Keratan sulfate (KS), also called keratosulfate, is any of several sulfated glycosaminoglycans (structural carbohydrates) that have been found especially in the

cornea The cornea is the transparent front part of the eye that 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 power ...

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 A bone is a Stiffness, rigid Organ (biology), organ that constitutes part of the skeleton in most vertebrate animals. Bones protect the various other organs of the body, produce red blood cell, red and white blood cells, store minerals, provid ...

. 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 and spinal cord. The CNS is so named because the brain integrates the received information and coordinates and influences the activity of all par ...

where it participates both in

development Development or developing may refer to: Arts *Development hell, when a project is stuck in development *Filmmaking, development phase, including finance and budgeting *Development (music), the process thematic material is reshaped * Photograph ...

and in the

glial scar 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 begin ...

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

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 ...

s keratan sulfate is a linear

polymer A polymer (; Greek '' poly-'', "many" + ''-mer'', "part") is a substance or material consisting of very large molecules called macromolecules, composed of many repeating subunits. Due to their broad spectrum of properties, both synthetic a ...

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, la ...

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 ( ...

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

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 inc ...

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, par ...

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 TGF-beta, beta. This protein is a small keratan sulfate ...

fibromodulin Fibromodulin is a protein that in humans is encoded by the ''FMOD'' gene. Fibromodulin is a 42kDa protein of a family of small interstitial leucine-rich repeat proteoglycans (SLRPs). It can have up to four N-linked keratan sulfate chains attach ...

, PRELP,

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. 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

GlcNAc ''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 ...

β1- 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 monomer of the aldohexose series of carbohydrates. It is a C-2 epimer of glucose. Mannose is important in human metabolism, especially in the glycosylation of certain proteins. Several congenital disorders of glycosylation ...

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 eye that 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 powe ...

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 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 hundreds of amino acids exist in nature, by far the most important are the alpha-amino acids, which comprise proteins. Only 22 alpha am ...

s via ''N''-acetylglucosamine and KSII is ''O''-linked to specific serine or

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 A brain is an organ that serves as the center of the nervous system in all vertebrate and most invertebrate animals. It is located in the head, usually close to the sensory organs for senses such as vision. It is the most complex organ in a v ...

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 stroma. This corneal layer, representing about 85-90% of corneal thickness, is built up from highly regular collagenous lamellae and extracellular matrix compone ...

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 named for German ophthalmologist Oskar Fehr (1871-1959), is a rare pathological condition affecting the stroma of cornea. The first signs are usually noticed in the first decade of li ...

(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 ...

, 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 glyco ...

s 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

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

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 chan ...

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) li ...

present at the carbon 3 position of sulphated

, except in the case of

tracheal The trachea, 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 air-breathing animals with lungs. The trachea extends from the la ...

KSII where this feature is absent.

References

External links

* * {{DEFAULTSORT:Keratan Sulfate Glycosaminoglycans Sulfate esters