbol Asn or N) is an α-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), an α-carboxylic acid group (which is in the depro ...

amino acid Amino acids are organic compounds that contain both amino and carboxylic acid functional groups. Although over 500 amino acids exist in nature, by far the most important are the 22 α-amino acids incorporated into proteins. Only these 22 a ...

s 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 − ...

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 when dissolved in water), 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 The brain is an organ (biology), organ that serves as the center of the nervous system in all vertebrate and most invertebrate animals. It consists of nervous tissue and is typically located in the head (cephalization), usually near organs for ...

tissue that is ''O''-linked to specific serine or threonine amino acids via

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 keratocyte Corneal keratocytes (corneal fibroblasts) are specialized fibroblasts residing in the corneal stroma, stroma. This corneal layer, representing about 85-90% of corneal thickness, is built up from highly regular collagenous lamellae and extracellular ...

s and is thought to play a role of a dynamic buffer of corneal hydration. In a rare progressive disorder called

macular corneal dystrophy Macular corneal dystrophy, also known as Fehr corneal dystrophy, is a rare pathological condition affecting the stroma of cornea first described by Arthur Groenouw in 1890.Groenouw A. Knötchenförmige Hornhauttrübungen (noduli corneae). Arch Aug ...

(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, fibromodulin, and PRELP are core proteins found in

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

glycosyltransferase Glycosyltransferases (GTFs, Gtfs) are enzymes ( EC 2.4) that establish natural glycosidic linkages. They catalyze the transfer of saccharide moieties from an activated nucleotide sugar (also known as the "glycosyl donor") to a nucleophilic gl ...

s rather than linkage type to the core protein.

KSII

Cartilage Cartilage is a resilient and smooth type of connective tissue. Semi-transparent and non-porous, it is usually covered by a tough and fibrous membrane called perichondrium. In tetrapods, it covers and protects the ends of long bones at the joints ...

KSII is almost entirely sulphated, consisting of disulphated

monomer A monomer ( ; ''mono-'', "one" + '' -mer'', "part") is a molecule that can react together with other monomer molecules to form a larger polymer chain or two- or three-dimensional network in a process called polymerization. Classification Chemis ...

s interrupted occasionally by a single monosulphated lactosamine monomer.

Fucosylation Fucosylation is the process of adding fucose sugar units to a molecule. It is a type of glycosylation. It is important clinically, and high levels of fucosylation have been reported in cancer. In cancer and inflammation there are significant chang ...

is also common with alpha-linked

fucose Fucose is a hexose deoxy sugar with the chemical formula C6H12O5. It is found on ''N''-linked glycans on the mammalian, insect and plant cell surface. Fucose is the fundamental sub-unit of the seaweed polysaccharide fucoidan. The α(1→3) l ...

present at the carbon 3 position of sulphated GlcNAc, except in the case of

tracheal The trachea (: tracheae or tracheas), also known as the windpipe, is a cartilaginous tube that connects the larynx to the bronchi of the lungs, allowing the passage of air, and so is present in almost all animals' lungs. The trachea extends from ...

KSII where this feature is absent.

References

External links

* * {{DEFAULTSORT:Keratan Sulfate Glycosaminoglycans Sulfate esters